The role of hepatic peroxisome proliferator-activated receptors (PPARs) in health and disease

Lynn Everett, Andrea Galli, David Crabb

Research output: Contribution to journalReview article

100 Scopus citations

Abstract

The liver has long been known to respond to exposure to certain chemicals with hyperplasia and proliferation of the peroxisomal compartment. This response is now known to be mediated by specific receptors. The peroxisome proliferator-activated receptors (PPARs) were cloned 10 years ago, and in that interval, have been found to serve as receptors for a number of endogenous lipid compounds, in addition to the peroxisome proliferators that originally led to their study. Three receptors, designated the α, δ, and γ receptors, have been found in mammals. PPARα is the most abundant form found in the liver, with smaller amounts of the δ and γ forms also expressed there. Kupffer cells, like other macrophages, appear to express the α and γ isoforms. Hepatic stellate cells are reported to express the γ isoform. PPARα knock-out mice fail to undergo peroxisome proliferation when challenged with the proliferators. Moreover, they have severe derangements of lipid metabolism, particularly during fasting, indicating that normal function of the alpha receptors is needed for lipid homeostasis. This in turn suggests that inadequate PPAR-mediated responses may contribute to abnormal fatty acid metabolism in alcoholic and non-alcoholic steatohepatitis. Recent information suggests that PPARγ receptors may be important in control of the activation state of the stellate cells, and their repression or inactivation may predispose to hepatic fibrosis. The first approved drug that specifically activates PPARγ, troglitazone, has rarely been found to cause serious liver injury. Although this is likely to represent an idiosyncratic reaction, the medical community will need to be alert to the possibility that activation or blockade of these receptors may cause hepatic dysfunction.

Original languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalLiver
Volume20
Issue number3
DOIs
StatePublished - Jun 21 2000

Keywords

  • Fatty acids
  • Liver injury
  • Metabolism
  • Peroxisome
  • Receptor
  • Steatohepatitis

ASJC Scopus subject areas

  • Hepatology

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