Nrf2 induces Ucp1 expression in adipocytes in response to β3-AR stimulation and enhances oxygen consumption in high-fat diet-fed obese mice.

Content Provider	Europe PMC
Author	Chang, Seo-Hyuk Jang, Jaeyool Oh, Seungjun Yoon, Jung-Hoon Jo, Dong-Gyu Yun, Ui Jeong Park, Kye Won
Copyright Year	2021
Abstract	Coldinduced norepinephrine activates β3-adrenergic receptors (β3-AR) to stimulate the kinase cascade and cAMP-response element-binding protein, leading to the induction of thermogenic gene expression including uncoupling protein 1 (Ucp1). Here, we showed that stimulation of the β3-AR by its agonists isoproterenol and CL316,243 in adipocytes increased the expression of Ucp1 and Heme Oxygenase 1 (Hmox1), the principal Nrf2 target gene, suggesting the functional interaction of Nrf2 with β3-AR signaling. The activation of Nrf2 by tert-butylhydroquinone and reactive oxygen species (ROS) production by glucose oxidase induced both Ucp1 and Hmox1 expression. The increased expression of Ucp1 and Hmox1 was significantly reduced in the presence of a Nrf2 chemical inhibitor or in Nrf2-deleted (knockout) adipocytes. Furthermore, Nrf2 directly activated the Ucp1 promoter, and this required DNA regions located at −3.7 and −2.0 kb of the transcription start site. The CL316,243-induced Ucp1 expression in adipocytes and oxygen consumption in obese mice were partly compromised in the absence of Nrf2 expression. These data provide additional insight into the role of Nrf2 in β3-AR-mediated Ucp1 expression and energy expenditure, further highlighting the utility of Nrf2-mediated thermogenic stimulation as a therapeutic approach to diet-induced obesity.
ISSN	19766696
Journal	BMB Reports
Volume Number	54
PubMed Central reference number	PMC8411042
Issue Number	8
PubMed reference number	33691909
e-ISSN	1976670X
DOI	10.5483/BMBRep.2021.54.8.023
Language	English
Publisher	Korean Society for Biochemistry and Molecular Biology
Publisher Date	2021-08-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2021 by the The Korean Society for Biochemistry and Molecular Biology
Subject Keyword	β3-adrenergic receptor Energy expenditure Nrf2 Obesity Uncoupling protein 1
Content Type	Text
Resource Type	Article
Subject	Medicine Molecular Biology Biochemistry