@misc{GoeldelKamrathMindenetal.2022, author = {G{\"o}ldel, Julia M. and Kamrath, Clemens and Minden, Kirsten and Wiegand, Susanna and Lanzinger, Stefanie and Sengler, Claudia and Weihrauch-Bl{\"u}her, Susann and Holl, Reinhard W. and Tittel, Sascha Ren{\´e} and Warschburger, Petra}, title = {Access to Healthcare for Children and Adolescents with a Chronic Health Condition during the COVID-19 Pandemic: First Results from the KICK-COVID Study in Germany}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {812}, issn = {1866-8364}, doi = {10.25932/publishup-57836}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-578363}, pages = {11}, year = {2022}, abstract = {This study examines the access to healthcare for children and adolescents with three common chronic diseases (type-1 diabetes (T1D), obesity, or juvenile idiopathic arthritis (JIA)) within the 4th (Delta), 5th (Omicron), and beginning of the 6th (Omicron) wave (June 2021 until July 2022) of the COVID-19 pandemic in Germany in a cross-sectional study using three national patient registries. A paper-and-pencil questionnaire was given to parents of pediatric patients (<21 years) during the routine check-ups. The questionnaire contains self-constructed items assessing the frequency of healthcare appointments and cancellations, remote healthcare, and satisfaction with healthcare. In total, 905 parents participated in the T1D-sample, 175 in the obesity-sample, and 786 in the JIA-sample. In general, satisfaction with healthcare (scale: 0-10; 10 reflecting the highest satisfaction) was quite high (median values: T1D 10, JIA 10, obesity 8.5). The proportion of children and adolescents with canceled appointments was relatively small (T1D 14.1\%, JIA 11.1\%, obesity 20\%), with a median of 1 missed appointment, respectively. Only a few parents (T1D 8.6\%; obesity 13.1\%; JIA 5\%) reported obstacles regarding health services during the pandemic. To conclude, it seems that access to healthcare was largely preserved for children and adolescents with chronic health conditions during the COVID-19 pandemic in Germany.}, language = {en} } @article{GoeldelKamrathMindenetal.2022, author = {G{\"o}ldel, Julia M. and Kamrath, Clemens and Minden, Kirsten and Wiegand, Susanna and Lanzinger, Stefanie and Sengler, Claudia and Weihrauch-Bl{\"u}her, Susann and Holl, Reinhard W. and Tittel, Sascha Ren{\´e} and Warschburger, Petra}, title = {Access to Healthcare for Children and Adolescents with a Chronic Health Condition during the COVID-19 Pandemic: First Results from the KICK-COVID Study in Germany}, series = {Children}, volume = {10}, journal = {Children}, edition = {1}, publisher = {MDPI}, address = {Basel, Schweiz}, issn = {2227-9067}, doi = {10.3390/children10010010}, pages = {1 -- 11}, year = {2022}, abstract = {This study examines the access to healthcare for children and adolescents with three common chronic diseases (type-1 diabetes (T1D), obesity, or juvenile idiopathic arthritis (JIA)) within the 4th (Delta), 5th (Omicron), and beginning of the 6th (Omicron) wave (June 2021 until July 2022) of the COVID-19 pandemic in Germany in a cross-sectional study using three national patient registries. A paper-and-pencil questionnaire was given to parents of pediatric patients (<21 years) during the routine check-ups. The questionnaire contains self-constructed items assessing the frequency of healthcare appointments and cancellations, remote healthcare, and satisfaction with healthcare. In total, 905 parents participated in the T1D-sample, 175 in the obesity-sample, and 786 in the JIA-sample. In general, satisfaction with healthcare (scale: 0-10; 10 reflecting the highest satisfaction) was quite high (median values: T1D 10, JIA 10, obesity 8.5). The proportion of children and adolescents with canceled appointments was relatively small (T1D 14.1\%, JIA 11.1\%, obesity 20\%), with a median of 1 missed appointment, respectively. Only a few parents (T1D 8.6\%; obesity 13.1\%; JIA 5\%) reported obstacles regarding health services during the pandemic. To conclude, it seems that access to healthcare was largely preserved for children and adolescents with chronic health conditions during the COVID-19 pandemic in Germany.}, language = {en} } @phdthesis{Polemiti2022, author = {Polemiti, Elli}, title = {Identifying risk of microvascular and macrovascular complications of type 2 diabetes}, doi = {10.25932/publishup-57103}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-571038}, school = {Universit{\"a}t Potsdam}, pages = {xii, 292}, year = {2022}, abstract = {Diabetes is hallmarked by high blood glucose levels, which cause progressive generalised vascular damage, leading to microvascular and macrovascular complications. Diabetes-related complications cause severe and prolonged morbidity and are a major cause of mortality among people with diabetes. Despite increasing attention to risk factors of type 2 diabetes, existing evidence is scarce or inconclusive regarding vascular complications and research investigating both micro- and macrovascular complications is lacking. This thesis aims to contribute to current knowledge by identifying risk factors - mainly related to lifestyle - of vascular complications, addressing methodological limitations of previous literature and providing comparative data between micro- and macrovascular complications. To address this overall aim, three specific objectives were set. The first was to investigate the effects of diabetes complication burden and lifestyle-related risk factors on the incidence of (further) complications. Studies suggest that diabetes complications are interrelated. However, they have been studied mainly independently of individuals' complication burden. A five-state time-to-event model was constructed to examine the longitudinal patterns of micro- (kidney disease, neuropathy and retinopathy) and macrovascular complications (myocardial infarction and stroke) and their association with the occurrence of subsequent complications. Applying the same model, the effect of modifiable lifestyle factors, assessed alone and in combination with complication load, on the incidence of diabetes complications was studied. The selected lifestyle factors were body mass index (BMI), waist circumference, smoking status, physical activity, and intake of coffee, red meat, whole grains, and alcohol. Analyses were conducted in a cohort of 1199 participants with incident type 2 diabetes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, who were free of vascular complications at diabetes diagnosis. During a median follow-up time of 11.6 years, 96 cases of macrovascular complications (myocardial infarction and stroke) and 383 microvascular complications (kidney disease, neuropathy and retinopathy) were identified. In multivariable-adjusted models, the occurrence of a microvascular complication was associated with a higher incidence of further micro- (Hazard ratio [HR] 1.90; 95\% Confidence interval [CI] 0.90, 3.98) and macrovascular complications (HR 4.72; 95\% CI 1.25, 17.68), compared with persons without a complication burden. In addition, participants who developed a macrovascular event had a twofold higher risk of future microvascular complications (HR 2.26; 95\% CI 1.05, 4.86). The models were adjusted for age, sex, state duration, education, lifestyle, glucose-lowering medication, and pre-existing conditions of hypertension and dyslipidaemia. Smoking was positively associated with macrovascular disease, while an inverse association was observed with higher coffee intake. Whole grain and alcohol intake were inversely associated with microvascular complications, and a U-shaped association was observed for red meat intake. BMI and waist circumference were positively associated with microvascular events. The associations between lifestyle factors and incidence of complications were not modified by concurrent complication burden, except for red meat intake and smoking status, where the associations were attenuated among individuals with a previous complication. The second objective was to perform an in-depth investigation of the association between BMI and BMI change and risk of micro- and macrovascular complications. There is an ongoing debate on the association between obesity and risk of macrovascular and microvascular outcomes in type 2 diabetes, with studies suggesting a protective effect among people with overweight or obesity. These findings, however, might be limited due to suboptimal control for smoking, pre-existing chronic disease, or short-follow-up. After additional exclusion of persons with cancer history at diabetes onset, the associations between pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI and incidence of complications were evaluated in multivariable-adjusted Cox models. The analyses were adjusted for age, sex, education, smoking status and duration, physical activity, alcohol consumption, adherence to the Mediterranean diet, and family history of diabetes and cardiovascular disease (CVD). Among 1083 EPIC-Potsdam participants, 85 macrovascular and 347 microvascular complications were identified during a median follow-up period of 10.8 years. Higher pre-diagnosis BMI was associated with an increased risk of total microvascular complications (HR per 5 kg/m2 1.21; 95\% CI 1.07, 1.36), kidney disease (HR 1.39; 95\% CI 1.21, 1.60) and neuropathy (HR 1.12; 95\% CI 0.96, 1.31); but no association was observed for macrovascular complications (HR 1.05; 95\% CI 0.81, 1.36). Effect modification was not evident by sex, smoking status, or age groups. In analyses according to BMI change categories, BMI loss of more than 1\% indicated a decreased risk of total microvascular complications (HR 0.62; 95\% CI 0.47, 0.80), kidney disease (HR 0.57; 95\% CI 0.40, 0.81) and neuropathy (HR 0.73; 95\% CI 0.52, 1.03), compared with participants with a stable BMI. No clear association was observed for macrovascular complications (HR 1.04; 95\% CI 0.62, 1.74). The impact of BMI gain on diabetes-related vascular disease was less evident. Associations were consistent across strata of age, sex, pre-diagnosis BMI, or medication but appeared stronger among never-smokers than current or former smokers. The last objective was to evaluate whether individuals with a high-risk profile for diabetes and cardiovascular disease (CVD) also have a greater risk of complications. Within the EPIC-Potsdam study, two accurate prognostic tools were developed, the