摘要
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-p65^(f/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.
基金
supported by the National Key R&D Program of China(No.2018YFA0800603)
a project of the Shanghai Association for Science and Technology(No.19ZR1439000,China)to Jianping Ye。
