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Semin Liver Dis 2001; 21(1): 089-104
DOI: 10.1055/s-2001-12932
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Animal Models of Steatosis

Ayman Koteish, Anna Mae Diehl
  • The Johns Hopkins University, Baltimore, Maryland
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Publikationsverlauf

Publikationsdatum:
31. Dezember 2001 (online)

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ABSTRACT

The lipid content of hepatocytes is regulated by the integrated activities of cellular enzymes that catalyze lipid uptake, synthesis, oxidation, and export. When ``input'' of fats into these systems (either because of increased fatty acid delivery, hepatic fatty acid uptake, or fatty acid synthesis) exceeds the capacity for fatty acid oxidation or export (i.e., ``output''), then hepatic steatosis occurs. Genetic causes of increased fatty acid input promote excessive hepatic lipogenesis. These include mutations that cause leptin deficiency or leptin receptor inhibition and mutations that induce insulin, insulin-like growth factors, or insulin-responsive transcription factors. Genetic causes of impaired hepatic fatty acid oxidation inhibit the elimination (i.e., output) of fat from the liver. These include mutations that inhibit various components of the peroxisomal and/or mitochondrial pathways for fatty acid β-oxidation. Environmental factors, such as diets and toxins, can also unbalance hepatic fatty acid synthesis and oxidation. Hepatic lipogenesis is increased by dietary sucrose, fructose, or fats and certain toxins, such as ethanol. Hepatic fatty acid oxidation is inhibited by choline- or methionine-deficient diets and other toxins, such as etomoxir. Animals with genetic or environmental induction of hepatic lipogenesis appear to be useful models for human nonalcoholic fatty liver disease in which hyperinsulinemia and defective leptin signaling are conspicuous at early stages of the disease process.

KEYWORD

Leptin - insulin - mitochondria - peroxisomes - energy

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