3-Hydroxybutyrate ameliorates insulin resistance by inhibiting PPARγSer273 phosphorylation in type 2 diabetic mice

作     者：Yudian Zhang Zihua Li Xinyi Liu Xinyu Chen Shujie Zhang Yuemeng Chen Jiangnan Chen Jin Chen Fuqing Wu Guo-Qiang Chen Yudian Zhang;Zihua Li;Xinyi Liu;Xinyu Chen;Shujie Zhang;Yuemeng Chen;Jiangnan Chen;Jin Chen;Fuqing Wu;Guo-Qiang Chen

作者机构：School of Life SciencesTsinghua UniversityBeijing100084P.R.China Department of Medical Genetics and Cell BiologySchool of Basic Medical Science of Ningxia Medical UniversityYinchuanNingxia750004P.R.China Center for Synthetic and Systems BiologyTsinghua UniversityBeijing100084China MOE Key Lab of Industrial BiocatalysisDept of Chemical EngineeringTsinghua UniversityBeijing100084P.R.China 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2023年第8卷第6期

页      面：3158-3167页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(Grant No.31870859)and Tsinghua Chunfeng Foundation 

主　　题：PPARγ thereby ketone 

摘      要：3-Hydroxybutyrate(3HB)is a small ketone body molecule produced endogenously by the body in the *** studies have shown that 3HB can reduce blood glucose level in type 2 diabetic(T2D)***,there is no systematic study and clear mechanism to evaluate and explain the hypoglycemic effect of *** we demonstrate that 3HB reduces fasting blood glucose level,improves glucose tolerance,and ameliorates insulin resistance in type 2 diabetic mice through hydroxycarboxylic acid receptor 2(HCAR2).Mechanistically,3HB increases intracellular calcium ion(Ca^(2+))levels by activating HCAR2,thereby stimulating adenylate cyclase(AC)to increase cyclic adenosine monophosphate(cAMP)concentration,and then activating protein kinase A(PKA).Activated PKA inhibits Raf1 proto-oncogene serine/threonine-protein kinase(Raf1)activity,resulting in a decrease in extracellular signal-regulated kinases 1/2(ERK1/2)activity and ultimately inhibiting peroxisome proliferator-activated receptorγ(PPARγ)Ser273 phosphorylation in *** of PPARγSer273 phosphorylation by 3HB altered the expression of PPARγregulated genes and reduced insulin ***,3HB ameliorates insulin resistance in type 2 diabetic mice through a pathway of HCAR2/Ca^(2+)/cAMP/PKA/Raf1/ERK1/2/PPARγ.