Folic acid attenuates high-fat diet-induced steatohepatitis via deacetylase SIRT1-dependent restoration of PPARα  

作　　者：Feng-Zhi Xin Ze-Hua Zhao Rui-Nan Zhang Qin Pan Zi-Zhen Gong Chao Sun Jian-Gao Fan 

机构地区：[1]Center for Fatty Liver,Department of Gastroenterology,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China [2]Shanghai Key Lab of Pediatric Gastroenterology and Nutrition,Shanghai 200092,China [3]Shanghai Institute for Pediatric Research,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China [4]Department of Pediatric Surgery,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China

出　　处：《World Journal of Gastroenterology》2020年第18期2203-2220,共18页世界胃肠病学杂志（英文版）

基　　金：Supported by National Key R&D Program of China,No.2017YFC0908903;National Natural Science Foundation of China,No.81873565,No.81470840,and No.81700503.

摘　　要：BACKGROUND Folic acid has been shown to improve non-alcoholic steatohepatitis(NASH),but its roles in hepatic lipid metabolism,hepatic one-carbon metabolism,and gut microbiota are still unknown.AIM To demonstrate the role of folic acid in lipid metabolism and gut microbiota in NASH.METHODS Twenty-four Sprague-Dawley rats were assigned into three groups:Chow diet,high-fat diet(HFD),and HFD with folic acid administration.At the end of 16 wk,the liver histology,the expression of hepatic genes related to lipid metabolism,one-carbon metabolism,and gut microbiota structure analysis of fecal samples based on 16 S r RNA sequencing were measured to evaluate the effect of folic acid.Palmitic acid-exposed Huh7 cell line was used to evaluate the role of folic acid in hepatic lipid metabolism.RESULTS Folic acid treatment attenuated steatosis,lobular inflammation,and hepatocellular ballooning in rats with HFD-induced steatohepatitis.Genes related to lipid de novo lipogenesis,β-oxidation,and lipid uptake were improvedin HFD-fed folic acid-treated rats.Furthermore,peroxisome proliferator-activated receptor alpha(PPARα)and silence information regulation factor 1(SIRT1)were restored by folic acid in HFD-fed rats and palmitic acid-exposed Huh7 cell line.The restoration of PPARαby folic acid was blocked after transfection with SIRT1 si RNA in the Huh7 cell line.Additionally,folic acid administration ameliorated depleted hepatic one-carbon metabolism and restored the diversity of the gut microbiota in rats with HFD-induced steatohepatitis.CONCLUSION Folic acid improves hepatic lipid metabolism by upregulating PPARαlevels via a SIRT1-dependent mechanism and restores hepatic one-carbon metabolism and diversity of gut microbiota,thereby attenuating HFD-induced NASH in rats.

关 键 词：Nonalcoholic fatty liver disease Folic acid Gut microbiota PPARΑ SIRT1 

分 类 号：R575.1[医药卫生—消化系统]