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Deficiency of NPGPx, an oxidative stress sensor, leads to obesity in mice and human.


ABSTRACT: Elevated oxidative stress is closely associated with obesity. Emerging evidence shows that instead of being a consequence of obesity, oxidative stress may also contribute to fat formation. Nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) is a conserved oxidative stress sensor/transducer and deficiency of NPGPx causes accumulation of reactive oxygen species (ROS). In this communication, we show that NPGPx was highly expressed in preadipocytes of adipose tissue. Deficiency of NPGPx promoted preadipocytes to differentiate to adipocytes via ROS-dependent dimerization of protein kinase A regulatory subunits and activation of CCAAT/enhancer-binding protein beta (C/EBP?). This enhanced adipogenesis was alleviated by antioxidant N-acetylcysteine (NAC). Consistently, NPGPx-deficient mice exhibited markedly increased fat mass and adipocyte hypertrophy, while treatment with NAC ablated these phenotypes. Furthermore, single nucleotide polymorphisms (SNPs) in human NPGPx gene, which correlated with lower NPGPx expression level in adipose tissue, were associated with higher body mass index (BMI) in several independent human populations. These results indicate that NPGPx protects against fat accumulation in mice and human via modulating ROS, and highlight the importance of targeting redox homeostasis in obesity management.

SUBMITTER: Chang YC 

PROVIDER: S-EPMC3944459 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Deficiency of NPGPx, an oxidative stress sensor, leads to obesity in mice and human.

Chang Yi-Cheng YC   Yu Yu-Hsiang YH   Shew Jin-Yuh JY   Lee Wei-Jei WJ   Hwang Juey-Jen JJ   Chen Yen-Hui YH   Chen Yet-Ran YR   Wei Pei-Chi PC   Chuang Lee-Ming LM   Lee Wen-Hwa WH  

EMBO molecular medicine 20130704 8


Elevated oxidative stress is closely associated with obesity. Emerging evidence shows that instead of being a consequence of obesity, oxidative stress may also contribute to fat formation. Nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) is a conserved oxidative stress sensor/transducer and deficiency of NPGPx causes accumulation of reactive oxygen species (ROS). In this communication, we show that NPGPx was highly expressed in preadipocytes of adipose tissu  ...[more]

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