title: Influence of obesity and insulin sensitivity on insulin signaling genes in human omental and subcutaneous adipose tissue.
abstract: 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 = 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 (NO+ISO) subjects. In glucose transport, PI3Kalpha and PDK2 decreased in IRO subjects, whereas PI3Kgamma, 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, PPARgamma, CEBPalpha, and CEBPbeta decreased, whereas PPARdelta, CEBPgamma, and CEBPepsilon 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.
authors.affiliation: Experimental Medicine, McGill University Health Centre, Montreal, Canada.
authors.forename: R
authors.initials: R
authors.lastname: MacLaren
authors.forename: W
authors.initials: W
authors.lastname: Cui
authors.forename: S
authors.initials: S
authors.lastname: Simard
authors.forename: K
authors.initials: K
authors.lastname: Cianflone
mesh_terms: D000328:Adult; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D009852:Omentum / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D050151:Subcutaneous Fat / Q000378:metabolism*
chemical_list: D007328:Insulin