Sodium Butyrate Supplementation Inhibits Hepatic Steatosis by Stimulating Liver Kinase B1 and Insulin-Induced Gene
| Autor: | Yuxiao Liu, Xiaozhen Dai, Xiao-Lin Liu, Aoyuan Cui, Feng Shen, Feng-Zhi Xin, Weitong Su, Jian-Gao Fan, Yamei Han, Ze-Hua Zhao, Feifei Zhang, Yaqian Xue, Yu Li, Genxiang Cai, Zhengshuai Liu, Zi-Xuan Wang, Qin Pan, Jinyun Bai, Zhimin Hu, Tian-Yi Ren, Fengguang Ma, Da Zhou |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine HFD high-fat diet Hepatic Lipogenesis RC799-869 ACC acetyl-CoA carboxylase AMP-Activated Protein Kinases GST glutathione S-transferase Mice chemistry.chemical_compound 0302 clinical medicine Non-alcoholic Fatty Liver Disease Nonalcoholic fatty liver disease Insulin Phosphorylation Insig insulin-induced gene Original Research Chemistry Kinase Gastroenterology Sodium butyrate Diseases of the digestive system. Gastroenterology 030211 gastroenterology & hepatology medicine.medical_specialty Insulin-Induced Gene LKB1 ATP adenosine triphosphate MAP Kinase Signaling System NaB sodium butyrate Butyrate Diet High-Fat Models Biological 03 medical and health sciences LKB1 liver kinase B1 NAFLD Internal medicine PYY peptide YY medicine Animals Humans GLP-1 glucagon-like peptide 1 Protein kinase A Hepatology Lipogenesis AMPK Lipid Metabolism medicine.disease Sodium Butyrate AMPK AMP-activated protein kinase Disease Models Animal 030104 developmental biology Endocrinology Gene Expression Regulation AMP adenosine monophosphate Dietary Supplements Hepatocytes Butyric Acid NAFLD nonalcoholic fatty liver disease Liver function Steatosis |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 3, Pp 857-871 (2021) |
| ISSN: | 2352-345X |
| Popis: | 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. Graphical abstract |
| Databáze: | OpenAIRE |
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