title: Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression.
abstract: OBJECTIVE
  Increased oxidative stress and mitochondrial dysfunction in obese adipocytes contribute to adipokine dysregulation, inflammation, and insulin resistance.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors: Joo Young
authors: JY
authors: Huh
authors: Yunghee
authors: Y
authors: Kim
authors: Jaeho
authors: J
authors: Jeong
authors: Jehyun
authors: J
authors: Park
authors: Inok
authors: I
authors: Kim
authors: Kyu Ha
authors: KH
authors: Huh
authors: Yu Seun
authors: YS
authors: Kim
authors: Hyun Ae
authors: HA
authors: Woo
authors: Sue Goo
authors: SG
authors: Rhee
authors: Kong-Joo
authors: KJ
authors: Lee
authors: Hunjoo
authors: H
authors: Ha
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis / Q000235:genetics; D054392:Adipokines / Q000097:blood* / Q000235:genetics; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D001786:Blood Glucose; D049108:Cell Enlargement; D002478:Cells, Cultured; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress; D061105:Peroxiredoxin III / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins / Q000378:metabolism
chemical_list: D054392:Adipokines; D001786:Blood Glucose; D018398:Homeodomain Proteins; D024101:Mitochondrial Proteins; C516116:Prdx3 protein, mouse; C489936:Prrx1 protein, mouse; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; C515975:Prdx5 protein, mouse