Influence of obesity and insulin sensitivity on insulin signalling genes in human omental and subcutaneous adipose tissue

R. MacLaren, W. Cui, S. Simard, and K. Cianflone

Medicine, Laval University, Centre de Recherche, Quebec, Quebec G1V 4G5

Corresponding Author: katherine.cianflone{at}crhl.ulaval.ca

Obesity and insulin resistance are ndependent risk factors for metabolic syndrome, diabetes, and cardiovascular disease. Adipose tissue samples from non-obese(NO), obese insulin-sensitive (ISO), or obese insulin-resistant (IRO) subjects from subcutaneous (SC) and omental (OM) tissues (n=28) were analysed by microarray and confirmed by real time PCR. Changes in insulin-signalling gene expression were more pronounced in OM adipose tissue than SC, and related to insulin resistance rather than obesity, with few genes correlating with BMI. Insulin receptor and IRS1 were both increased in the IRO vs. pooled insulin sensitive (NO + ISO). In the glucose transport pathway, PI3Ka and PDK2 were decreased in IRO, while PI3K, Akt2, GLUT4 and GLUT1 were all increased. Jnk and IKK, regulators of IRS1, were increased in IRO (p< 0.01 and p<0.001 respectively). In the protein synthesis pathway, almost all genes examined were down-regulated in IRO including mTor, Rheb, and multiple members of the 4EBP and eIF families (all p<0.05 – 0.01). In the proliferation pathway SHC, SOS and Raf1 (p<0.05) were increased while Ras and MEK1/2 kinase 1 (p<0.05) were decreased in IRO. Finally, in the differentiation pathway PPAR, CEBPa and CEBPß were decreased whereas PPARd and CEBP and CEBPe were increased in IRO (p<0.05). Taken together, microarray and real-time PCR data demonstrate that it is insulin resistance rather than obesity that is associated with altered gene expression of insulin signalling genes, especially in omental adipose tissue.

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