Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression

Joo Young Huh, Yunghee Kim, Jaeho Jeong, Jehyun Park, Inok Kim, Kyu Ha Huh, Yu Seun Kim, Hyun Ae Woo, Sue Goo Rhee, Kong Joo Lee, Hunjoo Ha

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Aims: 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. 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.

Original languageEnglish
Pages (from-to)229-243
Number of pages15
JournalAntioxidants and Redox Signaling
Volume16
Issue number3
DOIs
Publication statusPublished - 2012 Feb 1

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Peroxiredoxin III
Adipokines
Oxidative stress
Organelle Biogenesis
Adipocytes
Oxidative Stress
Molecules
Knockout Mice
3T3-L1 Cells
Gene expression
Proteomics
Insulin Resistance
Adipose Tissue
Fats
Protein Carbonylation
Insulin
Tissue
Gene Expression
Carbonylation
Glucose

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Huh, Joo Young ; Kim, Yunghee ; Jeong, Jaeho ; Park, Jehyun ; Kim, Inok ; Huh, Kyu Ha ; Kim, Yu Seun ; Woo, Hyun Ae ; Rhee, Sue Goo ; Lee, Kong Joo ; Ha, Hunjoo. / Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression. In: Antioxidants and Redox Signaling. 2012 ; Vol. 16, No. 3. pp. 229-243.
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Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression. / Huh, Joo Young; Kim, Yunghee; Jeong, Jaeho; Park, Jehyun; Kim, Inok; Huh, Kyu Ha; Kim, Yu Seun; Woo, Hyun Ae; Rhee, Sue Goo; Lee, Kong Joo; Ha, Hunjoo.

In: Antioxidants and Redox Signaling, Vol. 16, No. 3, 01.02.2012, p. 229-243.

Research output: Contribution to journalArticle

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AU - Huh, Joo Young

AU - Kim, Yunghee

AU - Jeong, Jaeho

AU - Park, Jehyun

AU - Kim, Inok

AU - Huh, Kyu Ha

AU - Kim, Yu Seun

AU - Woo, Hyun Ae

AU - Rhee, Sue Goo

AU - Lee, Kong Joo

AU - Ha, Hunjoo

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N2 - Aims: 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. 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.

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