@article{BusseSimonPetroffetal.2022, author = {Busse, David and Simon, Philipp and Petroff, David and El-Najjar, Nahed and Schmitt, Lisa and Bindellini, Davide and Dietrich, Arne and Zeitlinger, Markus and Huisinga, Wilhelm and Michelet, Robin and Wrigge, Hermann and Kloft, Charlotte}, title = {High-dosage fosfomycin results in adequate plasma and target-site exposure in morbidly obese and nonobese nonhyperfiltration patients}, series = {Antimicrobial agents and chemotherapy}, volume = {66}, journal = {Antimicrobial agents and chemotherapy}, number = {6}, publisher = {American Society for Microbiology}, address = {Washington}, issn = {0066-4804}, doi = {10.1128/aac.02302-21}, pages = {12}, year = {2022}, abstract = {The objectives of this study were the identification in (morbidly) obese and nonobese patients of (i) the most appropriate body size descriptor for fosfomycin dose adjustments and (ii) adequacy of the currently employed dosing regimens. Plasma and target site (interstitial fluid of subcutaneous adipose tissue) concentrations after fosfomycin administration (8 g) to 30 surgery patients (15 obese/15 nonobese) were obtained from a prospective clinical trial. After characterization of plasma and microdialysis-derived target site pharmacokinetics via population analysis, short-term infusions of fosfomycin 3 to 4 times daily were simulated. The adequacy of therapy was assessed by probability of pharmacokinetic/pharmacodynamic target attainment (PTA) analysis based on the unbound drug-related targets of an \%fT(>= MIC) (the fraction of time that unbound fosfomycin concentrations exceed the MIC during 24 h) of 70 and an fAUC(0-24h)/MIC (the area under the concentration-time curve from 0 to 24 h for the unbound fraction of fosfomycin relative to the MIC) of 40.8 to 83.3. Lean body weight, fat mass, and creatinine clearance calculated via adjusted body weight (ABW) (CLCRCG_ABW) of all patients (body mass index [BMI] = 20.1 to 52.0 kg/m(2)) explained a considerable proportion of between-patient pharmacokinetic variability (up to 31.0\% relative reduction). The steady-state unbound target site/plasma concentration ratio was 26.3\% lower in (morbidly) obese than nonobese patients. For infections with fosfomycin-susceptible pathogens (MIC <= 16 mg/L), intermittent "high-dosage" intravenous (i.v.) fosfomycin (8 g, three times daily) was sufficient to treat patients with a CLCRCG_ABW of,130 mL/min, irrespective of the pharmacokinetic/pharmacodynamic indices considered. For infections by Pseudomonas aeruginosa with a MIC of 32 mg/L, when the index fAUC0-24h/MIC is applied, fosfomycin might represent a promising treatment option in obese and nonobese patients, especially in combination therapy to complement beta-lactams, in which carbapenem-resistant P. aeruginosa is critical. In conclusion, fosfomycin showed excellent target site penetration in obese and nonobese patients. Dosing should be guided by renal function rather than obesity status.}, language = {en} } @article{LehnStefanPeterMachannetal.2022, author = {Lehn-Stefan, Angela and Peter, Andreas and Machann, J{\"u}rgen and Schick, Fritz and Randrianarisoa, Elko and Heni, Martin and Wagner, Robert and Birkenfeld, Andreas L. and Fritsche, Andreas and Schulze, Matthias Bernd and Stefan, Norbert and Kantartzis, Konstantinos}, title = {Impaired metabolic health and low cardiorespiratory fitness independently associate with subclinical atherosclerosis in obesity}, series = {The journal of clinical endocrinology \& metabolism}, volume = {107}, journal = {The journal of clinical endocrinology \& metabolism}, number = {6}, publisher = {Endocrine Society}, address = {Washington}, issn = {0021-972X}, doi = {10.1210/clinem/dgac091}, pages = {E2417 -- E2424}, year = {2022}, abstract = {Context For a given body mass index (BMI), both impaired metabolic health (MH) and reduced cardiorespiratory fitness (CRF) associate with increased risk of cardiovascular disease (CVD). Objective It remains unknown whether both risk phenotypes relate to CVD independently of each other, and whether these relationships differ in normal weight, overweight, and obese subjects. Methods Data from 421 participants from the Tubingen Diabetes Family