Original articles
Shiqiao Peng, Xiaoying Zhang, Lili Yu, Yanhong Xu, Yang Zhou, Shengnan Qian, Xinyu Cao, Xiaotong Ye, Jiajun Yang, Weiping Jia, Jianping Ye. NF-κB regulates brown adipocyte function through suppression of ANT2[J]. Acta Pharmaceutica Sinica B, 2022, 12(3): 1186-1197

NF-κB regulates brown adipocyte function through suppression of ANT2
Shiqiao Penga, Xiaoying Zhanga, Lili Yub, Yanhong Xuc, Yang Zhoud, Shengnan Qiana, Xinyu Caoa, Xiaotong Yed, Jiajun Yangc, Weiping Jiaa, Jianping Yea,e,f
a. Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China;
b. Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China;
c. Neurology Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China;
d. National Demonstration Center for Experimental Fisheries Science Education, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China;
e. Metabolic Disease Research Center, Zhengzhou University Affiliated Zhengzhou Central Hospital, Zhengzhou 450007, China;
f. Center for Advanced Medicine, College of Medicine, Zhengzhou University, Zhengzhou 450007, China
The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-κB) is expressed in brown adipocytes, but its role remains largely unknown in the cells. This issue was addressed in current study by examining NF-κB in brown adipocytes in vitro and in vivo. NF-κB activity was increased by differentiation of brown adipocytes through elevation of p65 (RelA) expression. The transcriptional activity of NF-κB was induced by the cold stimulation with an elevation in S276 phosphorylation of p65 protein. Inactivation of NF-κB in brown adipocytes made the knockout mice[uncoupling protein 1 (Ucp1)-CreER-p65f/f, U-p65-KO] intolerant to the cold environment. The brown adipocytes exhibited an increase in apoptosis, a decrease in cristae density and uncoupling activity in the interscapular brown adipose tissue (iBAT) of p65-KO mice. The alterations became severer after cold exposure of the KO mice. The brown adipocytes of mice with NF-κB activation (p65 overexpression, p65-OE) exhibited a set of opposite alterations with a reduction in apoptosis, an increase in cristae density and uncoupling activity. In mechanism, NF-κB inhibited expression of the adenine nucleotide translocase 2 (ANT2) in the control of apoptosis. Data suggest that NF-κB activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression.
Key words:    RelA    Mitochondria    Brown adipocyte    Energy metabolism    ANT2   
Received: 2021-09-15     Revised: 2021-10-05
DOI: 10.1016/j.apsb.2021.10.023
Funds: The project was supported by the National Key R&D Program of China (No. 2018YFA0800603) and a project of the Shanghai Association for Science and Technology (No. 19ZR1439000, China) to Jianping Ye.
Corresponding author: Jianping Ye,E-mai:yejianping@sjtu.edu.cn     Email:yejianping@sjtu.edu.cn
Author description:
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Shiqiao Peng
Xiaoying Zhang
Lili Yu
Yanhong Xu
Yang Zhou
Shengnan Qian
Xinyu Cao
Xiaotong Ye
Jiajun Yang
Weiping Jia
Jianping Ye

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