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 ...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.展开更多
IF1(ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F1Fo-ATP synthase to control ATP production.IF1 activity remains unknown in the regulation of GLP-1 activity.In this study...IF1(ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F1Fo-ATP synthase to control ATP production.IF1 activity remains unknown in the regulation of GLP-1 activity.In this study,IF1 was examined in the diet-induced obese mice using the gene knockout(If1-KO) mice.The mice gained more body weight on a high fat diet without a change in food intake.Insulin tolerance was impaired,but the oral glucose tolerance was improved through an increase in GLP-1 secretion.The KO mice exhibited an improved intestine structure,mitochondrial superstructure,enhanced mitophagy,reduced apoptosis and decreased adenine nucleotide translocase 2(ANT2) protein in the intestinal epithelial cells together with preserved gut microbiota.The data suggest that GLP-1 secretion was enhanced in the obese If1-KO mice to preserve glucose tolerance through a signaling pathway of ANT2/mitochondria/L-cells/GLP-1/insulin.IF1 is a potential mitochondrial target for induction of GLP-1 secretion in L-cells.展开更多
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。
文摘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funded by a project of the National Key Research and Development Program of China(2018YFA0800603)to Jianping Yethe 111 Project(D20036,China)to Hui Wang+2 种基金the National Natural Science Foundation-Henan Union grant of China(U1901131)to Genshen Zhongthe Training Program for Excellent Young Teachers in Higher Education of Henan Province(2017GGJS110,China)to Xiwen Xiongthe Health Commission of Henan Province(LHGJ20190497,China)to Yaya Guan。
文摘IF1(ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F1Fo-ATP synthase to control ATP production.IF1 activity remains unknown in the regulation of GLP-1 activity.In this study,IF1 was examined in the diet-induced obese mice using the gene knockout(If1-KO) mice.The mice gained more body weight on a high fat diet without a change in food intake.Insulin tolerance was impaired,but the oral glucose tolerance was improved through an increase in GLP-1 secretion.The KO mice exhibited an improved intestine structure,mitochondrial superstructure,enhanced mitophagy,reduced apoptosis and decreased adenine nucleotide translocase 2(ANT2) protein in the intestinal epithelial cells together with preserved gut microbiota.The data suggest that GLP-1 secretion was enhanced in the obese If1-KO mice to preserve glucose tolerance through a signaling pathway of ANT2/mitochondria/L-cells/GLP-1/insulin.IF1 is a potential mitochondrial target for induction of GLP-1 secretion in L-cells.
