title: Long-term treatment with interleukin-1beta induces insulin resistance in murine and human adipocytes.
abstract: OBJECTIVE
  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.
  
  
  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
  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.
authors.affiliation: INSERM, U680, Université Pierre et Marie Curie (UPMC-Paris 6), Faculty of Medicine, 27 rue Chaligny, 75012, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Lagathu
authors.forename: L
authors.initials: L
authors.lastname: Yvan-Charvet
authors.forename: J-P
authors.initials: JP
authors.lastname: Bastard
authors.forename: M
authors.initials: M
authors.lastname: Maachi
authors.forename: A
authors.initials: A
authors.lastname: Quignard-Boulangé
authors.forename: J
authors.initials: J
authors.lastname: Capeau
authors.forename: M
authors.initials: M
authors.lastname: Caron
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D052242:Adiponectin; D016207:Cytokines; D007328:Insulin; D053583:Interleukin-1beta; D005947:Glucose