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J Biol Chem. 2016 Apr 1;291(14):7754-66. doi: 10.1074/jbc.M115.673756. Epub 2016 Feb 3.

Increased Energy Expenditure, Ucp1 Expression, and Resistance to Diet-induced Obesity in Mice Lacking Nuclear Factor-Erythroid-2-related Transcription Factor-2 (Nrf2).

Author information

1
From the Department of Laboratory Medicine and Pathology and.
2
the Department of Psychiatry and Human Behavior, University of California, Irvine, California 92697 and.
3
the Department of Laboratory Medicine, University of California, San Francisco, California 94107.
4
From the Department of Laboratory Medicine and Pathology and jchan@uci.edu.

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.

KEYWORDS:

adipose tissue; antioxidant; oxidative stress; reactive oxygen species (ROS); uncoupling protein

PMID:
26841864
PMCID:
PMC4817199
DOI:
10.1074/jbc.M115.673756
[Indexed for MEDLINE]
Free PMC Article

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