German Diabetes Risk Score (GDRS) and the CVD Risk Score (CVDRS), which predict the 5-year type 2 diabetes risk and 10-year CVD risk, respectively. Both scores provide a non-clinical and clinical version. Components of the risk scores include age, sex, waist circumference, prevalence of hypertension, family history of diabetes or CVD, lifestyle factors, and clinical factors (only in clinical versions). The association of the risk scores with diabetes complications and their discriminatory performance for complications were assessed. In crude Cox models, both versions of GDRS and CVDRS were positively associated with macrovascular complications and total microvascular complications, kidney disease and neuropathy. Higher GDRS was also associated with an elevated risk of retinopathy. The discrimination of the scores (clinical and non-clinical) was poor for all complications, with the C-index ranging from 0.58 to 0.66 for macrovascular complications and from 0.60 to 0.62 for microvascular complications. In conclusion, this work illustrates that the risk of complication development among individuals with type 2 diabetes is related to the existing complication load, and attention should be given to regular monitoring for future complications. It underlines the importance of weight management and adherence to healthy lifestyle behaviours, including high intake of whole grains, moderation in red meat and alcohol consumption and avoidance of smoking to prevent major diabetes-associated complications, regardless of complication burden. Risk scores predictive for type 2 diabetes and CVD were related to elevated risks of complications. By optimising several lifestyle and clinical factors, the risk score can be improved and may assist in lowering complication risk.}, language = {en} } @misc{PueschelKlauderHenkelOberlaender, author = {P{\"u}schel, Gerhard Paul and Klauder, Julia and Henkel-Oberl{\"a}nder, Janin}, title = {Macrophages, Low-Grade Inflammation, Insulin Resistance and Hyperinsulinemia: A Mutual Ambiguous Relationship in the Development of Metabolic Diseases}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1279}, issn = {1866-8372}, doi = {10.25932/publishup-57010}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-570106}, pages = {1 -- 30}, abstract = {Metabolic derangement with poor glycemic control accompanying overweight and obesity is associated with chronic low-grade inflammation and hyperinsulinemia. Macrophages, which present a very heterogeneous population of cells, play a key role in the maintenance of normal tissue homeostasis, but functional alterations in the resident macrophage pool as well as newly recruited monocyte-derived macrophages are important drivers in the development of low-grade inflammation. While metabolic dysfunction, insulin resistance and tissue damage may trigger or advance pro-inflammatory responses in macrophages, the inflammation itself contributes to the development of insulin resistance and the resulting hyperinsulinemia. Macrophages express insulin receptors whose downstream signaling networks share a number of knots with the signaling pathways of pattern recognition and cytokine receptors, which shape macrophage polarity. The shared knots allow insulin to enhance or attenuate both pro-inflammatory and anti-inflammatory macrophage responses. This supposedly physiological function may be impaired by hyperinsulinemia or insulin resistance in macrophages. This review discusses the mutual ambiguous relationship of low-grade inflammation, insulin resistance, hyperinsulinemia and the insulin-dependent modulation of macrophage activity with a focus on adipose tissue and liver.}, language = {en} } @article{PueschelKlauderHenkelOberlaender2022, author = {P{\"u}schel, Gerhard and Klauder, Julia and Henkel-Oberl{\"a}nder, Janin}, title = {Macrophages, low-grade inflammation, insulin resistance and hyperinsulinemia}, series = {Journal of Clinical Medicine : open access journal}, volume = {11}, journal = {Journal of Clinical Medicine : open access journal}, number = {15}, publisher = {MDPI}, address = {Basel, Schweiz}, issn = {2077-0383}, doi = {10.3390/jcm11154358}, pages = {1 -- 30}, year = {2022}, abstract = {Metabolic derangement with poor glycemic control accompanying overweight and obesity is associated with chronic low-grade inflammation and hyperinsulinemia. Macrophages, which present a very heterogeneous population of cells, play a key role in the maintenance of normal tissue homeostasis, but functional alterations in the resident macrophage pool as well as newly recruited monocyte-derived macrophages are important drivers in the development of low-grade inflammation. While metabolic dysfunction, insulin resistance and tissue damage may trigger or advance pro-inflammatory responses in macrophages, the inflammation itself contributes to the development of insulin resistance and the resulting hyperinsulinemia. Macrophages express insulin receptors whose downstream signaling networks share a number of knots with the signaling pathways of pattern recognition and cytokine receptors, which shape macrophage polarity. The shared knots allow insulin to enhance or attenuate both pro-inflammatory and anti-inflammatory macrophage responses. This supposedly physiological function may be impaired by hyperinsulinemia or insulin resistance in macrophages. This review discusses the mutual ambiguous relationship of low-grade inflammation, insulin resistance, hyperinsulinemia and the insulin-dependent modulation of macrophage activity with a focus on adipose tissue and liver.}, language = {en} } @phdthesis{Bishop2022, author = {Bishop, Christopher Allen}, title = {Influence of dairy intake on odd-chain fatty acids and energy metabolism}, doi = {10.25932/publishup-56154}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-561541}, school = {Universit{\"a}t Potsdam}, pages = {xii, 104, xv}, year = {2022}, abstract = {As of late, epidemiological studies have highlighted a strong association of dairy intake with lower disease risk, and similarly with an increased amount of odd-chain fatty acids (OCFA). While the OCFA also demonstrate inverse associations with disease incidence, the direct dietary sources and mode of action of the OCFA remain poorly understood. The overall aim of this thesis was to determine the impact of two main fractions of dairy, milk fat and milk protein, on OCFA levels and their influence on health outcomes under high-fat (HF) diet conditions. Both fractions represent viable sources of OCFA, as milk fats contain a significant amount of OCFA and milk proteins are high in branched chain amino acids (BCAA), namely valine (Val) and isoleucine (Ile), which can produce propionyl-CoA (Pr-CoA), a precursor for endogenous OCFA synthesis, while leucine (Leu) does not. Additionally, this project sought to clarify the specific metabolic effects of the OCFA heptadecanoic acid (C17:0). Both short-term and long-term feeding studies were performed using male C57BL/6JRj mice fed HF diets supplemented with milk fat or C17:0, as well as milk protein or individual BCAA (Val; Leu) to determine their influences on OCFA and metabolic health. Short-term feeding revealed that both milk fractions induce OCFA in vivo, and the increases elicited by milk protein could be, in part, explained by Val intake. In vitro studies using primary hepatocytes further showed an induction of OCFA after Val treatment via de novo lipogenesis and increased α-oxidation. In the long-term studies, both milk fat and milk protein increased hepatic and circulating OCFA levels; however, only milk protein elicited protective effects on adiposity and hepatic fat accumulation—likely mediated by the anti-obesogenic effects of an increased Leu intake. In contrast, Val feeding did not increase OCFA levels nor improve obesity, but rather resulted in glucotoxicity-induced insulin resistance in skeletal muscle mediated by its metabolite 3-hydroxyisobutyrate (3-HIB). Finally, while OCFA levels correlated with improved health outcomes, C17:0 produced negligible effects in preventing HF-diet induced health impairments. The results presented herein demonstrate that the beneficial health outcomes associated with dairy intake are likely mediated through the effects of milk protein, while OCFA levels are likely a mere association and do not play a significant causal role in metabolic health under HF conditions. Furthermore, the highly divergent metabolic effects of the two BCAA, Leu and Val, unraveled herein highlight the importance of protein quality.}, language = {en} } @misc{HauffeRathAgyapongetal.2022, author = {Hauffe, Robert and Rath, Michaela and Agyapong, Wilson and Jonas, Wenke and Vogel, Heike and Schulz, Tim Julius and Schwarz, Maria and Kipp, Anna Patricia and Bl{\"u}her, Matthias and Kleinridders, Andr{\´e}}, title = {Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, issn = {1866-8372}, doi = {10.25932/publishup-56170}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-561709}, pages = {1 -- 16}, year = {2022}, abstract = {The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.}, language = {en} } @article{HauffeRathAgyapongetal.2022, author = {Hauffe, Robert and Rath, Michaela and Agyapong, Wilson and Jonas, Wenke and Vogel, Heike and Schulz, Tim Julius and Schwarz, Maria and Kipp, Anna Patricia and Bl{\"u}her, Matthias and Kleinridders, Andr{\´e}}, title = {Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling}, series = {Antioxidants}, volume = {11}, journal = {Antioxidants}, edition = {5}, publisher = {MDPI}, address = {Basel, Schweiz}, issn = {2076-3921}, doi = {10.3390/antiox11050862}, pages = {1 -- 16}, year = {2022}, abstract = {The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.