Role of metabolic lipases and lipolytic metabolites in the pathogenesis of NAFLD

Trends Endocrinol Metab. 2014 Nov;25(11):576-85. doi: 10.1016/j.tem.2014.08.001. Epub 2014 Aug 30.


Non-alcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease in Western countries, ranging from simple steatosis to steatohepatitis, cirrhosis, and hepatocellular cancer. Although the mechanisms underlying disease progression are incompletely understood, lipotoxic events in the liver resulting in inflammation and fibrosis appear to be central. Free fatty acids and their metabolites are potentially lipotoxic mediators triggering liver injury, suggesting a central role for metabolic lipases. These enzymes are major players in lipid partitioning between tissues and within cells, and provide ligands for nuclear receptors (NRs). We discuss the potential role of intracellular lipases and their lipolytic products in NAFLD. Because tissue-specific modulation of lipases is currently impossible, targeting NRs with ligands may open novel therapeutic perspectives.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Progression
  • Humans
  • Lipase / genetics
  • Lipase / physiology*
  • Lipolysis / physiology*
  • Liver / enzymology
  • Liver / metabolism
  • Non-alcoholic Fatty Liver Disease / enzymology
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Non-alcoholic Fatty Liver Disease / therapy
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Sterol Esterase / genetics


  • Receptors, Cytoplasmic and Nuclear
  • farnesoid X-activated receptor
  • Sterol Esterase
  • Lipase
  • PNPLA2 protein, human