This study compared the differences in adipose gene expression in subcutaneous (SC) and omental (OM) adipose tissue samples from nonobese (NO), insulin-sensitive obese (ISO), and insulin-resistant obese (IRO) subjects. Microarray analysis revealed that changes in adipose tissue insulin signalling gene expression were greater in OM than in SC tissue and were related to insulin resistance rather than to obesity, which was evaluated using body mass index. Study results suggested that adipose tissue from ISO subjects has a genetic profile similar to that of NO subjects and different from that of IRO subjects. Furthermore, insulin receptor and insulin receptor substrate-1 (IRS-1), which are central genes implicated in all insulin signalling pathways, were higher in IRO versus pooled insulin-sensitive (NO+ISO) subjects. Interestingly, negative regulators of IRS-1, Jnk and IKK, increased in the IRO state, supporting the hypothesis that these inflammation-related genes contribute to insulin resistance. Moreover, in addition to the increased expression levels of insulin receptor and IRS-1, the increase in GLUT-4 gene expression also suggests a compensatory mechanism. The data also showed that the expression of PPARgamma, CEBPbeta, and all of the protein synthesis pathways (mTor, Rheb, and 4EBP and eIF members) were down-regulated in IRO subjects. Overall, these results indicate that important changes in the expression levels of key genes of several insulin signalling pathways occur in OM adipose tissue with the development of insulin resistance rather than obesity. The authors concluded that additional evaluations among NO, ISO, and IRO populations are needed to better understand the changes that take place in the development of obesity when insulin resistance is not present as a confounding factor.
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