Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model

Sep 18, 2010Metabolism: clinical and experimental

How fat production and breakdown in the liver are controlled by adiponectin and insulin signaling in a fatty liver disease model

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Abstract

After 8 weeks on a high-fat and high-cholesterol diet, obese fa/fa Zucker rats exhibited significant changes in liver function related to nonalcoholic steatohepatitis (NASH).

  • Significant decreases in the expression levels of adiponectin receptors AdipoR1/R2 and IRS-2 were observed in the liver of NASH-afflicted rats.
  • In contrast, IRS-1 expression was significantly increased in these rats.
  • Lower expression of AdipoR1/R2 correlated with reduced activity of genes that inhibit fatty acid synthesis and promote fatty acid oxidation.
  • Increased levels of sterol regulatory element binding protein-1c indicated enhanced fatty acid synthesis due to the up-regulation of IRS-1.
  • An increase in forkhead box protein A2 was noted, which may relate to the down-regulation of IRS-2 and promote fatty acid oxidation.
  • The alterations in AdipoR and IRS expressions may play critical roles in the progression of NASH through their effects on fatty acid metabolism.

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