Long-term treatment with interleukin-1beta induces insulin resistance in murine and human adipocytes

Diabetologia. 2006 Sep;49(9):2162-73. doi: 10.1007/s00125-006-0335-z. Epub 2006 Jul 25.


Aims/hypothesis: Adipose tissue inflammation has recently been implicated in the pathogenesis of insulin resistance and is probably linked to high local levels of cytokines. IL1B, a proinflammatory cytokine, may participate in this alteration.

Materials and methods: We evaluated the chronic effect (1-10 days) of IL1B (0.1-20 ng/ml) on insulin signalling in differentiating 3T3-F442A and differentiated 3T3-L1 murine adipocytes and in human adipocytes. We also assessed expression of the gene encoding IL1B in adipose tissue of wild-type and insulin-resistant mice (diet-induced and genetically obese ob/ob mice).

Results: IL1B inhibited insulin-induced phosphorylation of the insulin receptor beta subunit, insulin receptor substrate 1, Akt/protein kinase B and extracellular regulated kinase 1/2 in murine and human adipocytes. Accordingly, IL1B suppressed insulin-induced glucose transport and lipogenesis. Long-term treatment of adipose cells with IL1B decreased cellular lipid content. This could result from enhanced lipolysis and/or decreased expression of genes involved in lipid metabolism (acetyl-CoA carboxylase, fatty acid synthase). Down-regulation of peroxisome proliferating-activated receptor gamma and CCAAT/enhancer-binding protein alpha in response to IL1B may have contributed to the altered phenotype of IL1B-treated adipocytes. Moreover, IL1B altered adipocyte differentiation status in long-term cultures. IL1B also decreased the production of adiponectin, an adipocyte-specific protein that plays a positive role in insulin sensitivity. Expression of the gene encoding IL1B was increased in epididymal adipose tissue of obese insulin-resistant mice.

Conclusions/interpretation: IL1B is upregulated in adipose tissue of obese and insulin-resistant mouse models and may play an important role in the development of insulin resistance in murine and human adipose cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adiponectin / metabolism
  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Glucose / metabolism
  • Humans
  • Inflammation / metabolism
  • Insulin / pharmacology
  • Insulin Resistance*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors


  • Adiponectin
  • Cytokines
  • Insulin
  • Interleukin-1beta
  • Glucose