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Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression.
- Source :
-
Antioxidants & redox signaling [Antioxid Redox Signal] 2012 Feb 01; Vol. 16 (3), pp. 229-43. Date of Electronic Publication: 2011 Oct 17. - Publication Year :
- 2012
-
Abstract
- Aims: Increased oxidative stress and mitochondrial dysfunction in obese adipocytes contribute to adipokine dysregulation, inflammation, and insulin resistance.<br />Results: Through an advanced proteomic analysis, we found that peroxiredoxin 3 (Prx3), a thioredoxin-dependent mitochondrial peroxidase, is highly expressed in 3T3-L1 adipocytes compared to preadipocytes. Interestingly, in obese db/db mice and human subjects, adipose Prx3 levels were significantly decreased, indicating its association with obesity. We therefore employed Prx3 knockout (KO) mice and transfected 3T3-L1 cells to examine the role of endogenous Prx3 in adipocyte metabolism. Prx3 KO mice had increased fat mass compared to wild-type due to adipocyte hypertrophy. Increased adipogenic transcription factors and lipogenic gene expression during differentiation of adipose tissue-derived stem cells from Prx3-deficient mice confirmed that these adipocytes are likely to accumulate fat. Mitochondrial protein carbonylation in Prx3 KO adipose tissue and mitochondrial superoxide level in Prx3 knockdown 3T3-L1 cells were increased showing aberrant regulation of oxidative stress. Proteomic analysis and gene expression analysis of Prx3 KO mice adipocytes also showed defect in mitochondria biogenesis along with enzymes involved in glucose/lipid metabolism and oxidative phosphorylation. In addition, expression level of adiponectin was downregulated and plasminogen activator inhibitor-1 was upregulated in Prx3 KO adipocytes. Impaired glucose tolerance and insulin resistance further implied metabolic dysregulation in Prx3 KO mice.<br />Innovation and Conclusion: These data suggest that endogenous Prx3 may play an essential role in maintaining normal characteristics of adipocytes and that defect in Prx3 alters mitochondrial redox state and function, and adipokine expression in adipocytes leading to metabolic alteration.
- Subjects :
- Adipocytes metabolism
Adipogenesis genetics
Adipokines genetics
Adipose Tissue, White cytology
Adipose Tissue, White metabolism
Adiposity
Animals
Blood Glucose
Cell Enlargement
Cells, Cultured
Gene Expression
Gene Expression Profiling
Gene Expression Regulation
Homeodomain Proteins metabolism
Lipid Metabolism
Male
Mice
Mice, Knockout
Mitochondrial Proteins metabolism
Peroxiredoxin III deficiency
Peroxiredoxin III genetics
Peroxiredoxins metabolism
Adipocytes physiology
Adipokines blood
Mitochondria metabolism
Oxidative Stress
Peroxiredoxin III metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1557-7716
- Volume :
- 16
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Antioxidants & redox signaling
- Publication Type :
- Academic Journal
- Accession number :
- 21902452
- Full Text :
- https://doi.org/10.1089/ars.2011.3952