Adipose Deficiency of Nrf2 in ob/ob Mice Results in Severe Metabolic Syndrome
- Peng Xue1,
- Yongyong Hou1,
- Yanyan Chen1,2,
- Bei Yang1,3,
- Jingqi Fu1,
- Hongzhi Zheng1,2,
- Kathy Yarborough1,
- Courtney G. Woods1,
- Dianxin Liu4,
- Masayuki Yamamoto5,
- Qiang Zhang1,
- Melvin E. Andersen1 and
- Jingbo Pi1⇓
- 1Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina
- 2School of First Clinical Sciences, China Medical University, Shenyang, China
- 3College of Basic Medical Sciences, China Medical University, Shenyang, China
- 4Metabolic Signaling and Disease Program, Sanford-Burnham Medical Research Institute, Orlando, Florida
- 5Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan
- Corresponding author: Jingbo Pi,
P.X. and Y.H. contributed equally to this study.
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 β and peroxisome proliferator–activated receptor γ. 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 adipocyte-specific 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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0584/-/DC1.
- Received May 4, 2012.
- Accepted September 26, 2012.
- © 2013 by the American Diabetes Association.
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