Pirfenidone ameliorates liver steatosis by targeting the STAT3-SCD1 axis

作者全名："Yang, Shan; Zhang, Renzi; Deng, Wenzhen; Chang, Shichuan; Li, Yang; Li, Sheng"

作者地址："[Yang, Shan; Li, Yang] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing, Peoples R China; [Zhang, Renzi; Li, Sheng] Chongqing Med Univ, Affiliated Hosp 2, Dept Resp & Crit Care Med, Chongqing, Peoples R China; [Deng, Wenzhen] Qianjiang Cent Hosp Chongqing, Dept Endocrinol, Chongqing 409000, Peoples R China; [Chang, Shichuan] Chongqing Univ, Three Gorges Hosp, Oncol Dept, Chongqing 404000, Peoples R China"

通信作者："Li, Y (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing, Peoples R China.; Li, S (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Resp & Crit Care Med, Chongqing, Peoples R China."

来源：INFLAMMATION RESEARCH

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001057654800002

JCR分区：Q2

影响因子：4.8

年份：2023

卷号：72

期号：9

开始页：1773

结束页：1787

文献类型：Article

关键词：Pirfenidone; Hepatic steatosis; Metabolism-associated fatty liver disease; Stearoyl-CoA desaturase 1; Signal transducer and activator of transcription 3

摘要："ObjectivePrevious studies reported that pirfenidone (PFD) is associated with liver disease. However, the effects of pirfenidone on energy metabolism and hepatic lipid accumulation are still poorly understood.MethodsIn this study, C57BL/6J mice were randomly divided into two groups, and fed a normal chow diet (NCD) or a high-fat diet (HFD) for 16 weeks. At the end of the eighth week, half of the mice fed on both diets were treated with PFD. Biochemical and lipid metabolism-related indices were analyzed. Furthermore, Hepa 1-6 cells and mouse primary hepatocytes (MPHs) were incubated with PFD with or without free fatty acid (FFA) treatment. Then, stattic (a p-STAT3 inhibitor) or Ad-shSTAT3 was used to further elucidate the effects of Signal Transducer and Activator of Transcription 3 (STAT3) signaling on PFD regulation of hepatic steatosis.ResultsPFD ameliorated obesity and hepatic lipid deposition in HFD mice by decreasing stearoyl-CoA desaturase 1 (SCD1) expression and upregulating p-STAT3 in the liver. In Hepa 1-6 cells and MPHs, PFD also down-regulated the expression of SCD1. STAT3 inhibition treatment eliminated the benefits of PFD on both SCD1 and hepatic steatosis.ConclusionIn summary, our data reveal that PFD may play an important role in mitigating hepatic steatosis in a STAT3-SCD1-dependent manner."

基金机构：National Natural Science Foundation of China [82100824]; Chinese Postdoctoral Science Foundation [2021M700633]; China Endocrinology and Metabolism Young Scientific Talent Research Project [2021-N-03]; Postdoctoral Special Foundation of Chongqing [2022CQBSHTB3045]; Natural Science Foundation Project of CQ [cstc2021jcyj-msxmX0074]; Joint project of Chongqing Health Commission and Science and Technology Bureau [2020FYYX029]

基金资助正文："This study was supported by the National Natural Science Foundation of China (Grant no. 82100824), Chinese Postdoctoral Science Foundation (Grant no. 2021M700633), the China Endocrinology and Metabolism Young Scientific Talent Research Project (Grant no. 2021-N-03), Postdoctoral Special Foundation of Chongqing (2022CQBSHTB3045), the Natural Science Foundation Project of CQ (Grant no. cstc2021jcyj-msxmX0074), and Joint project of Chongqing Health Commission and Science and Technology Bureau (Grant no. 2020FYYX029)."