Downregulation of Electron Transport Chain Genes in Visceral Adipose Tissue in Type 2 Diabetes Independent of Obesity and Possibly Involving Tumor Necrosis Factor-α
Autor: | Margaretha Forsgren, Elisabet Arvidsson Nordström, Maria Kaaman, Peter Arner, Erik Näslund, Annelie Sjögren, Ingrid Dahlman, Anneli Attersand |
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Rok vydání: | 2006 |
Předmět: |
Adult
medicine.medical_specialty FGF21 Intra-Abdominal Fat Endocrinology Diabetes and Metabolism Down-Regulation Adipose tissue Inflammation Type 2 diabetes Biology Electron Transport Insulin resistance Downregulation and upregulation Diabetes mellitus Internal medicine Internal Medicine medicine Humans Obesity Cells Cultured Oligonucleotide Array Sequence Analysis Tumor Necrosis Factor-alpha Gene Expression Profiling Fatty Acids Middle Aged medicine.disease Endocrinology Diabetes Mellitus Type 2 Female medicine.symptom Oxidation-Reduction |
Zdroj: | Diabetes. 55:1792-1799 |
ISSN: | 1939-327X 0012-1797 |
DOI: | 10.2337/db05-1421 |
Popis: | 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-α (TNF-α) is a major factor behind inflammation and insulin resistance in adipose tissue. TNF-α 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-α, suggesting that impaired oxidative phosphorylation of visceral adipose tissue has pathogenic importance for development of type 2 diabetes. |
Databáze: | OpenAIRE |
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