PMID- 16731844 OWN - NLM STAT- MEDLINE DCOM- 20070723 LR - 20060529 IS - 0012-1797 (Print) IS - 0012-1797 (Linking) VI - 55 IP - 6 DP - 2006 Jun TI - Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-alpha. PG - 1792-9 AB - 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. FAU - Dahlman, Ingrid AU - Dahlman I AD - Department of Medicine, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden. FAU - Forsgren, Margaretha AU - Forsgren M FAU - Sjogren, Annelie AU - Sjogren A FAU - Nordstrom, Elisabet Arvidsson AU - Nordstrom EA FAU - Kaaman, Maria AU - Kaaman M FAU - Naslund, Erik AU - Naslund E FAU - Attersand, Anneli AU - Attersand A FAU - Arner, Peter AU - Arner P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - 0 (Fatty Acids) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adult MH - Cells, Cultured MH - Diabetes Mellitus, Type 2/*genetics/metabolism MH - Down-Regulation/drug effects MH - Electron Transport/genetics MH - Fatty Acids/metabolism MH - Female MH - *Gene Expression Profiling MH - Humans MH - Intra-Abdominal Fat/drug effects/*metabolism MH - Middle Aged MH - Obesity/*genetics MH - Oligonucleotide Array Sequence Analysis MH - Oxidation-Reduction/drug effects MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 2006/05/30 09:00 MHDA- 2007/07/24 09:00 CRDT- 2006/05/30 09:00 PHST- 2006/05/30 09:00 [pubmed] PHST- 2007/07/24 09:00 [medline] PHST- 2006/05/30 09:00 [entrez] AID - 55/6/1792 [pii] AID - 10.2337/db05-1421 [doi] PST - ppublish SO - Diabetes. 2006 Jun;55(6):1792-9. doi: 10.2337/db05-1421.