}, language = {en} } @phdthesis{Schell2022, author = {Schell, Mareike}, title = {Investigating the effect of Lactobacillus rhamnosus GG on emotional behavior in diet-induced obese C57BL/6N mice}, school = {Universit{\"a}t Potsdam}, pages = {XVI, 117}, year = {2022}, abstract = {The prevalence of depression and anxiety is increased in obese patients compared to healthy humans, which is partially due to a shared pathogenesis, including insulin resistance and inflammation. These factors are also linked to intestinal dysbiosis. Additionally, the chronic consumption of diets rich in saturated fats results in body weight gain, hormonal resistances and unfavorable changes in the microbiome composition. The intake of Lactobacilli has already been shown to improve dysbiosis along with metabolism and mood. Yet, the beneficial role and the underlying mechanism of Lactobacillus rhamnosus GG (LGG) to improve emotional behavior in established diet-induced obese conditions are, so far, unknown. To characterize the role of LGG in diet-induced obesity, female and male C57BL/6N mice were fed a semi-synthetic low-fat diet (LFD, 10 \% kcal from fat) or a conventional high-fat diet (HFD, 45 \% kcal from fat) for initial 6 weeks, which was followed by daily oral gavage of vehicle or 1x10^8 CFU of LGG until the end of the experiment. Mice were subjected to basic metabolic and extensive behavioral phenotyping, with a focus on emotional behavior. Moreover, composition of cecal gut microbiome, metabolomic profile in plasma and cerebrospinal fluid was investigated and followed by molecular analyses. Both HFD-feeding and LGG application resulted in sex-specific differences. While LGG prevented the increase of plasma insulin, adrenal gland weight and hyperactivity in diet-induced obese female mice, there was no regulation of anxiodepressive-like behavior. In contrast, metabolism of male mice did not benefit from LGG application, but strikingly, LGG decreased specifically depressive-like behavior in the Mousetail Suspension Test which was confirmed by the Splash Test characterizing motivation for 'self-care'. The microbiome analysis in male mice revealed that HFD-feeding, but not LGG application, altered cecal microbiome composition, indicating a direct effect of LGG on behavioral regulation. However, in female mice, both HFD-feeding and LGG application resulted in changes of microbiome composition, which presumably affected metabolism. Moreover, as diet-induced obese female mice unexpectedly did not exhibit anxiodepressive-like behavior, follow-up analyses were conducted in male mice. Here, HFD-feeding significantly altered abundance of plasma lipids whereas LGG decreased branched chain amino acids which associated with improved emotional behavior. In nucleus accumbens (NAcc) and VTA/SN, which belong to the dopaminergic system, LGG restored HFD-induced decrease of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, on gene expression level. Lastly, transcriptome analysis in the NAcc identified gene expression of cholecystokinin as a potential mediator of the effect of LGG on HFD-induced emotional alterations. In summary, this thesis revealed the beneficial effects of LGG application on emotional alterations in established diet-induced obesity. Furthermore, both HFD-feeding and LGG treatment exhibited sex-specific effects, resulting in metabolic improvements in female mice while LGG application mitigated depressive-like behavior in obese male mice along with a molecular signature of restored dopamine synthesis and neuropeptide signaling.}, language = {en} } @article{MummHermanussen2021, author = {Mumm, Rebekka and Hermanussen, Michael}, title = {A short note on the BMI and on secular changes in BMI}, series = {Human biology and public health}, journal = {Human biology and public health}, number = {2}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, issn = {2748-9957}, doi = {10.52905/hbph.v2.17}, year = {2021}, abstract = {Human size changes over time with worldwide secular trends in height, weight, and body mass index (BMI). There is general agreement to relate the state of nutrition to height and weight, and to ratios of weight-to-height. The BMI is a ratio. It is commonly used to classify underweight, overweight and obesity in adults. Yet, the BMI is inappropriate to provide any immediate information on body composition. It is accepted that the BMI is "a simple index to classify underweight, overweight and obesity in adults". It is stated that "policies, programmes and investments need to be "nutrition-sensitive", which means they must have positive impacts on nutrition". It is also stated that "a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions". But these statements are neither warranted by arithmetic considerations, nor by historic evidence. Measuring the BMI is an appropriate screening tool for detecting an unusual weight-to-height ratio, but the BMI is an inappropriate tool for estimating body composition, or suggesting medical and health policy decisions.}, language = {en} } @article{WarschburgerGmeinerMorawietzetal.2018, author = {Warschburger, Petra and Gmeiner, Michaela and Morawietz, Marisa and Rinck, Mike}, title = {Evaluation of an approach-avoidance training intervention for children and adolescents with obesity}, series = {European eating disorders review : the professional journal of the Eating Disorders Associatio}, volume = {26}, journal = {European eating disorders review : the professional journal of the Eating Disorders Associatio}, number = {5}, publisher = {Wiley}, address = {Hoboken}, issn = {1072-4133}, doi = {10.1002/erv.2607}, pages = {472 -- 482}, year = {2018}, abstract = {This study evaluated the efficacy of approach-avoidance training as an additional treatment for children and adolescents with obesity seeking inpatient treatment. Two hundred thirty-two participants (8-16years, 53.9\% girls) were randomly assigned either to multisession approach-avoidance (IG) or to placebo training (CG). As outcomes, cognitive biases post intervention, body mass index, eating behaviour, food intake, self-regulation, and weight-related quality of life were assessed, also at 6- and 12-month follow-up. Modification of approach-avoidance bias was observed, but lacked in transfer over sessions and in generalization to attention and association bias. After 6months, the IG reported less problematic food consumption, higher self-regulation, and higher quality of life; effects did not persist until the 12-month follow-up; no significant interaction effects were observed regarding weight course. Despite there was no direct effect on weight course, approach-avoidance training seems to be associated with promising effects on important pillars for weight loss. Further research concerning clinical effectiveness is warranted.}, language = {en} } @misc{KrsticReinischSchuppetal.2018, author = {Krstic, Jelena and Reinisch, Isabel and Schupp, Michael and Schulz, Tim Julius and Prokesch, Andreas}, title = {p53 functions in adipose tissue metabolism and homeostasis}, series = {International journal of molecular sciences}, volume = {19}, journal = {International journal of molecular sciences}, number = {9}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms19092622}, pages = {21}, year = {2018}, abstract = {As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue-and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53's impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases}, language = {en} } @article{Warschburger2017, author = {Warschburger, Petra}, title = {Jugendliche und junge Erwachsene mit Adipositas}, series = {Die Rehabilitation : Zeitschrift f{\"u}r Praxis und Forschung in der Rehabilitation}, volume = {57}, journal = {Die Rehabilitation : Zeitschrift f{\"u}r Praxis und Forschung in der Rehabilitation}, number = {5}, publisher = {Thieme}, address = {Stuttgart}, issn = {0034-3536}, doi = {10.1055/s-0043-107930}, pages = {295 -- 302}, year = {2017}, abstract = {Hauptziel Adipositas ist eine der Hauptindikationen in der Kinder- und Jugend-Rehabilitation. F{\"u}r {\"a}ltere Jugendliche und junge Erwachsene fehlen altersspezifische Therapieangebote fast vollst{\"a}ndig. Ziel war es die W{\"u}nsche bez{\"u}glich der Inhalte und Methoden einer „perfekten Therapie" im Rahmen eines Rehabilitationsaufenthalts zu untersuchen. Methode Im Rahmen der YOUTH-Studie wurden 147 adip{\"o}se Jugendliche und junge Erwachsene beiderlei Geschlechts (zwischen 15 und 21 Jahren) mithilfe eines standardisierten Fragebogens befragt. Ergebnis Insgesamt zeigten sich relativ wenige alters- und geschlechtsspezifische Unterschiede. Interdisziplin{\"a}r geleitete, koedukative Gruppen mit Elterneinbindung wurden gew{\"u}nscht. Wichtige Themen waren gesunde Ern{\"a}hrung sowie psychosoziale Aspekte. Auch der Pr{\"a}vention von R{\"u}ckf{\"a}llen wurde eine hohe Relevanz zugeschrieben. Schlussfolgerung Psychosoziale Aspekte und die Vorbereitung auf m{\"o}gliche R{\"u}ckfallsituationen sollten integraler Bestandteil der Therapie sein.}, language = {de} } @techreport{MarcusSiedlerZiebarth2021, type = {Working Paper}, author = {Marcus, Jan and Siedler, Thomas and Ziebarth, Nicolas R.}, title = {The Long-Run Effects of Sports Club Vouchers for Primary School Children}, series = {CEPA Discussion Papers}, journal = {CEPA Discussion Papers}, number = {34}, issn = {2628-653X}, doi = {10.25932/publishup-50897}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-508978}, pages = {72}, year = {2021}, abstract = {Starting in 2009, the German state of Saxony distributed sports club membership vouchers among all 33,000 third graders in the state. The policy's objective was to encourage them to develop a long-term habit of exercising. In 2018, we carried out a large register-based survey among several cohorts in Saxony and two neighboring states. Our difference-in-differences estimations show that, even after a decade, awareness of the voucher program was significantly higher in the treatment group. We also find that youth received and redeemed the vouchers. However, we do not find significant short- or long-term effects on sports club membership, physical activity, overweightness, or motor skills.}, language = {en} } @article{CastanoMartinezSchumacherSchumacheretal.2019, author = {Casta{\~n}o Mart{\´i}nez, Mar{\´i}a Teresa and Schumacher, Fabian and Schumacher, Silke and Kochlik, Bastian and Weber, Daniela and Grune, Tilman and Biemann, Ronald and McCann, Adrian and Abraham, Klaus and Weikert, Cornelia and Kleuse, Burkhard and Sch{\"u}rmann, Annette and Laeger, Thomas}, title = {Methionine restriction prevents onset of type 2 diabetes in NZO mice}, series = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology}, volume = {33}, journal = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology}, number = {6}, publisher = {Federation of American Societies for Experimental Biology}, address = {Bethesda}, issn = {0892-6638}, doi = {10.1096/fj.201900150R}, pages = {7092 -- 7102}, year = {2019}, abstract = {Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal\%; carbohydrate, 52 kcal\%; fat, 32 kcal\%) that provided methionine at control (Con; 0.86\% methionine) or low levels (0.17\%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet-induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits via increased circulating levels of FGF21 and merits further investigation.