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Dysregulation of adipose glutathione peroxidase 3 in obesity contributes to local and systemic oxidative stress

Cited 102 time in Web of Science Cited 106 time in Scopus
Authors
Lee, Yun Sok; Kim, A Young; Choi, Jin Woo; Kim, Min; Yasue, Shintaro; Son, Hee Jung; Masuzaki, Hiroaki; Park, Kyong Soo; Kim, Jae Bum
Issue Date
2008-06-20
Publisher
Endocrine Society
Citation
Mol Endocrinol. 2008 ;22(9):2176-89.
Keywords
3T3-L1 CellsAcetylcysteine/pharmacologyAdipose Tissue/drug effects/*enzymologyAnimalsAnoxia/enzymology/geneticsAntioxidants/pharmacologyBase SequenceGene Expression Regulation, Enzymologic/geneticsGlutathione Peroxidase/blood/*genetics/*metabolismHumansKidney/enzymologyLipopolysaccharides/pharmacologyLung/enzymologyMaleMiceMice, Inbred C57BLMice, ObeseObesity/blood/*enzymology/*geneticsOxidative StressPPAR gamma/metabolismRNA, Messenger/genetics/metabolismThiazolidinediones/pharmacologyTumor Necrosis Factor-alpha/pharmacology
Abstract
Glutathione peroxidase 3 (GPx3) accounts for the major antioxidant activity in the plasma. Here, we demonstrate that down-regulation of GPx3 in the plasma of obese subjects is associated with adipose GPx3 dysregulation, resulting from the increase of inflammatory signals and oxidative stress. Although GPx3 was abundantly expressed in kidney, lung, and adipose tissue, we observed that GPx3 expression was reduced selectively in the adipose tissue of several obese animal models as decreasing plasma GPx3 level. Adipose GPx3 expression was greatly suppressed by prooxidative conditions such as high levels of TNFalpha and hypoxia. In contrast, the antioxidant N-acetyl cysteine and the antidiabetic drug rosiglitazone increased adipose GPx3 expression in obese and diabetic db/db mice. Moreover, GPx3 overexpression in adipocytes improved high glucose-induced insulin resistance and attenuated inflammatory gene expression whereas GPx3 neutralization in adipocytes promoted expression of proinflammatory genes. Taken together, these data suggest that suppression of GPx3 expression in the adipose tissue of obese subjects might constitute a vicious cycle to expand local reactive oxygen species accumulation in adipose tissue potentially into systemic oxidative stress and obesity-related metabolic complications.
ISSN
0888-8809 (Print)
Language
English
URI
http://hdl.handle.net/10371/62370
DOI
https://doi.org/10.1210/me.2008-0023
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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