Die Brücke zwischen Labor und Klinik: Wie humangenetische Untersuchungen die Therapie bei genetischer Adipositas leiten

Zusammenfassung

Krankheitsauslösende Genveränderungen, die zu einer pathologischen Hunger-Sättigungs-Dysregulation (Hyperphagie) im Hypothalamus führen, können frühmanifeste, extreme Formen von Adipositas verursachen. Da diese Formen im klinischen Alltag häufig schwer von multifaktorieller Adipositas zu unterscheiden sind, hat die humangenetische Diagnostik einen bedeutenden Stellenwert in der Behandlung von Personen mit extremer Adipositas. Als Brücke zwischen Labor und Klinik ermöglicht sie nicht nur einen Einblick in die Pathogenese extremer Adipositas, sondern beeinflusst auch die Auswahl personalisierter Therapieempfehlungen für die Betroffenen. Dabei ist die Hyperphagie ein zentraler Ansatzpunkt: Einerseits sollte sie durch Lebensstilmodifikationen, insbesondere durch die Vermittlung verhaltenstherapeutischer Strategien zum Umgang mit der unphysiologischen Hunger-Sättigungsregulation, adressiert werden. Andererseits erlaubt die Kenntnis der genetischen Ursache bei bestimmten Formen von Adipositas den Einsatz Mechanismus-basierter pharmakologischer Therapien. Darüber hinaus trägt humangenetische Forschung durch die Identifikation von neuen Adipositas-assoziierten Genen und Signalwegen zur Entwicklung neuer Therapiestrategien mit innovativen Ansätzen bei.

Abstract

Disease-causing genetic alterations that lead to an abnormal regulation of hunger and satiety (hyperphagia) in the hypothalamus can cause early-onset, severe forms of obesity. Since these forms are often difficult to distinguish from common obesity in clinical practice, genetic testing plays a crucial role in the clinical care of patients with extreme obesity. Serving as a bridge between the laboratory and the clinic, it not only provides insight into the pathogenesis of extreme obesity but also influences the conception of personalized therapeutic recommendations for affected individuals. In this context, hyperphagia represents a central target: on one hand, it should be addressed through lifestyle modifications and, in particular, through the implementation of behavioural therapeutic strategies to manage the abnormal hunger-satiety regulation. On the other hand, knowledge of the genetic cause in certain forms of obesity allows for the application of targeted mechanism-based pharmacological therapies. Beyond this, genetic research contributes to the development of novel therapeutic strategies with innovative approaches through the identification of new obesity-associated genes and signalling pathways.

Schlüsselwörter

Hyperphagie - extreme Adipositas - individualisierte Therapie - Leptin-Melanokortin-Signalweg

Keywords

hyperphagia - severe obesity - person-tailored treatment - leptin-melanocortin-pathway

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