Lipid Metabolism in the Liver

Zusammenfassung

Als zentrales Stoffwechselorgan nimmt die Leber eine Schlüsselrolle bei der Metabolisierung hochkalorischer, insbesondere fettreicher Ernährung ein. Im Zusammenspiel mit dem Gastrointestinaltrakt, dem Fett- und Muskelgewebe und anderen Organsystemen ist die Leber entscheidend am Fettmetabolismus beteiligt. Durch Aktivierung von Transkriptionsfaktoren wie dem „carbohydrate responsive element binding protein (ChREBP)”, „sterol response element binding protein-1c (SREBP-1c)” oder der „forkhead box 01 (Fox01)” wird die Fettsäuresynthese gesteigert. Die Translokation von freien Fettsäuren wird über bestimmte Fetttransportproteine wie dem „fatty acid transport proteins (FATP)”, der „fatty acid translocase (FAT/CD36)”, Caveolin-1 und dem „fatty acid binding protein (FABP)” vermittelt. Bei Störungen des Fettmetabolismus oder bei übermäßigem Fettangebot kommt es häufig zu Fettablagerungen in Form von Lipidtröpfchen innerhalb der Hepatozyten (nichtalkoholische Fettlebererkrankung; alkoholische Steatohepatitis, akute Schwangerschaftsfettleber, Hepatitis C). Neuere Daten belegen interessanterweise, dass die Fettablagerung in den Hepatozyten für die Leberregenration essenziell ist. Hieraus ergibt sich zunehmend die Erkenntnis, dass die Steatosis nicht ausschließlich das Resultat einer Stoffwechselstörung ist. Vielmehr scheinen bereits kleinste Veränderungen in der β-Oxidation, bei Transportproteinen und/oder den Signalwegen eine Steatosis zu bedingen und das Fortschreiten der o. a. Lebererkrankungen voranzutreiben. Durch neue experimentelle Erkenntnisse über die Mechanismen der Leberverfettung ergeben sich potenzielle neue therapeutische Optionen.

Abstract

As a key metabolic organ, the liver is central to the imbalance of high-caloric diets, and particularly dietary fat consumption, in the industrialized countries and their association with the increasing prevalence of morbid obesity. By interacting with the intestinal tract and adipose tissue, the liver plays a key role in various aspects of lipid metabolism. Increasing activation of transcription factors, such as carbohydrate responsive element binding protein (ChREBP), sterol response element binding protein-1c (SREBP-1c), or forkhead box 01 (Fox01), may contribute to fatty acid synthesis. Their translocation occurs via fatty acid transporters such as fatty acid transport proteins (FATP), fatty acid translocase (FAT/CD36), caveolin-1 and fatty acid binding protein (FABP). Eventually, the accumulation of fat in the form of lipid droplets within the hepatocytes results in hepatic steatosis which, indeed, is a hallmark of liver diseases such as non-alcoholic fatty liver disease, alcoholic fatty liver, acute fatty liver in pregnancy, and hepatitis C. In contrast, lipid accumulation within hepatocytes during liver regeneration is essential. It is thus now becoming clear that steatosis is not only a mere consequence of metabolic imbalance, but that it is also a result of discrete alterations in the β-oxidation, transport mechanisms, and signaling pathways involved in the synthesis, systemic traffic modalities, and cellular effects of fatty acids. Such a novel insight offers potential options for improved treatment.

Schlüsselwörter

fettreiche Ernährung - Fetttransportproteine - freie Fettsäure - NAFLD

Key words

dietary lipids - fatty acid transport proteins - free fatty acids - NAFLD

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