Sodium Butyrate Supplementation Inhibits Hepatic Steatosis by Stimulating Liver Kinase B1 and Insulin-Induced GeneSummary

Ze-Hua Zhao; Zi-Xuan Wang; Da Zhou; Yamei Han; Fengguang Ma; Zhimin Hu; Feng-Zhi Xin; Xiao-Lin Liu; Tian-Yi Ren; Feifei Zhang; Yaqian Xue; Aoyuan Cui; Zhengshuai Liu; Jinyun Bai; Yuxiao Liu; Genxiang Cai; Weitong Su; Xiaozhen Dai; Feng Shen; Qin Pan; Yu Li; Jian-Gao Fan

Cellular and Molecular Gastroenterology and Hepatology (Jan 2021)

Sodium Butyrate Supplementation Inhibits Hepatic Steatosis by Stimulating Liver Kinase B1 and Insulin-Induced GeneSummary

Ze-Hua Zhao,
Zi-Xuan Wang,
Da Zhou,
Yamei Han,
Fengguang Ma,
Zhimin Hu,
Feng-Zhi Xin,
Xiao-Lin Liu,
Tian-Yi Ren,
Feifei Zhang,
Yaqian Xue,
Aoyuan Cui,
Zhengshuai Liu,
Jinyun Bai,
Yuxiao Liu,
Genxiang Cai,
Weitong Su,
Xiaozhen Dai,
Feng Shen,
Qin Pan,
Yu Li,
Jian-Gao Fan

Affiliations

Ze-Hua Zhao: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
Zi-Xuan Wang: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Da Zhou: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China
Yamei Han: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Fengguang Ma: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Zhimin Hu: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Feng-Zhi Xin: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Xiao-Lin Liu: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Tian-Yi Ren: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Feifei Zhang: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Yaqian Xue: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Aoyuan Cui: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Zhengshuai Liu: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Jinyun Bai: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
Yuxiao Liu: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Genxiang Cai: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Weitong Su: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
Xiaozhen Dai: School of Bioscience and Technology, Chengdu Medical College, Chengdu, China
Feng Shen: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Qin Pan: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yu Li: CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; Correspondence Address correspondence to Yu Li, PhD, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, 320 Yue Yang Road, Life Science Research Building A1816, Shanghai 200031, China.
Jian-Gao Fan: Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China; Jian-Gao Fan, PhD, Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, 1665 Kong Jiang Road, Shanghai 200092, China.

Journal volume & issue: Vol. 12, no. 3
pp. 857 – 871

Abstract

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Background and Aims: Butyric acid is an intestinal microbiota-produced short-chain fatty acid, which exerts salutary effects on alleviating nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism of butyrate on regulating hepatic lipid metabolism is largely unexplored. Methods: A mouse model of NAFLD was induced with high-fat diet feeding, and sodium butyrate (NaB) intervention was initiated at the eighth week and lasted for 8 weeks. Hepatic steatosis was evaluated and metabolic pathways concerning lipid homeostasis were analyzed. Results: Here, we report that administration of NaB by gavage once daily for 8 weeks causes an augmentation of insulin-induced gene (Insig) activity and inhibition of lipogenic gene in mice fed with high-fat diet. Mechanistically, NaB is sufficient to enhance the interaction between Insig and its upstream kinase AMP-activated protein kinase (AMPK). The stimulatory effects of NaB on Insig-1 activity are abolished in AMPKα1/α2 double knockout (AMPK−/−) mouse primary hepatocytes. Moreover, AMPK activation by NaB is mediated by LKB1, as evidenced by the observations showing NaB-mediated induction of phosphorylation of AMPK, and its downstream target acetyl-CoA carboxylase is diminished in LKB1–/– mouse embryonic fibroblasts. Conclusions: These studies indicate that NaB serves as a negative regulator of hepatic lipogenesis in NAFLD and that NaB attenuates hepatic steatosis and improves lipid profile and liver function largely through the activation of LKB1-AMPK-Insig signaling pathway. Therefore, NaB has therapeutic potential for treating NAFLD and related metabolic diseases.

Published in Cellular and Molecular Gastroenterology and Hepatology

ISSN: 2352-345X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/cellular-and-molecular-gastroenterology-and-hepatology/

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