Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-α.
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.
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Expression of nuclear-encoded OXPHOS genes is down-regulated in visceral adipose tissue of humans with type 2 DM.
“In parallel, expression of nuclear-encoded OXPHOS genes is down-regulated in visceral adipose tissue of humans with type 2 DM (193).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [193]
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- Authors
- Dahlman, I., Forsgren, M., Sjögren, A., Nordström, E. A., Kaaman, M., Näslund, E., Attersand, A., & Arner, P.
- Affiliations
- Karolinska Institutet (SE)
- Swedish Orphan Biovitrum (Sweden) (SE)
- Biovitrum, Stockholm, Sweden
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
- Karolinska Institutet Danderyds Hospital, Stockholm, Sweden
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2006-06-01
- Volume
- 55
- Issue
- 6
- Pages
- 1792-1799
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2170103181
- Cited by
- 184
- References
- 41
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 5 · 2020: 8 · 2019: 13 · 2018: 7 · 2017: 11 · 2016: 11 · 2015: 11 · 2014: 12 · 2013: 10 · 2012: 10
- FWCI
- 8.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- type 2 diabetes, visceral adipose tissue, oxidative phosphorylation, TNF-α, insulin resistance, subcutaneous adipose tissue, obesity, fatty acid oxidation, preadipocyte differentiation, gene expression profiling
- MeSH terms
- Adult, Cells, Cultured, Diabetes Mellitus, Type 2, Electron Transport, Fatty Acids, Female, Humans, Middle Aged, Obesity, Oxidation-Reduction, Tumor Necrosis Factor-alpha, Down-Regulation, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Intra-Abdominal Fat
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