Bedeutung der ektopen Fettablagerung in Leber und Skelettmuskulatur für die Pathogenese des Metabolischen Syndroms

Zusammenfassung

Die Insulinresistenz, das heißt das verminderte Ansprechen der an sich insulinempfindlichen Gewebe Leber und Skelettmuskel auf die Stoffwechselwirkungen von Insulin, ist ein wesentlicher pathogenetischer Faktor in der Entstehung der Erkrankungen des Metabolischen Syndroms. Vermehrt anfallende Fettmetaboliten in diesen Geweben stören die Übertragung des Insulinsignals vom Insulinrezeptor an der Zelloberfläche. Hierdurch wird die insulinabhängige Glucoseaufnahme in Muskelzellen vermindert und in der Leber kann die Glucosefreisetzung nicht mehr durch Insulin unterdrückt werden. Beides begünstigt einen Blutzuckeranstieg und somit das Auftreten eines Diabetes mellitus. Ursachen dieser ektopen Fettablagerung sind eine vermehrte Freisetzung von Fettsäuren aus dem Fettgewebe, eine verminderte Oxidation von Fett in der Muskulatur und auch eine gesteigerte Fettsynthese in der Leber. Medikamente, die die ektope Fettablagerung in Leber und Muskulatur vermindern, stellen einen neuen Therapieansatz in der Behandlung der mit dem Metabolischen Syndrom assoziierten Erkrankungen dar.

Summary

An impaired response of usually insulin sensitive tissues such as skeletal muscle and liver to the metabolic actions of insulin, also referred to as insulin resistance, is a hallmark feature of the metabolic syndrome. Importantly, skeletal muscle and liver insulin resistance are associated with ectopic fat deposition in these tissues. Increased intracellular fat metabolites have been shown to impair insulin signalling, thereby resulting in impaired insulin mediated glucose transport in skeletal muscle and diminished suppression of hepatic glucose production. Enhanced release of fatty acids from subcutaneous and visceral adipose tissue stores, impaired skeletal muscle fatty acid oxidation and increased hepatic fat synthesis are important contributors to the observed increase in ectopic fat deposition. Strategies targeted at repartitioning fat from muscle and liver represent a novel therapeutic approach to the metabolic syndrome and its associated diseases.

Insulinresistenz - Fettsäuren - Nicht-alkoholische Fettlebererkrankung

Insulin resistance - intramyocellular fat - non-alcoholic fatty liver disease - fatty acids

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