title: Adipose deficiency of Nrf2 in ob/ob mice results in severe metabolic syndrome.
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 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.
authors.affiliation: Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Xue
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Hou
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Chen
authors.forename: Bei
authors.initials: B
authors.lastname: Yang
authors.forename: Jingqi
authors.initials: J
authors.lastname: Fu
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Zheng
authors.forename: Kathy
authors.initials: K
authors.lastname: Yarborough
authors.forename: Courtney G
authors.initials: CG
authors.lastname: Woods
authors.forename: Dianxin
authors.initials: D
authors.lastname: Liu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
authors.forename: Jingbo
authors.initials: J
authors.lastname: Pi
mesh_terms: D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology; D050154:Adiposity; D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006943:Hyperglycemia / Q000209:etiology; D015228:Hypertriglyceridemia / Q000209:etiology; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000150:complications*; D009928:Organ Specificity; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012333:RNA, Messenger