Adipose deficiency of Nrf2 in ob/ob mice results in severe metabolic syndrome

Peng Xue, Yongyong Hou, Yanyan Chen, Bei Yang, Jingqi Fu, Hongzhi Zheng, Kathy Yarborough, Courtney G. Woods, Dianxin Liu, Masayuki Yamamoto, Qiang Zhang, Melvin E. Andersen, Jingbo Pi

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82 Citations (Scopus)

Abstract

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that functions as a master regulator of the cellular adaptive response to oxidative stress. Our previous studies showed that Nrf2 plays a critical role in adipogenesis by regulating expression of CCAAT/enhancer-binding protein b and peroxisome proliferator- activated receptor g. To determine the role of Nrf2 in the development of obesity and associated metabolic disorders, the incidence of metabolic syndrome was assessed in whole-body or adipocytespecific Nrf2-knockout mice on a leptin-deficient ob/ob background, a model with an extremely positive energy balance. On the ob/ob background, ablation of Nrf2, globally or specifically in adipocytes, led to reduced white adipose tissue (WAT) mass, but resulted in an even more severe metabolic syndrome with aggravated insulin resistance, hyperglycemia, and hypertriglyceridemia. Compared with wild-type mice, WAT of ob/ob mice expressed substantially higher levels of many genes related to antioxidant response, inflammation, adipogenesis, lipogenesis, glucose uptake, and lipid transport. Absence of Nrf2 in WAT resulted in reduced expression of most of these factors at mRNA or protein levels. Our findings support a novel role for Nrf2 in regulating adipose development and function, by which Nrf2 controls the capacity of WAT expansion and insulin sensitivity and maintains glucose and lipid homeostasis.

Original languageEnglish
Pages (from-to)845-854
Number of pages10
JournalDiabetes
Volume62
Issue number3
DOIs
Publication statusPublished - 2013 Mar 1
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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  • Cite this

    Xue, P., Hou, Y., Chen, Y., Yang, B., Fu, J., Zheng, H., Yarborough, K., Woods, C. G., Liu, D., Yamamoto, M., Zhang, Q., Andersen, M. E., & Pi, J. (2013). Adipose deficiency of Nrf2 in ob/ob mice results in severe metabolic syndrome. Diabetes, 62(3), 845-854. https://doi.org/10.2337/db12-0584