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Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation

文献类型：期刊论文

作者Xu, Yanhong1; Ye, Xiaotong2; Zhou, Yang2; Cao, Xinyu3; Peng, Shiqiao3; Peng, Yue4; Zhang, Xiaoying6; Sun, Yili5; Jiang, Haowen5; Huang, Wenying4
刊名FRONTIERS OF MEDICINE
出版日期2023-01-05
页码13
ISSN号2095-0217
关键词sodium butyrate succinylation HMGCS2 ketogenesis SIRT5
DOI10.1007/s11684-022-0943-0
通讯作者Ye, Jianping(yejianping@zzu.edu.cn)
英文摘要Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood beta-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down-and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD+/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
WOS关键词MITOCHONDRIA ; INSULIN ; BODIES ; SIRT5
资助项目National Key Research and Development Program of China ; Shanghai Association for Science and Technology ; [2018YFA0800603] ; [19ZR1439000]
WOS研究方向Oncology ; Research & Experimental Medicine
语种英语
出版者SPRINGER
WOS记录号WOS:000908570500001
源URL[http://119.78.100.183/handle/2S10ELR8/303899]  
专题新药研究国家重点实验室
通讯作者Ye, Jianping
作者单位1.Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Neurol Dept, Shanghai 201306, Peoples R China
2.Shanghai Ocean Univ, Natl Demonstrat Ctr Expt Fisheries Sci Educ, Shanghai 201306, Peoples R China
3.Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Shanghai Diabet Inst, Shanghai 200233, Peoples R China
4.Jiangxi Normal Univ, Sch Phys Educ, Nanchang 330022, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Zhengzhou Univ, Affiliated Zhengzhou Cent Hosp, Metab Dis Res Ctr, Zhengzhou 450007, Peoples R China
7.Zhengzhou Univ, Coll Med, Ctr Adv Med, Zhengzhou 450007, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Yanhong,Ye, Xiaotong,Zhou, Yang,et al. Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation[J]. FRONTIERS OF MEDICINE,2023:13.
APA Xu, Yanhong.,Ye, Xiaotong.,Zhou, Yang.,Cao, Xinyu.,Peng, Shiqiao.,...&Ye, Jianping.(2023).Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation.FRONTIERS OF MEDICINE,13.
MLA Xu, Yanhong,et al."Sodium butyrate activates HMGCS2 to promote ketone body production through SIRT5-mediated desuccinylation".FRONTIERS OF MEDICINE (2023):13.

入库方式： OAI收割

来源：上海药物研究所

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