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

Feeding C57Bl6/J mice a high-fat diet for 4 days leads to impaired glucose tolerance and hepatic insulin resistance.

• High-fat diet induces glucose intolerance and hepatic insulin resistance as measured by hyperinsulinemic euglycemic clamp studies.
• Hepatic steatosis and increased adipose tissue inflammation, indicated by TNFα expression, occur after 4 days of high-fat feeding.
• Depleting the antiapoptotic factor Fas (CD95) in adipocytes reduces adipose tissue inflammation.
• Improved glucose tolerance and hepatic insulin sensitivity is observed with adipocyte-specific Fas depletion, despite unchanged hepatic steatosis levels.
• Adipose tissue inflammation and dysfunctional communication with the liver may be early contributors to the development of hepatic insulin resistance from high-fat diets.

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