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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.
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.
Adipositas gilt seit einigen Jahren als eine der häufigsten chronischen Erkrankungen des Kindes- und Jugendalters. Welche Faktoren zu einer erfolgreichen Behandlung der Adipositas im Kindes- und Jugendalter führen, sind jedoch noch immer nicht ausreichend geklärt. Ein wichtiger – bisher jedoch weitgehend unbeachteter – Faktor, welcher möglicherweise wegweisend für 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 adipöser Kinder zu erfassen und ihren Einfluss auf den Regulationsprozess zu analysieren. In einer ersten Untersuchung wurde mittels Daten von 168 adipösen Kindern im Alter von 8 bis 12 Jahren zunächst ein Fragebogen zur Erfassung der subjektiven Krankheitskonzepte entwickelt. Die Ergebnisse weisen darauf hin, dass der Fragebogen als reliabel und valide eingeschätzt werden kann. Mit Hilfe dieses Fragebogens konnte nachgewiesen werden, dass adipöse Kinder Konstrukte über ihre Erkrankung haben, welche in eigenständigen Dimensionen gespeichert werden. Die gefundenen initialen Krankheitskonzepte adipöser Kinder ergeben ein homogenes erwartungskonformes Bild. In einer zweiten Untersuchung wurden anschließend die subjektiven Krankheitskonzepte adipöser Kinder, die Bewältigungsstrategien sowie gesundheits- und krankheitsrelevante Kriteriumsvariablen untersucht. Die Befragungen erfolgten vor Beginn einer stationären 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, Bewältigungsstrategien und spezifischen Kriteriumsvariablen bei adipösen Kindern nachgewiesen werden. Die Analyse der Wirkzusammenhänge konnte zeigen, dass die kindlichen Krankheitskonzepte – neben den indirekten Einflüssen über die Bewältigungsstrategien – die Kriteriumsvariablen vor allem auch direkt beeinflussen können. Der Einfluss der initialen Krankheitskonzepte adipöser Kinder konnte hierbei sowohl im querschnittlichen als auch im längsschnittlichen Design bestätigt werden. Zudem konnten vielfältige Einflüsse der Veränderung der subjektiven Krankheitskonzepte während der Therapie gefunden werden. Die Veränderungen der Krankheitskonzepte wirken sowohl mittelfristig auf die individuellen Bewältigungsstrategien am Ende der Reha als auch längerfristig auf die adipositasspezifischen Kriteriumsvariablen Gewicht, Ernährung, Bewegung und Lebensqualität. Die Befunde stärken die Relevanz und das Potential der zielgerichteten Modifikation adaptiver bzw. maladaptiver Krankheitskonzepte innerhalb der stationären Therapie der kindlichen Adipositas. Zudem konnte bestätigt werden, dass subjektive Krankheitskonzepte und ihre Veränderung innerhalb der Therapie einen relevanten Beitrag zur Vorhersage des kindlichen Therapieerfolgs über einen längerfristigen Zeitraum leisten können.
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.
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.
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.
Prevention and anthropology
(2014)
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.
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
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.
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.
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.
Adipositas ist eine chronische Erkrankung mit erheblichen Komorbiditäten und Folgeschäden, die bereits im Kindes- und Jugendalter weit verbreitet ist. Unterschiedliche Faktoren sind an der Ätiologie dieser Störung beteiligt. Die Ernährung stellt dabei eine der Hauptsäulen dar, auf welche immer wieder Bezug genommen wird. Der Einfluss der Eltern auf die kindliche Ernährung spielt unbestritten eine zentrale Rolle – hinsichtlich genetischer Dispositionen, aber auch als Gestalter der Lebensumwelten und Vorbilder im Ernährungsbereich. Die vorliegende Arbeit hat zum Ziel, Übereinstimmungen elterlicher und kindlicher Ernährung zu untersuchen und dabei zu prüfen, inwiefern Prozesse des Modelllernens für die Zusammenhänge verantwortlich zeichnen. Grundlage ist die sozial-kognitive Theorie Albert Banduras mit dem Fokus auf seinen Ausführungen zum Beobachtungs- oder Modelllernen. Die Zusammenhänge elterlicher und kindlicher Ernährung wurden anhand einer Stichprobe 7 – 13-jähriger adipöser Kinder und ihrer Eltern in Beziehung gesetzt zu den Bedingungen des Modelllernens, die zuvor auch in anderen Studien gefunden worden waren. Eine hohe Ähnlichkeit oder gute Beziehung zwischen Modell (Mutter bzw. Vater) und Lernendem (Kind) sollte demnach moderierend auf die Stärke des Zusammenhangs wirken. Aus Banduras Ausführungen 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 Zusammenhängen im Verhalten nicht losgelöst 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 vollständige Mutter-Vater-Kind-Triaden. Im Querschnitt der Fragebogenerhebung waren die Daten von 171 Mädchen und 176 Jungen, in einem 7 Monate darauf folgenden Längsschnitt insgesamt 75 Triaden (davon 38 Mädchen) enthalten. Es zeigte sich ein positiver Zusammenhang zwischen der kindlichen und mütterlichen Ernährung ebenso wie zwischen der kindlichen und väterlichen Ernährung. Die Übereinstimmungen zwischen Mutter und Kind waren größer als zwischen Vater und Kind. Überwiegend bestätigt werden konnten der moderierende Einfluss der Beziehungsqualität und der Vorbildwahrnehmung auf die Zusammenhänge elterlicher und kindlicher gesunder Ernährung und der Einfluss gemeinsam verbrachter Zeit vor allem in Bezug auf Vater-Kind-Zusammenhänge problematischer Ernährung. Der väterliche Einfluss, der sowohl in Studien als auch in präventiven oder therapeutischen Angeboten oft noch vernachlässigt wird und in vorliegender Arbeit besondere bzw. gleichberechtigte Beachtung fand, zeigte sich durch den Einbezug moderierender Variablen verstärkt. Eine Ansprache von Müttern und Vätern gleichermaßen ist somit unbedingtes Ziel bei der Prävention und Therapie kindlicher Adipositas. Auch jenseits des Adipositaskontextes sollten Eltern für die Bedeutung elterlicher Vorbildwirkung sensibilisiert werden, um eine gesunde Ernährungsweise ihrer Kinder zu fördern.
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.
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.
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.
Hauptziel Adipositas ist eine der Hauptindikationen in der Kinder- und Jugend-Rehabilitation. Für ältere Jugendliche und junge Erwachsene fehlen altersspezifische Therapieangebote fast vollständig. Ziel war es die Wünsche bezüglich der Inhalte und Methoden einer „perfekten Therapie“ im Rahmen eines Rehabilitationsaufenthalts zu untersuchen.
Methode Im Rahmen der YOUTH-Studie wurden 147 adipöse 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. Interdisziplinär geleitete, koedukative Gruppen mit Elterneinbindung wurden gewünscht. Wichtige Themen waren gesunde Ernährung sowie psychosoziale Aspekte. Auch der Prävention von Rückfällen wurde eine hohe Relevanz zugeschrieben.
Schlussfolgerung Psychosoziale Aspekte und die Vorbereitung auf mögliche Rückfallsituationen sollten integraler Bestandteil der Therapie sein.
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.
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.
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.
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.