The literature describes a close correlation between metabolic disorders and abnormal immune responses, like low-grade inflammation (LGI), which may be one mechanistic link between obesity and various comorbidities, including non-alcoholic fatty liver disease (NAFLD). In our study, we investigated the influence of dietary composition on obesity-derived LGI in the liver. We used a dietary induced obesity mouse model of C57BL/6J mice fed with high fat diet (HFD, 60% fat, 20% protein, 20% carbohydrates) and two different controls. One was rich in carbohydrates (10% fat, 20% protein, 70% carbohydrates), further referred to as the control diet (CD), and the other one is referred to as the standard diet (SD), with a more balanced macronutrient content (9% fat, 33% protein, 58% carbohydrates). Our results showed a significant increased NAFLD activity score in HFD compared to both controls, but livers of the CD group also differed in their macroscopic appearance from healthy livers. Hepatic fat content showed significantly elevated cholesterol concentrations in the CD group. Histologic analysis of the cellular immune response in the liver showed no difference between HFD and CD and expression analysis of immunologic mediators like interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor alpha also point towards a pro-inflammatory response to CD, comparable to LGI in HFD. Therefore, when studying diet-induced obesity with a focus on inflammatory processes, we encourage researchers to carefully select controls and not use a control diet disproportionally rich in carbohydrates.
Obesity is one of the most challenging diseases of the 21st century and is accompanied by behavioural disorders. Exercise, dietary adjustments, or time-restricted feeding are the only successful long-term treatments to date. Fibroblast growth factor 21 (FGF21) plays a key role in dietary regulation, but FGF21 resistance is prevalent in obesity. The aim of this study was to investigate in obese mice whether weight reduction leads to improved behaviour and whether these behavioural changes are associated with decreased plasma FGF21 levels. After establishing a model for diet-induced obesity, mice were subjected to three different interventions for weight reduction, namely dietary change, treadmill exercise, or time-restricted feeding. In this study, we demonstrated that only the combination of dietary change and treadmill exercise affected all parameters leading to a reduction in weight, fat, and FGF21, as well as less anxious behaviour, higher overall activity, and improved olfactory detection abilities. To investigate the interrelationship between FGF21 and behavioural parameters, feature selection algorithms were applied designating FGF21 and body weight as one of five highly weighted features. In conclusion, we concluded from the complementary methods that FGF21 can be considered as a potential biomarker for improved behaviour in obese mice after weight reduction.
Einleitung: Voraussetzung für die Approbation im Rahmen der neuen Psychotherapeutenausbildung ist u.a. das Bestehen einer anwendungsorientierten Parcoursprüfung. Da diese Prüfung von Lehrenden und Studierenden als Herausforderung angesehen wird, wurde eine Kurzform der Parcoursprüfung im Rahmen einer Modulprüfung des MSc-Studiengangs Psychologie eingeführt und evaluiert. Methode: Für die 15-minütige Parcoursprüfung wurden 9 Kompetenzbereiche basierend auf praxisorientierten Psychotherapieseminaren entwickelt, von denen 2 jeweils geprüft wurden. Zur Standardisierung der Benotung wurde ein Bewertungsbogen konzipiert. Eine Mitarbeiterin erhielt ein Training als Simulationspatientin. Für die Evaluation wurde ein Fragebogen entwickelt, welcher u.a. die Umsetzbarkeit und das subjektive Erleben dieses Prüfungsformats aus der Sicht der an der Prüfung beteiligten Personen erfasst. Ergebnisse: 14 Prüfungskandidierende ließen sich durch 3 Prüfende prüfen. Die Gesamtdurchschnittsnote betrug 1,19 (Bereich: 1,0–2,3). Die Auswertung der Fragebögen zeigte, dass alle drei Gruppen die Prüfung als geeignet, die praktischen Fertigkeiten abzubilden, objektiv und praxisnah empfanden. Von den Prüfungskandidierenden gaben 50% an, dass die Prüfung sie gestresst habe, während die Simulationspatientin sich nie und die Prüfenden sich gar nicht (78%) oder kaum (22%) gestresst fühlten. Diskussion: Die Ergebnisse dieser Pilotstudie weisen auf eine gute Umsetzbarkeit der Parcoursprüfung hin, wenngleich sie auch mit Stress für die Prüfungskandidierenden verbunden war. Die Pilotstudie wird limitiert durch eine kleine und wahrscheinlich verzerrte Stichprobe (motivierte Studierende) ohne Vergleichsgruppe. Abschließend werden die Vor- und Nachteile dieses Prüfungsmodells kritisch diskutiert.
ObjectiveObesity, often associated with non-alcoholic fatty liver disease (NAFLD), is characterized by an imbalance between energy expenditure and food intake, which is also reflected by desensitization of fibroblast growth factor 21 (FGF21). FGF21 is strongly influenced, among others, by TNFα, which is known to be upregulated in obesity-induced inflammation. Successful long-term treatments of NAFLD might be dietary modification, exercise, or fasting.Materials and methodsWhether succeeded NAFLD recovery is linked with improved FGF21 sensitivity and finally reverted FGF21 resistance was the focus of the present study. For this purpose, mice received a high-fat diet (HFD) for 6 months to establish obesity. Afterward, the mice were subjected to three different weight loss interventions, namely, dietary change to low-fat diet (LFD), treadmill training, and/or time-restricted feeding for additional 6 months, whereas one group remained on HFD.ResultsIn addition to the expected decrease in NAFLD activity with dietary change, this was also observed in the HFD group with additional time-restricted feeding. There was also an associated decrease in hepatic TNFα and FGF21 expression and an increase in ß-klotho expression, demonstrated mainly by using principal component analysis. Pearson correlation analysis shows that independent of any intervention, TNFα expression decreased with improved NAFLD recovery. This was accompanied with higher FGF21 sensitivity, as expressed by an increase in β-klotho and FGFR1c expression and concomitantly decreased FGF21 levels.ConclusionIn summary, we conclude that successful NAFLD therapy is associated with a reversion of the TNFα-triggered FGF21-resistant state or desensitization.
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