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
Neutrophils are crucial for immunity and play important roles in inflammatory diseases;however,mouse models selectively deficient in neutrophils are limited,and neutrophil-specific diphtheria toxin(DT)-based depletion...Neutrophils are crucial for immunity and play important roles in inflammatory diseases;however,mouse models selectively deficient in neutrophils are limited,and neutrophil-specific diphtheria toxin(DT)-based depletion system has not yet been established.In this study,we generated a novel knock-in mouse model expressing diphtheria toxin receptor(DTR)under control of the endogenous Ly6G promoter.We showed that DTR expression was restricted to Ly6G+neutrophils and complete depletion of neutrophils could be achieved by DT treatment at 24-48 h intervals.We characterized the effects of specific neutrophil depletion in mice at steady-state,with acute inflammation and during tumor growth.Our study presents a valuable new tool to study the roles of neutrophils in the immune system and during tumor progression.展开更多
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.
基金funded by the National Natural Science Foundation of China(81471595 to YL,81601360 to LZ,U1904157 to LL)The animal model development was supported by 111 Program(D20036).
文摘Neutrophils are crucial for immunity and play important roles in inflammatory diseases;however,mouse models selectively deficient in neutrophils are limited,and neutrophil-specific diphtheria toxin(DT)-based depletion system has not yet been established.In this study,we generated a novel knock-in mouse model expressing diphtheria toxin receptor(DTR)under control of the endogenous Ly6G promoter.We showed that DTR expression was restricted to Ly6G+neutrophils and complete depletion of neutrophils could be achieved by DT treatment at 24-48 h intervals.We characterized the effects of specific neutrophil depletion in mice at steady-state,with acute inflammation and during tumor growth.Our study presents a valuable new tool to study the roles of neutrophils in the immune system and during tumor progression.
