Adipose tissue inflammation contributes to short-term high-fat diet-induced hepatic insulin resistance

Am J Physiol Endocrinol Metab. 2013 Aug 1;305(3):E388-95. doi: 10.1152/ajpendo.00179.2013. Epub 2013 Jun 4.


High-fat feeding for 3-4 days impairs glucose tolerance and hepatic insulin sensitivity. However, it remains unclear whether the evolving hepatic insulin resistance is due to acute lipid overload or the result of induced adipose tissue inflammation and consequent dysfunctional adipose tissue-liver cross-talk. In the present study, feeding C57Bl6/J mice a fat-enriched diet [high-fat diet (HFD)] for 4 days induced glucose intolerance, hepatic insulin resistance (as assessed by hyperinsulinemic euglycemic clamp studies), and hepatic steatosis as well as adipose tissue inflammation (i.e., TNFα expression) compared with standard chow-fed mice. Adipocyte-specific depletion of the antiapoptotic/anti-inflammatory factor Fas (CD95) attenuated adipose tissue inflammation and improved glucose tolerance as well as hepatic insulin sensitivity without altering the level of hepatic steatosis induced by HFD. In summary, our results identify adipose tissue inflammation and resulting dysfunctional adipose tissue-liver cross-talk as an early event in the development of HFD-induced hepatic insulin resistance.

Keywords: adipose tissue-liver cross-talk; diabetes mellitus; lipotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / physiology
  • Adipose Tissue / physiopathology*
  • Animals
  • Area Under Curve
  • Blotting, Western
  • Cytokines / metabolism
  • Diet, High-Fat / adverse effects*
  • Dietary Fats / toxicity*
  • Exons / genetics
  • Fatty Acids, Nonesterified / blood
  • Fatty Liver / metabolism
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Inflammation / physiopathology*
  • Insulin / blood
  • Insulin Resistance / physiology*
  • Lipid Metabolism / drug effects
  • Liver / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA / biosynthesis
  • RNA / isolation & purification
  • Real-Time Polymerase Chain Reaction
  • Triglycerides / blood
  • fas Receptor / metabolism


  • Cytokines
  • Dietary Fats
  • Fatty Acids, Nonesterified
  • Insulin
  • Triglycerides
  • fas Receptor
  • RNA