-Castano-Martinez, T., Schumacher, F., Schumacher, S., Kochlik, B., Weber, D., Grune, T., Biemann, R., McCann, A., Abraham, K., Weikert, C., Kleuser, B., Schurmann, A., Laeger, T. Methionine restriction prevents onset of type 2 diabetes in NZO mice.}, language = {en} } @phdthesis{HenkelOberlaender2020, author = {Henkel-Oberl{\"a}nder, Janin}, title = {Einfluss von Prostaglandin E2 auf die Entstehung von Insulinresistenz und die Regulation der Entz{\"u}ndungsantwort bei der Di{\"a}t-induzierten nicht-alkoholischen Fettlebererkrankung}, pages = {171}, year = {2020}, abstract = {Weltweit sind fast 40 \% der Bev{\"o}lkerung {\"u}bergewichtig und die Pr{\"a}valenz von Adipositas, Insulinresistenz und den resultierenden Folgeerkrankungen wie dem Metabolischen Syndrom und Typ-2-Diabetes steigt rapide an. Als h{\"a}ufigste Ursachen werden di{\"a}tetisches Fehlverhalten und mangelnde Bewegung angesehen. Die nicht-alkoholische Fettlebererkrankung (NAFLD), deren Hauptcharakteristikum die exzessive Akkumulation von Lipiden in der Leber ist, korreliert mit dem Body Mass Index (BMI). NAFLD wird als hepatische Manifestation des Metabolischen Syndroms angesehen und ist inzwischen die h{\"a}ufigste Ursache f{\"u}r Leberfunktionsst{\"o}rungen. Die Erkrankung umfasst sowohl die benigne hepatische Steatose (Fettleber) als auch die progressive Form der nicht-alkoholischen Steatohepatitis (NASH), bei der die Steatose von Entz{\"u}ndung und Fibrose begleitet ist. Die Ausbildung einer NASH erh{\"o}ht das Risiko, ein hepatozellul{\"a}res Karzinom (HCC) zu entwickeln und kann zu irreversibler Leberzirrhose und terminalem Organversagen f{\"u}hren. Nahrungsbestandteile wie Cholesterol und Fett-reiche Di{\"a}ten werden als m{\"o}gliche Faktoren diskutiert, die den {\"U}bergang einer einfachen Fettleber zur schweren Verlaufsform der Steatohepatitis / NASH beg{\"u}nstigen. Eine Ausdehnung des Fettgewebes wird von Insulinresistenz und einer niedrig-gradigen chronischen Entz{\"u}ndung des Fettgewebes begleitet. Neben Endotoxinen aus dem Darm gelangen Entz{\"u}ndungsmediatoren aus dem Fettgewebe zur Leber. Als Folge werden residente Makrophagen der Leber, die Kupfferzellen, aktiviert, die eine Entz{\"u}ndungsantwort initiieren und weitere pro-inflammatorische Mediatoren freisetzen, zu denen Chemokine, Cytokine und Prostanoide wie Prostaglandin E2 (PGE2) geh{\"o}ren. In dieser Arbeit soll aufgekl{\"a}rt werden, welchen Beitrag PGE2 an der Ausbildung von Insulinresistenz, hepatischer Steatose und Entz{\"u}ndung im Rahmen von Di{\"a}t-induzierter NASH im komplexen Zusammenspiel mit der Regulation der Cytokin-Produktion und anderen Co-Faktoren wie Hyperinsulin{\"a}mie und Hyperlipid{\"a}mie hat. In murinen und humanen Makrophagen-Populationen wurde untersucht, welche Faktoren die Bildung von PGE2 f{\"o}rdern und wie PGE2 die Entz{\"u}ndungsantwort aktivierter Makrophagen reguliert. In prim{\"a}ren Hepatozyten der Ratte sowie in isolierten humanen Hepatozyten und Zelllinien wurde der Einfluss von PGE2 allein und in Kombination mit Cytokinen, deren Bildung durch PGE2 beeinflusst werden kann, auf die Insulin-abh{\"a}ngige Regulation des Glucose- und Lipid-stoffwechsels untersucht. Um den Einfluss von PGE2 im komplexen Zusammenspiel der Zelltypen in der Leber und im Gesamtorganismus zu erfassen, wurden M{\"a}use, in denen die PGE2-Synthese durch die Deletion der mikrosomalen PGE-Synthase 1 (mPGES1) vermindert war, mit einer NASH-induzierenden Di{\"a}t gef{\"u}ttert. In Lebern von Patienten mit NASH oder in M{\"a}usen mit Di{\"a}t-induzierter NASH war die Expression der PGE2-synthetisierenden Enzyme Cyclooxygenase 2 (COX2) und mPGES1 sowie die Bildung von PGE2 im Vergleich zu gesunden Kontrollen gesteigert und korrelierte mit dem Schweregrad der Lebererkrankung. In prim{\"a}ren Makrophagen aus den Spezies Mensch, Maus und Ratte sowie in humanen Makrophagen-Zelllinien war die Bildung pro-inflammatorischer Mediatoren wie Chemokinen, Cytokinen und Prostaglandinen wie PGE2 verst{\"a}rkt, wenn die Zellen mit Endotoxinen wie Lipopolysaccharid (LPS), Fetts{\"a}uren wie Palmitins{\"a}ure, Cholesterol und Cholesterol-Kristallen oder Insulin, das als Folge der kompensatorischen Hyperinsulin{\"a}mie bei Insulinresistenz verst{\"a}rkt freigesetzt wird, inkubiert wurden. Insulin steigerte dabei synergistisch mit LPS oder Palmitins{\"a}ure die Synthese von PGE2 sowie der anderen Entz{\"u}ndungsmediatoren wie Interleukin (IL) 8 und IL-1β. PGE2 reguliert die Entz{\"u}ndungsantwort: Neben der Induktion der eigenen Synthese-Enzyme verst{\"a}rkte PGE2 die Expression der Immunzell-rekrutierenden Chemokine IL-8 und (C-C-Motiv)-Ligand 2 (CCL2) sowie die der pro-inflammatorischen Cytokine IL-1β und IL-6 in Makrophagen und kann so zur Verst{\"a}rkung der Entz{\"u}ndungsreaktion beitragen. Außerdem f{\"o}rderte PGE2 die Bildung von Oncostatin M (OSM) und OSM induzierte in einer positiven R{\"u}ckkopplungsschleife die Expression der PGE2-synthetisierenden Enzyme. Andererseits hemmte PGE2 die basale und LPS-vermittelte Bildung des potenten pro-inflammatorischen Cytokins Tumornekrosefaktor α (TNFα) und kann so die Entz{\"u}ndungsreaktion abschw{\"a}chen. In prim{\"a}ren Hepatozyten der Ratte und humanen Hepatozyten beeintr{\"a}chtigte PGE2 direkt die Insulin-abh{\"a}ngige Aktivierung der Insulinrezeptor-Signalkette zur Steigerung der Glucose-Verwertung, in dem es durch Signalketten, die den verschiedenen PGE2-Rezeptoren nachgeschaltet sind, Kinasen wie ERK1/2 und IKKβ aktivierte und eine inhibierende Serin-Phosphorylierung der Insulinrezeptorsubstrate bewirkte. PGE2 verst{\"a}rkte außerdem die IL-6- oder OSM-vermittelte Insulinresistenz und Steatose in prim{\"a}ren Hepatozyten der Ratte. Die Wirkung von PGE2 im Gesamtorganismus sollte in M{\"a}usen mit Di{\"a}t-induzierter NASH untersucht werden. Die F{\"u}tterung einer Hochfett-Di{\"a}t mit Schmalz als Fettquelle, das vor allem ges{\"a}ttigte Fetts{\"a}uren enth{\"a}lt, verursachte Fettleibigkeit, Insulinresistenz und eine hepatische Steatose in Wildtyp-M{\"a}usen. In Tieren, die eine Hochfett-Di{\"a}t mit Soja{\"o}l als Fettquelle, das vor allem (ω-6)-mehrfach-unges{\"a}ttigte Fetts{\"a}uren (PUFAs) enth{\"a}lt, oder eine Niedrigfett-Di{\"a}t mit Cholesterol erhielten, war lediglich eine hepatische Steatose nachweisbar, jedoch keine verst{\"a}rkte Gewichtszunahme im Vergleich zu Geschwistertieren, die eine Standard-Di{\"a}t bekamen. Im Gegensatz dazu verursachte die F{\"u}tterung einer Hochfett-Di{\"a}t mit PUFA-reichem Soja{\"o}l als Fettquelle in Kombination mit Cholesterol sowohl Fettleibigkeit und Insulinresistenz als auch hepatische Steatose mit Hepatozyten-Hypertrophie, lobul{\"a}rer Entz{\"u}ndung und beginnender Fibrose in Wildtyp-M{\"a}usen. Diese Tiere spiegelten alle klinischen und histologischen Parameter der humanen NASH im Metabolischen Syndrom wider. Nur die Kombination von hohen Mengen unges{\"a}ttigter Fetts{\"a}uren aus Soja{\"o}l und Cholesterol in der Nahrung f{\"u}hrte zu einer exzessiven Akkumulation des Cholesterols und der Bildung von Cholesterol-Kristallen in den Hepatozyten, die zur Sch{\"a}digung der Mitochondrien, schwerem oxidativem Stress und schließlich zum Absterben der Zellen f{\"u}hrten. Als Konsequenz phagozytieren Kupfferzellen die Zelltr{\"u}mmer der Cholesterol-{\"u}berladenen Hepatozyten, werden dadurch aktiviert, setzen Chemokine, Cytokine und PGE2 frei, die die Entz{\"u}ndungsreaktion verst{\"a}rken und die Infiltration von weiteren Immunzellen initiieren k{\"o}nnen und verursachen so eine Progression zur Steatohepatitis (NASH). Die Deletion der mikrosomalen PGE-Synthase 1 (mPGES1), dem induzierbaren Enzym der PGE2-Synthese aus Cyclooxygenase-abh{\"a}ngigen Vorstufen, reduzierte die Di{\"a}t-abh{\"a}ngige Bildung von PGE2 in der Leber. Die F{\"u}tterung der NASH-induzierenden Di{\"a}t verursachte in Wildtyp- und mPGES1-defizienten M{\"a}usen eine {\"a}hnliche Fettleibigkeit und Zunahme der Fettmasse sowie die Ausbildung von hepatischer Steatose mit Entz{\"u}ndung und Fibrose (NASH) im histologischen Bild. In mPGES1-defizienten M{\"a}usen waren jedoch Parameter f{\"u}r die Infiltration von Entz{\"u}ndungszellen und die Di{\"a}t-abh{\"a}ngige Sch{\"a}digung der Leber im Vergleich zu Wildtyp-Tieren erh{\"o}ht, was sich auch in einer st{\"a}rkeren Di{\"a}t-induzierten systemischen Insulinresistenz widerspiegelte. Die Bildung des pro-inflammatorischen und pro-apoptotischen Cytokins TNFα war in mPGES1-defizienten M{\"a}usen durch die Aufhebung der negativen R{\"u}ckkopplungshemmung verst{\"a}rkt, was einen gesteigerten Di{\"a}t-induzierten Zelluntergang gestresster Lipid-{\"u}berladener Hepatozyten und eine nach-geschaltete Entz{\"u}ndungsantwort zur Folge hatte. Zusammenfassend wurde unter den gew{\"a}hlten Versuchsbedingungen in vivo eine anti-inflammatorische Rolle von PGE2 verifiziert, da das Prostanoid vor allem indirekt durch die Hemmung der TNFα-vermittelten Entz{\"u}ndungsreaktion die Sch{\"a}digung der Leber, die Verst{\"a}rkung der Entz{\"u}ndung und die Ausbildung von Insulinresistenz im Rahmen der Di{\"a}t-abh{\"a}ngigen Fettlebererkrankung abschw{\"a}chte.}, language = {de} } @misc{KrsticReinischSchuppetal.2018, author = {Krstic, Jelena and Reinisch, Isabel and Schupp, Michael and Schulz, Tim Julius and Prokesch, Andreas}, title = {p53 functions in adipose tissue metabolism and homeostasis}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1047}, issn = {1866-8372}, doi = {10.25932/publishup-46906}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-469069}, pages = {21}, year = {2018}, abstract = {As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue-and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53's impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases.}, language = {en} } @article{JohnGruneOttetal.2018, author = {John, Cathleen and Grune, Jana and Ott, Christiane and Nowotny, Kerstin and Deubel, Stefanie and K{\"u}hne, Arne and Schubert, Carola and Kintscher, Ulrich and Regitz-Zagrosek, Vera and Grune, Tilman}, title = {Sex Differences in Cardiac Mitochondria in the New Zealand Obese Mouse}, series = {Frontiers in Endocrinology}, volume = {9}, journal = {Frontiers in Endocrinology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-2392}, doi = {10.3389/fendo.2018.00732}, pages = {9}, year = {2018}, abstract = {Background: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function. Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model. Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, the mitochondrial function only in male NZO hearts was significantly reduced and ERK1/2 and AMPK protein levels were altered. Conclusions: This is the first report demonstrating that the cardiac phenotype in male diabetic NZO mice is associated with impaired cardiac energy function and signaling events.}, language = {en} } @article{WarschburgerZitzmann2019, author = {Warschburger, Petra and Zitzmann, Jana}, title = {Does an Age-Specific Treatment Program Augment the Efficacy of a Cognitive-Behavioral Weight Loss Program in Adolescence and Young Adulthood?}, series = {Nutrients}, volume = {2019}, journal = {Nutrients}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu11092053}, pages = {18}, year = {2019}, abstract = {Research on weight-loss interventions in emerging adulthood is warranted. Therefore, a cognitive-behavioral group treatment (CBT), including development-specific topics for adolescents and young adults with obesity (YOUTH), was developed. In a controlled study, we compared the efficacy of this age-specific CBT group intervention to an age-unspecific CBT group delivered across ages in an inpatient setting. The primary outcome was body mass index standard deviation score (BMI-SDS) over the course of one year; secondary outcomes were health-related and disease-specific quality of life (QoL). 266 participants aged 16 to 21 years (65\% females) were randomized. Intention-to-treat (ITT) and per-protocol analyses (PPA) were performed. For both group interventions, we observed significant and clinically relevant improvements in BMI-SDS and QoL over the course of time with small to large effect sizes. Contrary to our hypothesis, the age-specific intervention was not superior to the age-unspecific CBT-approach.}, language = {en} } @misc{WarschburgerZitzmann2019, author = {Warschburger, Petra and Zitzmann, Jana}, title = {Does an Age-Specific Treatment Program Augment the Efficacy of a Cognitive-Behavioral Weight Loss Program in Adolescence and Young Adulthood? Results from a Controlled Study}, series = {Postprints der Universit{\"a}t Potsdam Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam Humanwissenschaftliche Reihe}, number = {584}, issn = {1866-8364}, doi = {10.25932/publishup-43942}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-439424}, pages = {20}, year = {2019}, abstract = {Research on weight-loss interventions in emerging adulthood is warranted. Therefore, a cognitive-behavioral group treatment (CBT), including development-specific topics for adolescents and young adults with obesity (YOUTH), was developed. In a controlled study, we compared the efficacy of this age-specific CBT group intervention to an age-unspecific CBT group delivered across ages in an inpatient setting. The primary outcome was body mass index standard deviation score (BMI-SDS) over the course of one year; secondary outcomes were health-related and disease-specific quality of life (QoL). 266 participants aged 16 to 21 years (65\% females) were randomized. Intention-to-treat (ITT) and per-protocol analyses (PPA) were performed. For both group interventions, we observed significant and clinically relevant improvements in BMI-SDS and QoL over the course of time with small to large effect sizes. Contrary to our hypothesis, the age-specific intervention was not superior to the age-unspecific CBT-approach.}, language = {en} } @misc{Blaut2015, author = {Blaut, Michael}, title = {Gut microbiota and energy balance}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, number = {602}, issn = {1866-8372}, doi = {10.25932/publishup-41446}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-414462}, pages = {227 -- 234}, year = {2015}, abstract = {The microbial community populating the human digestive tract has been linked to the development of obesity, diabetes and liver diseases. Proposed mechanisms on how the gut microbiota could contribute to obesity and metabolic diseases include: (1) improved energy extraction from diet by the conversion of dietary fibre to SCFA; (2) increased intestinal permeability for bacterial lipopolysaccharides (LPS) in response to the consumption of high-fat diets resulting in an elevated systemic LPS level and low-grade inflammation. Animal studies indicate differences in the physiologic effects of fermentable and non-fermentable dietary fibres as well as differences in long-and short-term effects of fermentable dietary fibre. The human intestinal microbiome is enriched in genes involved in the degradation of indigestible polysaccharides. The extent to which dietary fibres are fermented and in which molar ratio SCFA are formed depends on their physicochemical properties and on the individual microbiome. Acetate and propionate play an important role in lipid and glucose metabolism. Acetate serves as a substrate for de novo lipogenesis in liver, whereas propionate can be utilised for gluconeogenesis. The conversion of fermentable dietary fibre to SCFA provides additional energy to the host which could promote obesity. However, epidemiologic studies indicate that diets rich in fibre rather prevent than promote obesity development. This may be due to the fact that SCFA are also ligands of free fatty acid receptors (FFAR). Activation of FFAR leads to an increased expression and secretion of enteroendocrine hormones such as glucagon-like-peptide 1 or peptide YY which cause satiety. In conclusion, the role of SCFA in host energy balance needs to be re-evaluated.}, language = {en} } @misc{SadowskaHausmannWuertzKozak2018, author = {Sadowska, Aleksandra and Hausmann, Oliver Nic and Wuertz-Kozak, Karin}, title = {Inflammaging in the intervertebral disc}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, number = {519}, doi = {10.25932/publishup-41408}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-414081}, pages = {9}, year = {2018}, abstract = {Degeneration of the intervertebral disc - triggered by ageing, mechanical stress, traumatic injury, infection, inflammation and other factors - has a significant role in the development of low back pain. Back pain not only has a high prevalence, but also a major socio-economic impact. With the ageing population, its occurrence and costs are expected to grow even more in the future. Disc degeneration is characterized by matrix breakdown, loss in proteoglycans and thus water content, disc height loss and an increase in inflammatory molecules. The accumulation of cytokines, such as interleukin (IL)-1 , IL-8 or tumor necrosis factor (TNF)-, together with age-related immune deficiency, leads to the so-called inflammaging - low-grade, chronic inflammation with a crucial role in pain development. Despite the relevance of these molecular processes, current therapies target symptoms, but not underlying causes. This review describes the biological and biomechanical changes that occur in a degenerated disc, discusses the connection between disc degeneration and inflammaging, highlights factors that enhance the inflammatory processes in disc pathologies and suggests future research avenues.}, language = {en} } @phdthesis{Leupelt2017, author = {Leupelt, Anke Verena}, title = {Hormonelle K{\"o}rpergewichtsregulation nach Gewichtsreduktion im Rahmen der multimodalen randomisierten Interventionsstudie MAINTAIN}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-413181}, school = {Universit{\"a}t Potsdam}, pages = {XIII, 104}, year = {2017}, abstract = {Adipositas wird mit einer Vielzahl schwerwiegender Folgeerkrankungen in Verbindung gebracht. Eine Gewichtsreduktion f{\"u}hrt zu einer Verbesserung der metabolischen Folgen der Adipositas. Es ist bekannt, dass die Mehrzahl der adip{\"o}sen Personen in den Monaten nach der Gewichtsreduktion einen Großteil des abgenommenen Gewichts wieder zunimmt. Nichtsdestotrotz existiert eine hohe Variabilit{\"a}t hinsichtlich des Langzeiterfolges einer Gewichtsreduktion. Der erfolgreiche Erhalt des reduzierten K{\"o}rpergewichts einiger Personen f{\"u}hrt zu der Frage nach den Faktoren, die einen Gewichtserhalt beeinflussen, mit dem Ziel einen Ansatzpunkt f{\"u}r m{\"o}gliche Therapiestrategien zu identifizieren. In der vorliegenden Arbeit wurde im Rahmen einer kontrollierten, randomisierten Studie mit 143 {\"u}bergewichtigen Probanden untersucht, ob nach einer dreimonatigen Gewichtsreduktion eine zw{\"o}lfmonatige gewichtsstabilisierende Lebensstilintervention einen Einfluss auf die Ver{\"a}nderungen der neuroendokrinen Regelkreisl{\"a}ufe und damit auf den langfristigen Gewichtserhalt {\"u}ber einen Zeitraum von achtzehn Monaten hat. Hierbei wurde im Vergleich der beiden Behandlungsgruppen prim{\"a}r festgestellt, dass die multimodale Lebensstilintervention zu einer Gewichtstabilisierung {\"u}ber die Dauer dieser zw{\"o}lfmonatigen Behandlungsphase f{\"u}hrte. In der Kontrollgruppe kam es zu einer moderaten Gewichtszunahme . Dadurch war nach Beendigung der Interventionsphase der BMI der Teilnehmer in der Kontrollgruppe h{\"o}her als der in der Interventionsgruppe (34,1±6,0 kg*m-2 vs. 32,4±5,7 kg*m-2; p<0,01). W{\"a}hrend der Nachbeobachtungszeit war die Interventionsgruppe durch eine signifikant st{\"a}rkere Gewichtswiederzunahme im Vergleich zur Kontrollgruppe gekennzeichnet, so dass der BMI zwischen beiden Behandlungsgruppen bereits sechs Monate nach der Intervention keinen Unterschied mehr aufwies. Bez{\"u}glich der hormonellen Ver{\"a}nderung durch die Gewichtsreduktion wurde, wie erwartet, eine Auslenkung des endokrinen Systems beobachtet. Jedoch konnte kein Unterschied der untersuchten Hormone im Vergleich der beiden Behandlungsgruppen ausfindig gemacht werden. Im Verlauf der Gewichtsabnahme und der anschließenden Studienphasen zeigten sich tendenziell drei verschiedene Verlaufsmuster in den hormonellen Ver{\"a}nderungen. Nach einer zus{\"a}tzlichen Adjustierung auf den jeweiligen BMI des Untersuchungszeitpunktes konnte f{\"u}r die TSH-Spiegel (p<0,05), die Schilddr{\"u}senhormone (p<0,001) und f{\"u}r die IGF 1-Spiegel (p<0,001) eine {\"u}ber die Studienzeit anhaltende Ver{\"a}nderung festgestellt werden. Abschließend wurde behandlungsgruppenunabh{\"a}ngig untersucht, ob die Hormonspiegel nach Gewichtsreduktion oder ob die relative hormonelle Ver{\"a}nderung w{\"a}hrend der Gewichtsreduktion pr{\"a}diktiv f{\"u}r den Erfolg der Gewichterhaltungsphase ist. Hier fand sich f{\"u}r die Mehrzahl der hormonellen Parameter kein Effekt auf die Langzeitentwicklung der Gewichtszunahme. Jedoch konnte gezeigt werden, dass eine geringere Abnahme der 24h Urin-Metanephrin-Ausscheidung w{\"a}hrend der Gewichtsabnahmephase mit einem besseren Erfolg bez{\"u}glich des Gewichtserhalts {\"u}ber die achtzehnmonatige Studienzeit assoziiert war (standardisiertes Beta= -0,365; r2=0,133 p<0,01). Die anderen hormonellen Achsen zeigten keinen nachweislichen Effekt.