Study, who had measurements of anthropometrics, metabolic parameters, CRF (maximal aerobic capacity [VO2max]) and carotid intima-media thickness (cIMT), an early marker of atherosclerosis, were analyzed. Subjects were divided by BMI and MH status into 6 phenotypes. Results In univariate analyses, older age, increased BMI, and a metabolic risk profile correlated positively, while insulin sensitivity and VO2max negatively with cIMT. In multivariable analyses in obese subjects, older age, male sex, lower VO2max (std. ss -0.21, P = 0.002) and impaired MH (std. ss 0.13, P = 0.02) were independent determinants of increased cIMT. After adjustment for age and sex, subjects with metabolically healthy obesity (MHO) had higher cIMT than subjects with metabolically healthy normal weight (MHNW; 0.59 +/- 0.009 vs 0.52 +/- 0.01 mm; P < 0.05). When VO2max was additionally included in this model, the difference in cIMT between MHO and MHNW groups became statistically nonsignificant (0.58 +/- 0.009 vs 0.56 +/- 0.02 mm; P > 0.05). Conclusion These data suggest that impaired MH and low CRF independently determine increased cIMT in obese subjects and that low CRF may explain part of the increased CVD risk observed in MHO compared with MHNW.}, language = {en} } @article{HenningKochlikKuschetal.2022, author = {Henning, Thorsten and Kochlik, Bastian Max and Kusch, Paula and Strauss, Matthias and Juric, Viktorija and Pignitter, Marc and Marusch, Frank and Grune, Tilman and Weber, Daniela}, title = {Pre-Operative assessment of micronutrients, amino acids, phospholipids and oxidative stress in bariatric surgery candidates}, series = {Antioxidants : open access journal}, volume = {11}, journal = {Antioxidants : open access journal}, number = {4}, publisher = {MDPI}, address = {Basel}, issn = {2076-3921}, doi = {10.3390/antiox11040774}, pages = {13}, year = {2022}, abstract = {Obesity has been linked to lower concentrations of fat-soluble micronutrients and higher concentrations of oxidative stress markers as well as an altered metabolism of branched chain amino acids and phospholipids. In the context of morbid obesity, the aim of this study was to investigate whether and to which extent plasma status of micronutrients, amino acids, phospholipids and oxidative stress differs between morbidly obese (n = 23) and non-obese patients (n = 13). In addition to plasma, malondialdehyde, retinol, cholesterol and triglycerides were assessed in visceral and subcutaneous adipose tissue in both groups. Plasma gamma-tocopherol was significantly lower (p < 0.011) in the obese group while other fat-soluble micronutrients showed no statistically significant differences between both groups. Branched-chain amino acids (all p < 0.008) and lysine (p < 0.006) were significantly higher in morbidly obese patients compared to the control group. Malondialdehyde concentrations in both visceral (p < 0.016) and subcutaneous (p < 0.002) adipose tissue were significantly higher in the morbidly obese group while plasma markers of oxidative stress showed no significant differences between both groups. Significantly lower plasma concentrations of phosphatidylcholine, phosphatidylethanolamine, lyso-phosphatidylethanolamine (all p < 0.05) and their corresponding ether-linked analogs were observed, which were all reduced in obese participants compared to the control group. Pre-operative assessment of micronutrients in patients undergoing bariatric surgery is recommended for early identification of patients who might be at higher risk to develop a severe micronutrient deficiency post-surgery. Assessment of plasma BCAAs and phospholipids in obese patients might help to differentiate between metabolic healthy patients and those with metabolic disorders.}, language = {en} } @article{GoeldelKamrathMindenetal.2022, author = {G{\"o}ldel, Julia Marlen and Kamrath, Clemens and Minden, Kirsten and Wiegand, Susanna and Lanzinger, Stefanie and Sengler, Claudia and Weihrauch-Bl{\"u}her, Susann and Holl, Reinhard 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} } @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} } @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 Silvia 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} }