Mechanisms and clinical implications of hepatocyte lipoapoptosis

Sophie C. Cazanave, Gregory J. Gores

Research output: Contribution to journalReview article

61 Scopus citations

Abstract

Nonalcoholic fatty liver disease (NAFLD) is characterized by insulin resistance, elevated serum levels of free fatty acids (FFAs) and fatty infiltration of the liver. Accumulation of triglycerides in the hepatocyte results from the uptake and esterification of circulating FFAs by the liver. Contrary to current theory, hepatic steatosis appears to be a detoxification process, as FFAs are directly cytotoxic for the hepatocyte and inhibition of triglyceride formation enhances FFAs toxicity. Hepatocyte apoptosis is a key feature of NAFLD and correlates with disease severity. Since FFA-induced toxicity, or lipoapoptosis, represents a mechanism for the pathogenesis of NAFLD, this article will highlight the cellular pathways contributing to hepatocyte lipoapoptosis. To date, there is no proven effective therapy for patients with NAFLD and insights into the molecular mediators of lipoapoptosis should help promote effective therapeutic strategies for this disease.

Original languageEnglish (US)
Pages (from-to)71-85
Number of pages15
JournalClinical Lipidology
Volume5
Issue number1
DOIs
StatePublished - Mar 8 2010

Keywords

  • BH3-only proteins
  • C-Jun N-terminal kinase
  • CCAAT/enhancer binding homologous protein
  • Death receptor
  • Endoplasmic reticulum stress
  • Hepatic steatosis
  • Nonalcoholic steatohepatitis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

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