title: Increased Energy Expenditure, Ucp1 Expression, and Resistance to Diet-induced Obesity in Mice Lacking Nuclear Factor-Erythroid-2-related Transcription Factor-2 (Nrf2).
abstract: The NRF2 (also known as NFE2L2) transcription factor is a critical regulator of genes involved in defense against oxidative stress. Previous studies suggest thatNrf2plays a role in adipogenesisin vitro, and deletion of theNrf2gene protects against diet-induced obesity in mice. Here, we demonstrate that resistance to diet-induced obesity inNrf2(-/-)mice is associated with a 20-30% increase in energy expenditure. Analysis of bioenergetics revealed thatNrf2(-/-)white adipose tissues exhibit greater oxygen consumption. White adipose tissue showed a >2-fold increase inUcp1gene expression. Oxygen consumption is also increased nearly 2.5-fold inNrf2-deficient fibroblasts. Oxidative stress induced by glucose oxidase resulted in increasedUcp1expression. Conversely, antioxidant chemicals (such asN-acetylcysteine and Mn(III)tetrakis(4-benzoic acid)porphyrin chloride) and SB203580 (a known suppressor ofUcp1expression) decreasedUcp1and oxygen consumption inNrf2-deficient fibroblasts. These findings suggest that increasing oxidative stress by limitingNrf2function in white adipocytes may be a novel means to modulate energy balance as a treatment of obesity and related clinical disorders.
authors: From the Department of Laboratory Medicine and Pathology and.
authors: Kevin
authors: K
authors: Schneider
authors: From the Department of Laboratory Medicine and Pathology and.
authors: Joshua
authors: J
authors: Valdez
authors: From the Department of Laboratory Medicine and Pathology and.
authors: Janice
authors: J
authors: Nguyen
authors: the Department of Psychiatry and Human Behavior, University of California, Irvine, California 92697 and.
authors: Marquis
authors: M
authors: Vawter
authors: the Department of Psychiatry and Human Behavior, University of California, Irvine, California 92697 and.
authors: Brandi
authors: B
authors: Galke
authors: the Department of Laboratory Medicine, University of California, San Francisco, California 94107.
authors: Theodore W
authors: TW
authors: Kurtz
authors: From the Department of Laboratory Medicine and Pathology and jchan@uci.edu.
authors: Jefferson Y
authors: JY
authors: Chan
mesh_terms: D050156:Adipogenesis; D000818:Animals; D004032:Diet / Q000009:adverse effects; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation; D007473:Ion Channels / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000172:deficiency*; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000187:drug effects; D000071256:Uncoupling Protein 1
chemical_list: D016166:Free Radical Scavengers; D007473:Ion Channels; D024101:Mitochondrial Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1
keywords: adipose tissue; antioxidant; oxidative stress; reactive oxygen species (ROS); uncoupling protein