Long-term treatment with interleukin-1beta induces insulin resistance in murine and human adipocytes.
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.
Lagathu
C
C
INSERM, U680, Université Pierre et Marie Curie (UPMC-Paris 6), Faculty of Medicine, 27 rue Chaligny, 75012, Paris, France.
Yvan-Charvet
L
L
Bastard
J-P
JP
Maachi
M
M
Quignard-Boulangé
A
A
Capeau
J
J
Caron
M
M
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
D052242:Adiponectin; D016207:Cytokines; D007328:Insulin; D053583:Interleukin-1beta; D005947:Glucose