}, language = {de} } @misc{WotingBlaut2016, author = {Woting, Anni and Blaut, Michael}, title = {The intestinal microbiota in metabolic disease}, series = {Nutrients}, journal = {Nutrients}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407687}, pages = {19}, year = {2016}, abstract = {Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions.}, language = {en} } @phdthesis{Kasch2017, author = {Kasch, Juliane}, title = {Impact of maternal high-fat consumption on offspring exercise performance, skeletal muscle energy metabolism, and obesity susceptibility}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-409703}, school = {Universit{\"a}t Potsdam}, pages = {XII, 95, XXV}, year = {2017}, abstract = {Background: Obesity is thought to be the consequence of an unhealthy nutrition and a lack of physical activity. Although the resulting metabolic alterations such as impaired glucose homeostasis and insulin sensitivity can usually be improved by physical activity, some obese patients fail to enhance skeletal muscle metabolic health with exercise training. Since this might be largely heritable, maternal nutrition during pregnancy and lactation is hypothesized to impair offspring skeletal muscle physiology. Objectives: This PhD thesis aims to investigate the consequences of maternal high-fat diet (mHFD) consumption on offspring skeletal muscle physiology and exercise performance. We could show that maternal high-fat diet during gestation and lactation decreases the offspring's training efficiency and endurance performance by influencing the epigenetic profile of their skeletal muscle and altering the adaptation to an acute exercise bout, which in long-term, increases offspring obesity susceptibility. Experimental setup: To investigate this issue in detail, we conducted several studies with a similar maternal feeding regime. Dams (C57BL/6J) were either fed a low-fat diet (LFD; 10 energy\% from fat) or high-fat diet (HFD; 40 energy\% from fat) during pregnancy and lactation. After weaning, male offspring of both maternal groups were switched to a LFD, on which they remained until sacrifice in week 6, 15 or 25. In one study, LFD feeding was followed by HFD provision from week 15 until week 25 to elucidate the effects on offspring obesity susceptibility. In week 7, all mice were randomly allocated to a sedentary group (without running wheel) or an exercised group (with running wheel for voluntary exercise training). Additionally, treadmill endurance tests were conducted to investigate training performance and efficiency. In order to uncover regulatory mechanisms, each study was combined with a specific analytical setup, such as whole genome microarray analysis, gene and protein expression analysis, DNA methylation analyses, and enzyme activity assays. Results: mHFD offspring displayed a reduced training efficiency and endurance capacity. This was not due to an altered skeletal muscle phenotype with changes in fiber size, number, and type. DNA methylation measurements in 6 week old offspring showed a hypomethylation of the Nr4a1 gene in mHFD offspring leading to an increased gene expression. Since Nr4a1 plays an important role in the regulation of skeletal muscle energy metabolism and early exercise adaptation, this could affect offspring training efficiency and exercise performance in later life. Investigation of the acute response to exercise showed that mHFD offspring displayed a reduced gene expression of vascularization markers (Hif1a, Vegfb, etc) pointing towards a reduced angiogenesis which could possibly contribute to their reduced endurance capacity. Furthermore, an impaired glucose utilization of skeletal muscle during the acute exercise bout by an impaired skeletal muscle glucose handling was evidenced by higher blood glucose levels, lower GLUT4 translocation and diminished Lactate dehydrogenase activity in mHFD offspring immediately after the endurance test. These points towards a disturbed use of glucose as a substrate during endurance exercise. Prolonged HFD feeding during adulthood increases offspring fat mass gain in mHFD offspring compared to offspring from low-fat fed mothers and also reduces their insulin sensitivity pointing towards a higher obesity and diabetes susceptibility despite exercise training. Consequently, mHFD reduces offspring responsiveness to the beneficial effects of voluntary exercise training. Conclusion: The results of this PhD thesis demonstrate that mHFD consumption impairs the offspring's training efficiency and endurance capacity, and reduced the beneficial effects of exercise on the development of diet-induced obesity and insulin resistance in the offspring. This might be due to changes in skeletal muscle epigenetic profile and/or an impaired skeletal muscle angiogenesis and glucose utilization during an acute exercise bout, which could contribute to a disturbed adaptive response to exercise training.}, language = {en} } @misc{Warschburger2017, author = {Warschburger, Petra}, title = {SRT-Joy - computer-assisted self-regulation training for obese children and adolescents: study protocol for a randomized controlled trial}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-401793}, pages = {10}, year = {2017}, abstract = {Background: Obesity is not only a highly prevalent disease but also poses a considerable burden on children and their families. Evidence is increasing that a lack of self-regulation skills may play a role in the etiology and maintenance of obesity. Our goal with this currently ongoing trial is to examine whether training that focuses on the enhancement of self-regulation skills may increase the sustainability of a complex lifestyle intervention. Methods/Design: In a multicenter, prospective, parallel group, randomized controlled superiority trial, 226 obese children and adolescents aged 8 to 16 years will be allocated either to a newly developed computer-training program to improve their self-regulation abilities or to a placebo control group. Randomization occurs centrally and blockwise at a 1:1 allocation ratio for each center. This study is performed in pediatric inpatient rehabilitation facilities specialized in the treatment of obesity. Observer-blind assessments of outcome variables take place at four times: at the beginning of the rehabilitation (pre), at the end of the training in the rehabilitation (post), and 6 and 12 months post-rehabilitation intervention. The primary outcome is the course of BMI-SDS over 1 year after the end of the inpatient rehabilitation. Secondary endpoints are the self-regulation skills. In addition, health-related quality of life, and snack intake will be analyzed. Discussion: The computer-based training programs might be a feasible and attractive tool to increase the sustainability of the weight loss reached during inpatient rehabilitation.}, language = {en} } @misc{WarschburgerKroeller2017, author = {Warschburger, Petra and Kr{\"o}ller, Katja}, title = {Childhood overweight and obesity}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-400954}, pages = {8}, year = {2017}, abstract = {Background: There is an increasing awareness of the impact of parental risk perception on the weight course of the child and the parent's readiness to engage in preventive efforts, but only less is known about factors related to the parental perception of the right time for the implementation of preventive activities. The aim of this study was to examine parental perceptions of the appropriate time to engage in child weight management strategies, and the factors associated with different weight points at which mothers recognize the need for preventive actions. Methods: 352 mothers with children aged 2-10 years took part in the study. We assessed mothers' perceptions of the actual and preferred weight status of their child, their ability to identify overweight and knowledge of its associated health risks, as well as perceptions of the right time for action to prevent overweight in their child. A regression analysis was conducted to examine whether demographic and weight related factors as well as the maternal general risk perception were associated with recognizing the need to implement prevention strategies. Results: Although most of the parents considered a BMI in the 75th to 90th percentile a valid reason to engage in the prevention of overweight, 19\% of the mothers were not willing to engage in prevention until their child reached the 97th percentile. Whereas the child's sex and the identification of an elevated BMI were significant predictors for parents' recognition of the 75th percentile as right point to engage in prevention efforts, an inability to recognize physical health risks associated with overweight silhouettes emerged as a significant factor predicting which parents would delay prevention efforts until a child's BMI reached the 97th percentile. Conclusion: Parental misperceptions of overweight and associated health risks constitute unfavorable conditions for preventive actions. Feedback on the health risks associated with overweight could help increase maternal readiness for change.