Mitochondrial glycerol 3-phosphate dehydrogenase deficiency exacerbates lipotoxic cardiomyopathy

作者全名：Qu, Hua; Liu, Xiufei; Zhu, Jiaran; He, Niexia; He, Qingshan; Zhang, Linlin; Wang, Yuren; Gong, Xiaoli; Xiong, Xin; Liu, Jinbo; Wang, Chuan; Yang, Gangyi; Yang, Qingwu; Luo, Gang; Zhu, Zhiming; Zheng, Yi; Zheng, Hongting

作者地址：[Qu, Hua; Liu, Xiufei; Zhu, Jiaran; He, Qingshan; Zhang, Linlin; Wang, Yuren; Gong, Xiaoli; Xiong, Xin; Zheng, Yi; Zheng, Hongting] Army Med Univ, Affiliated Hosp 2, Translat Res Diabet Key Lab Chongqing Educ Commiss, Dept Endocrinol, Chongqing, Peoples R China; [He, Niexia] Army Med Univ, Dept Ultrasound, Affiliated Hosp 2, Chongqing, Peoples R China; [Liu, Jinbo; Wang, Chuan] Shandong Univ, Qilu Hosp, Dept Endocrinol, Jinan, Peoples R China; [Yang, Gangyi] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing, Peoples R China; [Yang, Qingwu] Army Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing 400037, Peoples R China; [Luo, Gang] Army Med Univ, Dept Orthoped, Affiliated Hosp 2, Chongqing 400037, Peoples R China; [Zhu, Zhiming] Army Med Univ, Affiliated Hosp 3, Dept Hypertens & Endocrinol, Chongqing, Peoples R China

通信作者：Qu, H; Zheng, Y; Zheng, HT (通讯作者)，Army Med Univ, Affiliated Hosp 2, Translat Res Diabet Key Lab Chongqing Educ Commiss, Dept Endocrinol, Chongqing, Peoples R China.

来源：ISCIENCE

ESI学科分类：　

WOS号：WOS:001244354000001

JCR分区：Q1

影响因子：4.6

年份：2024

卷号：27

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要：Metabolic diseases such as obesity and diabetes induce lipotoxic cardiomyopathy, which is characterized by myocardial lipid accumulation, dysfunction, hypertrophy, fibrosis and mitochondrial dysfunction. Here, we identify that mitochondrial glycerol 3 -phosphate dehydrogenase (mGPDH) is a pivotal regulator of cardiac fatty acid metabolism and function in the setting of lipotoxic cardiomyopathy. Cardiomyocytespecific deletion of mGPDH promotes high -fat diet induced cardiac dysfunction, pathological hypertrophy, myocardial fibrosis, and lipid accumulation. Mechanically, mGPDH deficiency inhibits the expression of desuccinylase SIRT5, and in turn, the hypersuccinylates majority of enzymes in the fatty acid oxidation (FAO) cycle and promotes the degradation of these enzymes. Moreover, manipulating SIRT5 abolishes the effects of mGPDH ablation or overexpression on cardiac function. Finally, restoration of mGPDH improves lipid accumulation and cardiomyopathy in both diet -induced and genetic obese mouse models. Thus, our study indicates that targeting mGPDH could be a promising strategy for lipotoxic cardiomyopathy in the context of obesity and diabetes.

基金机构：National Science Fund for Distinguished Young Scholars [81925007]; National Natural Science Foundation of China [82230025, 82070836, 82070881, 81970752, 82000769, 82100910]; Chongqing Distinguished Young Scholars [CSTB2022NSCQ-JQX0002]; National Science Fund for Excellent Young Scholars [82122013]; Talent Project of Army Medical University [2019R012, 2019R047, 2019XQYYYJ003-2]

基金资助正文：This work was supported by the National Science Fund for Distinguished Young Scholars (No. 81925007) and Excellent Young Scholars (82122013) , the National Natural Science Foundation of China (No. 82230025, No. 82070836, No. 82070881, No. 81970752, No. 82000769 and No. 82100910) , the Chongqing Distinguished Young Scholars (CSTB2022NSCQ-JQX0002) , and the "Talent Project" of Army Medical University (2019R012, 2019R047 and 2019XQYYYJ003-2) . BioRender was used to generate schematic figures.