Interleukin-10 is a protective factor against diet-induced insulin resistance in liver

J Hepatol. 2008 Apr;48(4):628-37. doi: 10.1016/j.jhep.2007.12.017. Epub 2008 Jan 31.


Background/aims: The anti-inflammatory cytokine, interleukin-10 (IL-10), is known to exert a protective role in hepatic damage caused by viruses, alcohol, autoimmunity and a number of experimental aggressors. Recently, a protective role for IL-10 has also been proposed in diet-induced hepatic dysfunction. However, studies about the mechanisms involved in this process are controversial. The objective of this study was to evaluate the role of endogenous IL-10 in the development of hepatic insulin resistance, associated with diet-induced fatty liver disease.

Methods: Male Swiss mice treated for eight weeks with a high-fat diet became diabetic and developed non-alcoholic fatty liver disease, which is characterized by increased hepatic fat deposition and liver infiltration by F4/80 positive cells. This was accompanied by an increased hepatic expression of TNF-alpha, IL-6, IL-1beta and IL-10, and by an impaired insulin signal transduction through the insulin receptor/IRS1-IRS2/PI3-kinase/Akt/FOXO1 signaling pathway.

Results: Upon endogenous IL-10 inhibition for 5 days, using two distinct methods, a neutralizing anti-IL-10 antibody and an antisense oligonucleotide against IL-10, increased hepatic expression of the inflammatory markers TNF-alpha, IL-6, IL-1beta and F4/80 was observed. This was accompanied by a significant negative modulation of insulin signal transduction through insulin receptor/IRS1-IRS2/PI3-kinase/Akt/FOXO1, and by the stimulation of hepatic signaling proteins involved in gluconeogenesis and lipid synthesis.

Conclusions: Thus, in an animal model of diet-induced fatty liver disease, the inhibition of IL-10 promotes the increased expression of inflammatory cytokines, the worsening of insulin signaling and the activation of gluconeogenic and lipidogenic pathways.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology
  • Gene Expression
  • Glucose Tolerance Test
  • Immunoblotting
  • Immunoprecipitation
  • Insulin / blood
  • Insulin Resistance / physiology*
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Mice
  • Oligonucleotides, Antisense / pharmacology
  • RNA / genetics
  • Signal Transduction / genetics
  • Thionucleotides / pharmacology


  • Blood Glucose
  • Insulin
  • Oligonucleotides, Antisense
  • Thionucleotides
  • Interleukin-10
  • RNA