부산대학교 도서관

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic condition that affects nearly one billion people globally, characterized by triacylglycerol accumulation in the liver as a consequence of metabolic abnormalities (obesity and impaired glucose regulation). Low-grade inflammation, oxidative stress, mitochondrial dysfunction, and dysbiosis in gut microbiota are involved in the etiology of MAFLD, and both cardiovascular events and hepatic complications are the long-term consequences. In the absence of approved therapies for this condition, sodium–glucose cotransporter 2 inhibitors (SGLT-2 Is) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have the specific advantage of lowering body weight and providing cardiovascular benefits. Here, we discuss potential roles for SGLT-2 Is and GLP-1 RAs in the prevention and treatment of intrahepatic triacylglycerol accumulation and associated inflammation and/or fibrosis. MAFLD affects nearly one billion people globally and is fundamentally linked to cardiovascular diseases and hepatic outcomes, such as cirrhosis and hepatocellular cancer. Given that the term 'MAFLD' stresses a causal relationship between impaired glucose metabolism and the initiation and progression of fatty liver disease, it is reasonable to explore the potential therapeutic efficacy of glucose-lowering agents. There is preliminary evidence from clinical trials that SGLT-2 Is or GLP-1 RAs can reduce intrahepatic triacylglycerol accumulation and prevent progression of hepatic fibrosis. Given that neither SGLT-2 nor GLP-1 receptors are expressed in the liver, we identify indirect mechanisms interfering with the initiation and/or progression of MAFLD, specifically, to characterize the contribution of: weight loss and associated improvements in insulin sensitivity; adipokine- and cytokine-mediated anti-inflammatory, antifibrotic, and antioxidant effects; alterations in hepatic substrate supply (glucose and free fatty acids) and ketone body metabolism (SGLT-2 Is and GLP-1 RAs); and changes in microbiota (mainly GLP-1 RAs). Different modes of action suggest potential synergy between SGLT-2 Is and GLP-1 RAs in the prevention and treatment of MAFLD. [ABSTRACT FROM AUTHOR]