Long-term treatment with interleukin-1β induces insulin resistance in murine and human adipocytes
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).
IL1B inhibited insulin-induced phosphorylation of the insulin receptor β 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 γ and CCAAT/enhancer-binding protein α 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.
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.
- Long-term treatment with interleukin-1β induces insulin resistance in murine and human adipocytes
Volume 49, Issue 9 , pp 2162-2173
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- Adipose tissue
- Insulin signalling
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- Author Affiliations
- 1. INSERM, U680, Université Pierre et Marie Curie (UPMC-Paris 6), Faculty of Medicine, 27 rue Chaligny, 75012, Paris, France
- 3. INSERM, U671, Université Pierre et Marie Curie (UPMC-Paris 6), Institut des Cordeliers, Paris, France
- 2. Tenon Hospital, Department of Biochemistry and Hormonology, Paris, France