}, language = {en} } @article{JoppSchefflerHermanussen2014, author = {Jopp, Eilin and Scheffler, Christiane and Hermanussen, Michael}, title = {Prevention and anthropology}, series = {Journal of biological and clinical anthropology : Anthropologischer Anzeiger ; Mitteilungsorgan der Gesellschaft f{\"u}r Anthropologie}, volume = {71}, journal = {Journal of biological and clinical anthropology : Anthropologischer Anzeiger ; Mitteilungsorgan der Gesellschaft f{\"u}r Anthropologie}, number = {1-2}, publisher = {Schweizerbart}, address = {Stuttgart}, issn = {0003-5548}, doi = {10.1127/0003-5548/2014/0384}, pages = {135 -- 141}, year = {2014}, abstract = {Screening is an important issue in medicine and is used to early identify unrecognised diseases in persons who are apparently in good health. Screening strongly relies on the concept of "normal values". Normal values are defined as values that are frequently observed in a population and usually range within certain statistical limits. Screening for obesity should start early as the prevalence of obesity consolidates already at early school age. Though widely practiced, measuring BMI is not the ultimate solution for detecting obesity. Children with high BMI may be "robust" in skeletal dimensions. Assessing skeletal robustness and in particularly assessing developmental tempo in adolescents are also important issues in health screening. Yet, in spite of the necessity of screening investigations, appropriate reference values are often missing. Meanwhile, new concepts of growth diagrams have been developed. Stage line diagrams are useful for tracking developmental processes over time. Functional data analyses have efficiently been used for analysing longitudinal growth in height and assessing the tempo of maturation. Convenient low-cost statistics have also been developed for generating synthetic national references.}, language = {en} } @article{KroellerWarschburger2011, author = {Kroeller, Katja and Warschburger, Petra}, title = {Problematic eating behavior in childhood do maternal feeding patterns play a role?}, series = {Praxis der Kinderpsychologie und Kinderpsychiatrie : Ergebnisse aus Psychotherapie, Beratung und Psychiatrie}, volume = {60}, journal = {Praxis der Kinderpsychologie und Kinderpsychiatrie : Ergebnisse aus Psychotherapie, Beratung und Psychiatrie}, number = {4}, publisher = {Vandenhoeck \& Ruprecht}, address = {G{\"o}ttingen}, issn = {0032-7034}, pages = {253 -- 269}, year = {2011}, abstract = {Past research indicates an association in adults and young people of emotional and contextual factors with a higher risk for the development of eating disorders or obesity. Few studies focus on problematic eating patterns in childhood, especially in association with parental feeding strategies. 482 mothers completed a questionnaire about eating behaviors and the weight status of their 1- to 10-year-old child as well as their own feeding strategies. A classification of the child's eating behavior (food responsiveness, emotional eating, external eating, eating time and meal structure) using hierarchical cluster analysis revealed a conspicuous eating pattern (10 \%) showing above-average values in all eating behaviors. Controlling for weight and demographic variables mothers of children with conspicuous eating patterns were characterized by restrictive strategies and were less likely to encourage or facilitate their child to control his or her eating. Similar problematic eating patterns were also identified in early childhood. The association of maternal feeding strategies - beyond weight control issues - with conspicuous eating patterns in children might indicate a possibility of early prevention through parent training.}, language = {de} } @article{SunHuangMengetal.2012, author = {Sun, Sheng-Yun and Huang, Jin and Meng, Min-Jie and Lu, Jia-Hai and Hocher, Berthold and Liu, Kang-Li and Yang, Qin-He and Zhu, Xiao-Feng}, title = {Improvement of lipid profile and reduction of body weight by Shan He Jian Fei Granules in high fat diet-induced obese rats}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {1-2}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, pages = {81 -- 87}, year = {2012}, abstract = {Background: The goal was to study lipid profiles (TG, TC, LDL, HDL), effects on serum leptin, and fat tissue adiponectin, and resistin as well as body weight effects of Shan He Jian Fei Granules (SHJFG) in rats on a high fat diet. Methods: Rats were randomly divided into five groups: normal control group fed with normal fat diet, rats on high fat diet receiving low dosage, middle dosage, high dosage of Shan He Jian Fei Granules (SHJFG) as well as a high fat diet group receiving placebo. Rats were treated for 8 weeks. Body weight and naso-anal length of each rat were recorded and Lee's index was calculated. Serum TG, TC, LDL, HDL and leptin concentrations were analyzed. The gene expressions of adiponectin and resistin in adipose tissues were tested by RT-PCR. Results: Compared to the high-fat diet group, body weights, Lee's indexes, weight of fat tissues and serum TG, TC, LDL and leptin of SHJFG groups significantly decreased (p<0.05), whereas mRNA expressions of adiponectin and resistin of SHJFG groups significantly increased (p<0.05). Conclusions: SHJFG could significantly lower body weight and serum TG, TC, and LDL of obese rats. The effects of SHJFG in lowering leptin synthesis and raising mRNA expression of adiponectin and resistin in fat tissues may act as part of the mechanisms in lowering body weight of obese rats. Further studies are needed to demonstrate whether SHJFG may also reduce overall cardiovascular morbidity and mortality like other lipid lowering drugs.}, language = {en} } @article{VickersCheethamBirminghametal.2012, author = {Vickers, Steven P. and Cheetham, Sharon C. and Birmingham, Gareth D. and Rowley, Helen L. and Headland, Katie R. and Dickinson, Keith and Grempler, Rolf and Hocher, Berthold and Mark, Michael and Klein, Thomas}, title = {Effects of the DPP-4 Inhibitor, Linagliptin, in Diet-Induced obese rats a comparison in Naive and Exenatide-Treated Animals}, series = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, volume = {58}, journal = {Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion}, number = {7-8}, publisher = {Clin Lab Publ., Verl. Klinisches Labor}, address = {Heidelberg}, issn = {1433-6510}, doi = {10.7754/Clin.Lab.2011.110919}, pages = {787 -- 799}, year = {2012}, abstract = {Background: To assess the chronic effect of the DPP-4 inhibitor, linagliptin, alone, in combination with exenatide, and during exenatide withdrawal, in diet-induced obese (DIO) rats. Methods: Female Wistar rats were exposed to a cafeteria diet to induce obesity. Animals were then dosed with vehicle or linagliptin (3 mg/kg PO) orally once-daily for a 28 day period. In a subsequent study, rats received exenatide (either 3 or 30 mu g/kg/day) or vehicle by osmotic mini-pump for 28 days. In addition, groups of animals were dosed orally with linagliptin either alone or in combination with a 3 mu g/kg/day exenatide dose for the study duration. In a final study, rats were administered exenatide (30 mu g/kg/day) or vehicle by osmotic mini-pump for eleven days. Subsequently, exenatide-treated animals were transferred to vehicle or continued exenatide infusion for a further ten days. Animals transferred from exenatide to vehicle were also dosed orally with either vehicle or linagliptin. In all studies, body weight, food and water intake were recorded daily and relevant plasma parameters and carcass composition were determined. Results: In contrast to exenatide, linagliptin did not significantly reduce body weight or carcass fat in DIO rats versus controls. Linagliptin augmented the effect of exenatide to reduce body fat when given in combination but did not affect the body weight response. In rats withdrawn from exenatide, weight regain was observed such that body weight was not significantly different to controls. Linagliptin reduced weight regain after withdrawal of exenatide such that a significant difference from controls was evident. Conclusions: These data demonstrate that linagliptin does not significantly alter body weight in either untreated or exenatide-treated DIO rats, although it delays weight gain after exenatide withdrawal. This finding may suggest the utility of DPP-4 inhibitors in reducing body weight during periods of weight gain.}, language = {en} } @phdthesis{Brachs2015, author = {Brachs, Maria}, title = {Genome wide expression analysis and metabolic mechanisms predicting body weight maintenance}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-100767}, school = {Universit{\"a}t Potsdam}, pages = {106}, year = {2015}, abstract = {Obesity is a major health problem for many developing and industrial countries. Increasing rates reach almost 50 \% of the population in some countries and related metabolic diseases including cardiovascular events and T2DM are challenging the health systems. Adiposity, an increase in body fat mass, is a major hallmark of obesity. Adipose tissue is long known not only to store lipids but also to influence whole-body metabolism including food intake, energy expenditure and insulin sensitivity. Adipocytes can store lipids and thereby protect other tissue from lipotoxic damage. However, if the energy intake is higher than the energy expenditure over a sustained time period, adipose tissue will expand. This can lead to an impaired adipose tissue function resulting in higher levels of plasma lipids, which can affect other tissue like skeletal muscle, finally leading to metabolic complications. Several studies showed beneficial metabolic effects of weight reduction in obese subjects immediately after weight loss. However, weight regain is frequently observed along with potential negative effects on cardiovascular risk factors and a high intra-individual response. We performed a body weight maintenance study investigating the mechanisms of weight maintenance after intended WR. Therefore we used a low caloric diet followed by a 12-month life-style intervention. Comprehensive phenotyping including fat and muscle biopsies was conducted to investigate hormonal as well as metabolic influences on body weight regulation. In this study, we showed that weight reduction has numerous potentially beneficial effects on metabolic parameters. After 3-month WR subjects showed significant weight and fat mass reduction, lower TG levels as well as higher insulin sensitivity. Using RNA-Seq to analyse whole fat and muscle transcriptome a strong impact of weight reduction on adipose tissue gene expression was observed. Gene expression alterations over weight reduction included several cellular metabolic genes involved in lipid and glucose metabolism as well as insulin signalling and regulatory pathways. These changes were also associated with anthropometric parameters assigning body composition. Our data indicated that weight reduction leads to a decreased expression of several lipid catabolic as well as anabolic genes. Long-term body weight maintenance might be influenced by several parameters including hormones, metabolic intermediates as well as the transcriptional landscape of metabolic active tissues. Our data showed that genes involved in biosynthesis of unsaturated fatty acids might influence the BMI 18-month after a weight reduction phase. This was further supported by analysing metabolic parameters including RQ and FFA levels. We could show that subjects maintaining their lost body weight had a higher RQ and lower FFA levels, indicating increased metabolic flexibility in subjects. Using this transcriptomic approach we hypothesize that low expression levels of lipid synthetic genes in adipose tissue together with a higher mitochondrial activity in skeletal muscle tissue might be beneficial in terms of body weight maintenance.