NF-κB regulates brown adipocyte function through suppression of ANT2

The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-kappa B) is expressed in brown adipocytes, but its role remains largely unknown in the cells. This issue was addressed in current study by examining NF-kappa B in brown adipocytes in vitro and in vivo. NF-kappa B activity was increased by differentiation of brown adipocytes through elevation of p65 (RelA) expression. The transcriptional activity of NF-kappa B was induced by the cold stimulation with an elevation in 5276 phosphorylation of p65 protein. Inactivation of NF-kappa B 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-kappa B 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-kappa B inhibited expression of the adenine nucleotide translocase 2 (ANT2) in the control of apoptosis. Data suggest that NF-kappa B activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Automated summary

This study investigated the role of the transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-kappa B) in brown adipocytes. The findings showed that NF-kappa B activity increased during brown adipocyte differentiation and cold stimulation, protecting the cells from apoptosis by down-regulating the expression of adenine nucleotide translocase 2 (ANT2).