Epigenetik der Adipositas: Ergebnisse aus Mausstudien

Zusammenfassung

Vor dem Hintergrund der steigenden Prävalenz von Adipositas und den damit einhergehenden Begleiterkrankungen (Nicht-alkoholische Fettleber, Typ-2-Diabetes u.a.) wird es immer wichtiger, neue Präventions- und Behandlungsmöglichkeiten aufzuzeigen, die eine personalisierte Therapie ermöglichen. Die Entdeckung von Veränderungen in bestimmten Signalwegen, die durch Adipositas ausgelöst werden, verbessern nicht nur unsere Kenntnisse über die Pathophysiologie, sie können zudem auf neue pharmakologische Behandlungsstrategien hinweisen. Seit mehreren Jahren befasst sich die Forschung auch damit, die Beteiligung epigenetischer Mechanismen bei der Entstehung der Adipositas zu klären. Experimentelle Studien an Mäusen führten zu der Erkenntnis, dass der Ernährungszustand der Eltern epigenetisch vererbt wird und so die Prävalenz der Nachkommen an Übergewicht und Insulinresistenz zu erkranken beeinflusst. Des Weiteren wurden interindividuelle Varianzen der DNA-Methylierung identifiziert, die das Risiko an Übergewicht und einer Fettleber zu leiden erhöhten. Diese Erkenntnisse können einerseits genutzt werden, um epigenetische Biomarker zu identifizieren, welche das individuelle Risiko besser bewerten können, anderseits um pharmakologische Therapien personalisierter einzusetzen.

Summary

In view of the fact that prevalence of obesity and its co-morbidities (e.g. NAFLD and type 2 diabetes) are increasing, it becomes more and more important to evaluate new prevention and treatment strategies and to facilitate personalized therapy. The identification of alterations within particular pathways affected in obesity improves our knowledge of pathophysiology and can point to novel pharmacological treatment strategies. In recent years, research on epigenetic mechanisms involved in weight regulation came in focus. Experimental studies have been able to show that the nutritional status of parental mice is epigenetically inherited to the next generation and alters prevalence for obesity and insulin resistance. Furthermore, interindividual variations in DNA methylation, which increase the prevalence for obesity and fatty liver, were identified. In the future, the detection of epigenetic biomarkers could improve individual risk assessment for obesity and comorbidities as well as personalized pharmacological therapy.

Schlüsselwörter

Adipositas - DNA-Methylierung - transgenerationale Epigenetik

Keywords

Obesity - missing heritability - DNA methylation - transgenerational epigenetics

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