The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis

Margaret S. Sozio, Suthat Liangpunsakul, David Crabb

Research output: Contribution to journalReview article

104 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)378-390
Number of pages13
JournalSeminars in Liver Disease
Volume30
Issue number4
DOIs
StatePublished - 2010

Keywords

  • alcoholic fatty liver disease
  • AMP-activated protein kinase
  • ER stress
  • hepatic steatosis
  • Lipid metabolism
  • nonalcoholic fatty liver disease
  • peroxisome proliferator activated receptor
  • sterol response element binding protein

ASJC Scopus subject areas

  • Hepatology

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