Essential fatty acids deficiency promotes lipogenic gene expression and hepatic steatosis through the liver X receptor

J Hepatol. 2013 May;58(5):984-92. doi: 10.1016/j.jhep.2013.01.006. Epub 2013 Jan 16.

Abstract

Background & aims: Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified.

Methods: We used wild type mice and mice lacking Liver X Receptors to perform a nutrigenomic study that aimed at examining the role of these transcription factors.

Results: We showed that, in the absence of Liver X Receptors, essential fatty acids deficiency does not promote steatosis. Consistent with this, Liver X Receptors are required for the elevated expression of genes involved in lipogenesis in response to essential fatty acids deficiency.

Conclusions: This work identifies, for the first time, the central role of Liver X Receptors in steatosis induced by essential fatty acids deficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholesterol / metabolism
  • Deficiency Diseases / physiopathology
  • Dietary Fats / pharmacology
  • Disease Models, Animal
  • Fatty Acids, Essential / deficiency*
  • Fatty Liver / physiopathology*
  • Female
  • Gene Expression / drug effects
  • Gene Expression / physiology*
  • Lipogenesis / drug effects
  • Lipogenesis / genetics*
  • Lipogenesis / physiology*
  • Liver / metabolism
  • Liver X Receptors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Orphan Nuclear Receptors / deficiency
  • Orphan Nuclear Receptors / genetics
  • Orphan Nuclear Receptors / physiology*
  • Transcription Factors / physiology
  • Triglycerides / metabolism
  • Up-Regulation / physiology

Substances

  • Dietary Fats
  • Fatty Acids, Essential
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Transcription Factors
  • Triglycerides
  • Cholesterol