}, language = {en} } @phdthesis{Doering2013, author = {D{\"o}ring, Ivonne}, title = {Subjektive Krankheitskonzepte adip{\"o}ser Kinder : ihre Erfassung und ihr Einfluss auf den kindlichen Regulationsprozess}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-72322}, school = {Universit{\"a}t Potsdam}, year = {2013}, abstract = {Adipositas gilt seit einigen Jahren als eine der h{\"a}ufigsten chronischen Erkrankungen des Kindes- und Jugendalters. Welche Faktoren zu einer erfolgreichen Behandlung der Adipositas im Kindes- und Jugendalter f{\"u}hren, sind jedoch noch immer nicht ausreichend gekl{\"a}rt. Ein wichtiger - bisher jedoch weitgehend unbeachteter - Faktor, welcher m{\"o}glicherweise wegweisend f{\"u}r den Therapieverlauf sein kann, ist das subjektive Krankheitskonzept der betroffenen Kinder. Das bedeutsamste theoretische Modell, welches den Einfluss der individuellen Krankheitsvorstellungen auf den Regulationsprozess eines Menschen im Umgang mit Erkrankungen beschreibt, ist das Common Sense Model of Illness Representation (CSM) von Howard Leventhal. Ziel der vorliegenden Arbeit war es die subjektiven Krankheitskonzepte adip{\"o}ser Kinder zu erfassen und ihren Einfluss auf den Regulationsprozess zu analysieren. In einer ersten Untersuchung wurde mittels Daten von 168 adip{\"o}sen Kindern im Alter von 8 bis 12 Jahren zun{\"a}chst ein Fragebogen zur Erfassung der subjektiven Krankheitskonzepte entwickelt. Die Ergebnisse weisen darauf hin, dass der Fragebogen als reliabel und valide eingesch{\"a}tzt werden kann. Mit Hilfe dieses Fragebogens konnte nachgewiesen werden, dass adip{\"o}se Kinder Konstrukte {\"u}ber ihre Erkrankung haben, welche in eigenst{\"a}ndigen Dimensionen gespeichert werden. Die gefundenen initialen Krankheitskonzepte adip{\"o}ser Kinder ergeben ein homogenes erwartungskonformes Bild. In einer zweiten Untersuchung wurden anschließend die subjektiven Krankheitskonzepte adip{\"o}ser Kinder, die Bew{\"a}ltigungsstrategien sowie gesundheits- und krankheitsrelevante Kriteriumsvariablen untersucht. Die Befragungen erfolgten vor Beginn einer station{\"a}ren Reha (T1), am Ende der Reha (T2) sowie sechs Monate nach Reha-Ende (T3). Von 107 Kindern liegen Daten zu allen drei Messzeitpunkten vor. Es konnte ein Zusammenhang zwischen Krankheitskonzepten, Bew{\"a}ltigungsstrategien und spezifischen Kriteriumsvariablen bei adip{\"o}sen Kindern nachgewiesen werden. Die Analyse der Wirkzusammenh{\"a}nge konnte zeigen, dass die kindlichen Krankheitskonzepte - neben den indirekten Einfl{\"u}ssen {\"u}ber die Bew{\"a}ltigungsstrategien - die Kriteriumsvariablen vor allem auch direkt beeinflussen k{\"o}nnen. Der Einfluss der initialen Krankheitskonzepte adip{\"o}ser Kinder konnte hierbei sowohl im querschnittlichen als auch im l{\"a}ngsschnittlichen Design best{\"a}tigt werden. Zudem konnten vielf{\"a}ltige Einfl{\"u}sse der Ver{\"a}nderung der subjektiven Krankheitskonzepte w{\"a}hrend der Therapie gefunden werden. Die Ver{\"a}nderungen der Krankheitskonzepte wirken sowohl mittelfristig auf die individuellen Bew{\"a}ltigungsstrategien am Ende der Reha als auch l{\"a}ngerfristig auf die adipositasspezifischen Kriteriumsvariablen Gewicht, Ern{\"a}hrung, Bewegung und Lebensqualit{\"a}t. Die Befunde st{\"a}rken die Relevanz und das Potential der zielgerichteten Modifikation adaptiver bzw. maladaptiver Krankheitskonzepte innerhalb der station{\"a}ren Therapie der kindlichen Adipositas. Zudem konnte best{\"a}tigt werden, dass subjektive Krankheitskonzepte und ihre Ver{\"a}nderung innerhalb der Therapie einen relevanten Beitrag zur Vorhersage des kindlichen Therapieerfolgs {\"u}ber einen l{\"a}ngerfristigen Zeitraum leisten k{\"o}nnen.}, language = {de} } @phdthesis{Hudjetz2013, author = {Hudjetz, Annekatrin}, title = {Modelllernen im Ern{\"a}hrungskontext : m{\"u}tterlicher und v{\"a}terlicher Einfluss auf die Ern{\"a}hrung adip{\"o}ser Kinder}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-72336}, school = {Universit{\"a}t Potsdam}, year = {2013}, abstract = {Adipositas ist eine chronische Erkrankung mit erheblichen Komorbidit{\"a}ten und Folgesch{\"a}den, die bereits im Kindes- und Jugendalter weit verbreitet ist. Unterschiedliche Faktoren sind an der {\"A}tiologie dieser St{\"o}rung beteiligt. Die Ern{\"a}hrung stellt dabei eine der Haupts{\"a}ulen dar, auf welche immer wieder Bezug genommen wird. Der Einfluss der Eltern auf die kindliche Ern{\"a}hrung spielt unbestritten eine zentrale Rolle - hinsichtlich genetischer Dispositionen, aber auch als Gestalter der Lebensumwelten und Vorbilder im Ern{\"a}hrungsbereich. Die vorliegende Arbeit hat zum Ziel, {\"U}bereinstimmungen elterlicher und kindlicher Ern{\"a}hrung zu untersuchen und dabei zu pr{\"u}fen, inwiefern Prozesse des Modelllernens f{\"u}r die Zusammenh{\"a}nge verantwortlich zeichnen. Grundlage ist die sozial-kognitive Theorie Albert Banduras mit dem Fokus auf seinen Ausf{\"u}hrungen zum Beobachtungs- oder Modelllernen. Die Zusammenh{\"a}nge elterlicher und kindlicher Ern{\"a}hrung wurden anhand einer Stichprobe 7 - 13-j{\"a}hriger adip{\"o}ser Kinder und ihrer Eltern in Beziehung gesetzt zu den Bedingungen des Modelllernens, die zuvor auch in anderen Studien gefunden worden waren. Eine hohe {\"A}hnlichkeit oder gute Beziehung zwischen Modell (Mutter bzw. Vater) und Lernendem (Kind) sollte demnach moderierend auf die St{\"a}rke des Zusammenhangs wirken. Aus Banduras Ausf{\"u}hrungen zu den Phasen des Modelllernens ergibt sich zudem ein dritter Aspekt, der in das Untersuchungsmodell einbezogen wurde. Die von Bandura postulierte Aneignungsphase setzt voraus, dass das zu lernende Verhalten auch beobachtet werden kann. Aus diesem Grund sollte die Analyse von Zusammenh{\"a}ngen im Verhalten nicht losgel{\"o}st von der Zeit betrachtet werden, die Modell und Beobachter miteinander verbringen bzw. verbracht haben. Zudem wurde die Wahrnehmung eines Elternteils als Vorbild beim Kind erfragt und als Moderator aufgenommen. In die Analysen eingeschlossen wurden vollst{\"a}ndige Mutter-Vater-Kind-Triaden. Im Querschnitt der Fragebogenerhebung waren die Daten von 171 M{\"a}dchen und 176 Jungen, in einem 7 Monate darauf folgenden L{\"a}ngsschnitt insgesamt 75 Triaden (davon 38 M{\"a}dchen) enthalten. Es zeigte sich ein positiver Zusammenhang zwischen der kindlichen und m{\"u}tterlichen Ern{\"a}hrung ebenso wie zwischen der kindlichen und v{\"a}terlichen Ern{\"a}hrung. Die {\"U}bereinstimmungen zwischen Mutter und Kind waren gr{\"o}ßer als zwischen Vater und Kind. {\"U}berwiegend best{\"a}tigt werden konnten der moderierende Einfluss der Beziehungsqualit{\"a}t und der Vorbildwahrnehmung auf die Zusammenh{\"a}nge elterlicher und kindlicher gesunder Ern{\"a}hrung und der Einfluss gemeinsam verbrachter Zeit vor allem in Bezug auf Vater-Kind-Zusammenh{\"a}nge problematischer Ern{\"a}hrung. Der v{\"a}terliche Einfluss, der sowohl in Studien als auch in pr{\"a}ventiven oder therapeutischen Angeboten oft noch vernachl{\"a}ssigt wird und in vorliegender Arbeit besondere bzw. gleichberechtigte Beachtung fand, zeigte sich durch den Einbezug moderierender Variablen verst{\"a}rkt. Eine Ansprache von M{\"u}ttern und V{\"a}tern gleichermaßen ist somit unbedingtes Ziel bei der Pr{\"a}vention und Therapie kindlicher Adipositas. Auch jenseits des Adipositaskontextes sollten Eltern f{\"u}r die Bedeutung elterlicher Vorbildwirkung sensibilisiert werden, um eine gesunde Ern{\"a}hrungsweise ihrer Kinder zu f{\"o}rdern.}, language = {de} } @phdthesis{Wegewitz2007, author = {Wegewitz, Uta Elke}, title = {Genetische und metabolische Regulation von Adiponectin : Resultate von in vitro und humanen in vivo Studien}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-16062}, school = {Universit{\"a}t Potsdam}, year = {2007}, abstract = {{\"U}bergewicht, Diabetes oder Fettstoffwechselst{\"o}rungen sind mit erniedrigten Adiponectinspiegeln assoziiert. Eine Modulation des Adiponectins kann durch genetische und metabolische Gegebenheiten erfolgen. Das Ziel dieser Arbeit war die Analyse von Faktoren, welche die Adiponectinspiegel beeinflussen k{\"o}nnen, sowie eine Charakterisierung der Oligomerverteilung unter verschiedenen metabolischen Bedingungen. In der MeSyBePo-Kohorte waren die zirkulierenden Adiponectinspiegel mit den Promotorpolymorphismen ADIPOQ -11377 C/G und ADIPOQ -11391 G/A im Adiponectingen assoziiert. Im Hinblick auf die metabolischen Faktoren korrelierte Adiponectin eng mit Parametern des Glukose- und Fettstoffwechsels sowie dem {\"U}bergewicht. Innerhalb von hyperinsulin{\"a}mischen euglyk{\"a}mischen Clamps f{\"u}hrte eine akute Hyperinsulin{\"a}mie zu einer Abnahme der Adiponectinspiegel. Adiponectin zirkuliert im Serum als hochmolekulare (HMW), mittelmolekulare (MMW) und niedrigmolekulare (LMW) Spezies. Mit zunehmendem K{\"o}rpergewicht konnte eine Verlagerung von HMW-Spezies hin zu den LMW-Spezies beobachtet werden. Durch eine moderate Gewichtsabnahme erh{\"o}hten sich die Anteile an HMW- und MMW-Adiponectin wieder. W{\"a}hrend sich in Abh{\"a}ngigkeit vom Glukosemetabolismus keine Unterschiede in den Gesamtspiegeln ergaben, wurden bei Personen mit normaler Glukosetoleranz signifikant h{\"o}here Anteile an MMW-Adiponectin detektiert als bei Personen mit einem gest{\"o}rten Glukosestoffwechsel. Insgesamt scheinen die HMW- und MMW-Spezies gegens{\"a}tzlich zur LMW-Spezies reguliert zu werden. Die Arbeit unterstreicht die wichtige Rolle des Adiponectins im Glukose- und Fettstoffwechsel sowie bei einer Adipositas in vivo. Dabei waren {\"A}nderungen der Adiponectinspiegel bei Vorliegen von Insulinresistenz und Adipositas stets mit einer Umverteilung der Oligomerfraktionen verbunden. Vor allem die HMW- und MMW-Spezies des Adiponectins scheinen von entscheidender Bedeutung zu sein.}, language = {de} }