Endogenous interleukin-10 protects against hepatic steatosis but does not improve insulin sensitivity during high-fat feeding in mice

Endocrinology. 2006 Oct;147(10):4553-8. doi: 10.1210/en.2006-0417. Epub 2006 May 18.


Several studies have demonstrated an association in humans between plasma levels or production capacity of the antiinflammatory cytokine IL-10 and insulin sensitivity. The aim of our study was to investigate the protective role of endogenous IL-10 availability in the development of diet-induced insulin resistance. We compared parameters of glucose and lipid metabolism between IL-10(-/-) mice and wild-type (wt) mice fed a high-fat diet for 6 wk. This diet has previously been shown to induce steatosis and insulin resistance. After 6 wk on the high-fat diet, no differences in body weight, basal metabolism (measured by indirect calorimetry), or plasma levels of glucose, triglycerides, or cholesterol were observed between IL-10(-/-) and wt mice. Nonetheless, in IL-10(-/-) mice, plasma free fatty acid levels were 75% increased compared with wt mice after overnight fasting (P < 0.05). In addition, hepatic triglyceride content was 54% increased in IL-10(-/-) mice (P < 0.05). During a hyperinsulinemic euglycemic clamp, no differences were observed in whole-body or hepatic insulin sensitivity between both groups. We conclude that basal IL-10 production protects against hepatic steatosis but does not improve hepatic or whole-body insulin sensitivity, during high-fat feeding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / growth & development
  • Adipose Tissue / physiology
  • Animals
  • Blood Glucose / metabolism
  • Chromatography, Thin Layer
  • Diet
  • Dietary Fats / pharmacology*
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • Fibrinogen / metabolism
  • Genotype
  • Glucose / metabolism
  • Glucose Clamp Technique
  • Insulin Resistance / physiology*
  • Interleukin-10 / genetics
  • Interleukin-10 / physiology*
  • Lipid Metabolism / genetics
  • Lipids / blood
  • Liver Diseases / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Serum Amyloid A Protein / metabolism


  • Blood Glucose
  • Dietary Fats
  • Lipids
  • Serum Amyloid A Protein
  • Interleukin-10
  • Fibrinogen
  • Glucose