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Diabetologia. 2006 Sep;49(9):2162-73. Epub 2006 Jul 25.

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

Author information

1
INSERM, U680, Université Pierre et Marie Curie (UPMC-Paris 6), Faculty of Medicine, 27 rue Chaligny, 75012, Paris, France.

Abstract

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.

PMID:
16865359
DOI:
10.1007/s00125-006-0335-z
[Indexed for MEDLINE]

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