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Leptin — Neue Erkenntnisse zur Pathogenese der Adipositas

Leptin — Novel concepts of the pathophysiology of obesity

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Zusammenfassung

□ Die Entdeckung des ob-Gens und seines Genproduktes Leptin führte zur Identifizierung eines schon seit Jahrzehnten postulierten «Sättigungsfaktors», der im Rahmen der Körpergewichtsregulation das Gehim über die peripheren Fettspeicher informiert und die weitere Nahrungsaufnahme reguliert. Schon bald wurde ein leptinbindender Rezeptor sowohl im Zentralnervensystem als auch in zahlreichen peripheren Organen identifiziert. Ein geschlossener Regelkreis zwischen peripheren Fettspeichern und zentralnervösem Leptinrezeptor scheint die Grundlage einer intakten Körpergewichtsregulation zu sein. Während die Adipositas des Menschen mit einer Resistenz gegenüber körpereigenem Leptin assoziiert ist, deren Ursachen noch weitgehend unbekannt sind, beruht die Adipositas verschiedener Tiermodelle auf der Unterbrechung dieses Regelkreises an unterschiedlichen Stellen. Auch bei der Manifestation von Insulinresistenz und Diabetes mellitus Typ II scheint Leptin eine mögliche Rolle zu spielen.

□ Nach Jahren der Stagnation in der Grundlagenforschung zur Adipositas konnten seit der Entdeckung von Leptin zahlreiche neue Erkenntnisse über die an der Adipositas beteiligten molekularen Mechanismen und Signaltransduktionswege gewonnen werden. Hieraus dürften sich neue, kausal orientierte Strategien zur Therapie der Adipositas ergeben.

Abstract

□ Cloning of the ob-gene and characterization of its gene product leptin has led to the identification of a satiety factor, which signals the amount of peripheral fat stores to the central nervous system and regulates further feeding behaviour, thus playing a central role in the regulation of body weight. Soon after cloning of the ob-gene, a leptin-binding receptor has been identified in the central nervous system as well as in various peripheral organs. A feedback loop between peripheral fat stores and leptin receptors in the central nervous system appears to play an important role in normal body weight regulation. In contrast to human obesity, which associated with leptin resistance of uncertain etiology, the obesity syndromes associated with several animal models are now known to result from the interruption of the feedback loop at different points. Moreover, leptin may play a role in manifestation of insulin resistance and type II diabetes.

□ Since the identification of leptin, a vast number of studies have been conducted to assess the molecular mechanisms and signal transduction pathways that are involved in the development and manifestation of obesity. From the large body of data generated to date, novel concepts of the regulation of energy balance and target strategies to control human obesity should soon be forthcoming.

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  1. Medizinische Klinik, Klinikum Innenstadt der Ludwig-Maximilians-Universität München, Ziemssenstraße 1, D-80336, München

    Christine Spitzweg, Werner Joba & Armin E. Heufelder

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  1. Christine Spitzweg
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Spitzweg, C., Joba, W. & Heufelder, A.E. Leptin — Neue Erkenntnisse zur Pathogenese der Adipositas. Med Klin 93, 478–485 (1998). https://doi.org/10.1007/BF03042597

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