Short-chain fatty acids in nonalcoholic fatty liver disease: New prospects for short-chain fatty acids as therapeutic targets

Short-chain fatty acids in nonalcoholic fatty liver disease: New prospects for short-chain fatty acids as therapeutic targets

27 February 2024 | Xinyu Li, Maozhang He, Xinrui Yi, Xuejin Lu, Meizi Zhu, Min Xue, Yunshu Tang, Yaling Zhu
Short-chain fatty acids (SCFAs) are metabolites of gut microbiota (GM) that play a crucial role in alleviating nonalcoholic fatty liver disease (NAFLD). SCFAs, including acetate, propionate, and butyrate, regulate hepatic steatosis and inflammation through the gut-liver axis. This review summarizes the latest research on SCFAs in NAFLD up to November 2023, focusing on their production, function, and mechanisms of action in the gut-liver axis. SCFAs modulate genetic and epigenetic pathways, influencing lipid metabolism, inflammation, and liver function. They reduce cholesterol levels by inhibiting cholesterol synthesis, promoting bile acid production, and enhancing cholesterol efflux. SCFAs also induce autophagy to regulate hepatic steatosis and interact with G protein-coupled receptors (GPCRs) to modulate lipid metabolism and inflammation. Epigenetic mechanisms, including DNA methylation and histone modification, are also involved in SCFAs' protective effects on NAFLD. Prebiotics and clinical drugs that increase SCFAs levels show promise in improving NAFLD. The review highlights the potential of SCFAs as therapeutic targets for NAFLD, emphasizing the need for further research to explore their clinical applications and safety.Short-chain fatty acids (SCFAs) are metabolites of gut microbiota (GM) that play a crucial role in alleviating nonalcoholic fatty liver disease (NAFLD). SCFAs, including acetate, propionate, and butyrate, regulate hepatic steatosis and inflammation through the gut-liver axis. This review summarizes the latest research on SCFAs in NAFLD up to November 2023, focusing on their production, function, and mechanisms of action in the gut-liver axis. SCFAs modulate genetic and epigenetic pathways, influencing lipid metabolism, inflammation, and liver function. They reduce cholesterol levels by inhibiting cholesterol synthesis, promoting bile acid production, and enhancing cholesterol efflux. SCFAs also induce autophagy to regulate hepatic steatosis and interact with G protein-coupled receptors (GPCRs) to modulate lipid metabolism and inflammation. Epigenetic mechanisms, including DNA methylation and histone modification, are also involved in SCFAs' protective effects on NAFLD. Prebiotics and clinical drugs that increase SCFAs levels show promise in improving NAFLD. The review highlights the potential of SCFAs as therapeutic targets for NAFLD, emphasizing the need for further research to explore their clinical applications and safety.
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