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Obesity and insulin resistance are independent risk factors for metabolic syndrome, diabetes, and cardiovascular disease. Adipose tissue samples from nonobese (NO), insulin-sensitive obese (ISO), and insulin-resistant obese (IRO) subjects from subcutaneous (SC) and omental (OM) adipose tissue (n 5 28) were analyzed by microarray and confirmed by real-time PCR. Insulin signaling gene expression changes were greater in OM than in SC tissue and were related to insulin resistance rather than to obesity; few genes correlated with body mass index. Insulin receptor and insulin receptor substrate 1 (IRS-1) increased in the IRO versus pooled insulin-sensitive (NO1ISO) subjects. In glucose transport, PI3Ka and PDK2 decreased in IRO subjects, whereas PI3Kg, Akt2, GLUT4, and GLUT1 increased. IRS-1 regulators Jnk and IKK increased in IRO (P , 0.01 and P , 0.001 respectively). In protein synthesis, most genes examined were downregulated in IRO subjects, including mTor, Rheb, and 4EBP and eIF members (all P , 0.05). In proliferation, SHC, SOS, and Raf1 (P , 0.05) were increased, whereas Ras and MEK1/2 kinase 1 (P , 0.05) were decreased, in IRO subjects. Finally, in differentiation, PPARg, CEBPa, and CEBPb decreased, whereas PPARd, CEBPg, and CEBP: increased, in IRO subjects (P , 0.05). Together, microarray and real-time PCR data demonstrate that insulin resistance rather than obesity is associated with altered gene expression of insulin signaling genes, especially in OM adipose tissue.-MacLaren, R., W. Cui, S. Simard, and K. Cianflone. Influence of obesity and insulin sensitivity on insulin signaling genes in human omental and subcutaneous adipose tissue. J. Lipid Res. Obesity and insulin resistance have both been identified as independent risk factors for metabolic syndrome, diabetes, and cardiovascular disease (1, 2). Many studies have focused on the physiologic parameters and genetic predisposition of subjects presenting with both obesity and insulin resistance (3). It was recently brought to attention, however, that subsets of obese individuals remain relatively insulin-sensitive (4-6). In the literature, they are referred to as insulin-sensitive obese (ISO) (7), metabolically healthy but obese (8), and metabolically normal but obese (9) subjects. For consistency, we use the term ISO throughout the present discussion. A number of studies have been conducted to identify physiologically different characteristics of the ISO population (10). In addition to insulin sensitivity, ISO subjects have lower plasma triglycerides and higher HDL cholesterol (9, 11). Shin et al. (12) determined that circulating C-reactive protein, interleukin 6, oxidized LDL, and visceral fat were lower in ISO compared with insulin-resistant obese (IRO) subjects. However, there are few data describing gene regulation that might account for this overall healthier status of ISO individuals.Adipose tissue is one of the key peripheral targets of insulin; acting as both an endocrine organ and an energy storage depot (13), it can affect whole-body ins...

In summary, while the mechanism of visfatin action remains to be elucidated, the clear effects of multiple hormones on visfatin expression support a physiological role.

BackgroundPrevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP) and Triglyceride (TG) (LAT) vs High ASP and TG (HAT). Subcutaneous (SC) and omental (OM) adipose tissues (n = 21) were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined.MethodsLAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1). ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p < 0.01 each). Differences between LAT and HAT group were almost exclusively in SC tissue, with little difference in OM tissue. Increased C5L2 (p < 0.01), an ASP receptor, in HAT suggests a compensatory ASP pathway, associated with increased TG storage.ResultsHAT adipose tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL), lipolysis (HSL, CES1, perilipin), fatty acid binding proteins (FABP1, FABP3) and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ). By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7). HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p < 0.025.ConclusionTaken together, the profile of C5L2 receptor, ASP gene expression and metabolic factors in adipose tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG.