Malonylation of Acetyl-CoA carboxylase 1 promotes hepatic steatosis and is attenuated by ketogenic diet in NAFLD

Cao, Huanyi1,2,3; Cai, Qingxian4; Guo, Wanrong1,2; Su, Qiao5; Qin, Hancheng1,2; Wang, Tian1,2; Xian, Yingxin1,2; Zeng, Longyi1,2; Cai, Mengyin1,2; Guan, Haixia; Chen, Sifan6,7; Liang, Hua1,2; Xu, Feng1,2

2023-04-25

10.1016/j.celrep.2023.112319

CELL REPORTS   Impact Factor & Quartile

2211-1247

Protein post-translational modifications (PTMs) participate in important bioactive regulatory processes and therefore can help elucidate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here, we investi-gate the involvement of PTMs in ketogenic diet (KD)-improved fatty liver by multi-omics and reveal a core target of lysine malonylation, acetyl-coenzyme A (CoA) carboxylase 1 (ACC1). ACC1 protein levels and Lys1523 malonylation are significantly decreased by KD. A malonylation-mimic mutant of ACC1 increases its enzyme activity and stability to promote hepatic steatosis, whereas the malonylation-null mutant upregu-lates the ubiquitination degradation of ACC1. A customized Lys1523ACC1 malonylation antibody confirms the increased malonylation of ACC1 in the NAFLD samples. Overall, the lysine malonylation of ACC1 is attenu-ated by KD in NAFLD and plays an important role in promoting hepatic steatosis. Malonylation is critical for ACC1 activity and stability, highlighting the anti-malonylation effect of ACC1 as a potential strategy for treating NAFLD.

SCI

English

Others

National Natural Science Foundation of China["81970741","82270942"] ; Local Innovative and Research Teams Projects of Guangdong Pearl River Talents Program[2017BT01S131] ; Science and Technology Program of Guangzhou[202102010229] ; Guangdong Basic and Applied Basic Research Founda-tion["2020A1515010226","2020A1515011245","2021B1515020005"] ; Guangdong Science and Technology Department["2020B1212060018","2020B1212030004"] ; Shenzhen Basic Research Project[JCYJ20210324130415040]

Cell Biology

Cell Biology

WOS:000998517500001

CELL PRESS

Web of Science

1.Sun Yat sen Univ, Affiliated Hosp 3, Dept Endocrinol & Metab, Guangzhou 510630, Peoples R China
2.Guangdong Prov Key Lab Diabetol, Guangzhou 510630, Peoples R China
3.Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Endocrinol, Guangzhou 510080, Peoples R China
4.Southern Univ Sci & Technol, Peoples Hosp Shenzhen 3, Dept Hepatopathy, Affiliated Hosp 2, Shenzhen 518112, Peoples R China
5.Sun Yat sen Univ, Affiliated Hosp 1, Anim Expt Ctr, Guangzhou 510080, Peoples R China
6.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangdong Hong Kong Joint Lab RNA Med, Guangzhou 510120, Guangdong, Peoples R China
7.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Med Res Ctr, Guangzhou 510120, Peoples R China

Cao, Huanyi,Cai, Qingxian,Guo, Wanrong,et al. Malonylation of Acetyl-CoA carboxylase 1 promotes hepatic steatosis and is attenuated by ketogenic diet in NAFLD[J]. CELL REPORTS,2023,42(4).

Cao, Huanyi.,Cai, Qingxian.,Guo, Wanrong.,Su, Qiao.,Qin, Hancheng.,...&Xu, Feng.(2023).Malonylation of Acetyl-CoA carboxylase 1 promotes hepatic steatosis and is attenuated by ketogenic diet in NAFLD.CELL REPORTS,42(4).

Cao, Huanyi,et al."Malonylation of Acetyl-CoA carboxylase 1 promotes hepatic steatosis and is attenuated by ketogenic diet in NAFLD".CELL REPORTS 42.4(2023).