title: Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-alpha.
abstract: Impaired oxidative phosphorylation is suggested as a factor behind insulin resistance of skeletal muscle in type 2 diabetes. The role of oxidative phosphorylation in adipose tissue was elucidated from results of Affymetrix gene profiling in subcutaneous and visceral adipose tissue of eight nonobese healthy, eight obese healthy, and eight obese type 2 diabetic women. Downregulation of several genes in the electron transport chain was the most prominent finding in visceral fat of type 2 diabetic women independent of obesity, but the gene pattern was distinct from that previously reported in skeletal muscle in type 2 diabetes. A similar but much weaker effect was observed in subcutaneous fat. Tumor necrosis factor-alpha (TNF-alpha) is a major factor behind inflammation and insulin resistance in adipose tissue. TNF-alpha treatment decreased mRNA expression of electron transport chain genes and also inhibited fatty acid oxidation when differentiated human preadipocytes were treated with the cytokine for 48 h. Thus, type 2 diabetes is associated with a tissue- and region-specific downregulation of oxidative phosphorylation genes that is independent of obesity and at least in part mediated by TNF-alpha, suggesting that impaired oxidative phosphorylation of visceral adipose tissue has pathogenic importance for development of type 2 diabetes.
authors.affiliation: Department of Medicine, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.forename: Margaretha
authors.initials: M
authors.lastname: Forsgren
authors.forename: Annelie
authors.initials: A
authors.lastname: Sjögren
authors.forename: Elisabet Arvidsson
authors.initials: EA
authors.lastname: Nordström
authors.forename: Maria
authors.initials: M
authors.lastname: Kaaman
authors.forename: Erik
authors.initials: E
authors.lastname: Näslund
authors.forename: Anneli
authors.initials: A
authors.lastname: Attersand
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004579:Electron Transport / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D014409:Tumor Necrosis Factor-alpha