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Semin Liver Dis 2010; 30(4): 378-390
DOI: 10.1055/s-0030-1267538
© Thieme Medical PublishersDOI: 10.1055/s-0030-1267538
The Role of Lipid Metabolism in the Pathogenesis of Alcoholic and Nonalcoholic Hepatic Steatosis
Further Information
Publication History
Publication Date:
19 October 2010 (online)
ABSTRACT
Hepatic steatosis is now understood to play an important role in the development of advanced liver disease. Alcoholic and nonalcoholic fatty liver each begin with the accumulation of lipids in the liver. Lipid accumulation in the liver can occur through maladaptations of fatty acid uptake (either through dietary sources or from fat tissue), fatty acid synthesis, fatty acid oxidation, or export of lipids from the liver. Alterations in mechanisms of fatty acid uptake through both dietary uptake and lipolysis in adipose tissue can contribute to the pathogenesis of both disorders, as can effects on fatty acid transporters. Effects on lipid synthesis in alcoholic and nonalcoholic fatty liver involve the endoplasmic reticulum (ER) stress response, homocysteine metabolism pathway, and different transcription factors regulating genes in the lipid synthesis pathway. Fatty acid oxidation, through effects on AMP-activated protein kinase (AMPK), adiponectin, peroxisome proliferator-activated receptors (PPARs), and mitochondrial function is predominantly altered in alcoholic liver disease, although studies suggest that activation of this pathway may improve nonalcoholic fatty liver disease. Finally, changes in fatty acid export, through effects on apolipoprotein B and microsomal transport protein are seen in both diseases. Thus, the similarities and differences in the mechanism of fat accumulation in the liver in nonalcoholic and alcoholic liver disease are explored in detail.
KEYWORDS
Lipid metabolism - hepatic steatosis - alcoholic fatty liver disease - nonalcoholic fatty liver disease - ER stress - sterol response element binding protein - peroxisome proliferator activated receptor - AMP-activated protein kinase
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David CrabbM.D.
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