The Role of Carvedilol (CARV) in Improving Metabolic-Associated Fatty Liver Disease

Background/Objectives: Metabolic-associated fatty liver disease (MAFLD) has emerged as a significant global health concern, closely linked to metabolic syndrome and characterized by hepatic fat accumulation in the absence of excessive alcohol consumption. Carvedilol (CARV), a non-selective β-blocker, has long been used in the treatment of cardiovascular conditions, but emerging evidence suggests that it also exhibits metabolic regulatory properties, particularly in hepatic lipid metabolism. Apolipoprotein C3 (APOC3) is a key regulator of triglyceride metabolism and has been implicated in the development of hepatic steatosis. This research aimed to investigate the effects of carvedilol on hepatic lipid synthesis and the potential role of APOC3 downregulation in this process. Methods: Through a combination of in vivo and in vitro models. Results:we demonstrate that CARV significantly reduces hepatic lipid accumulation by downregulating APOC3 expression. Mechanistic assays revealed that CARV suppresses de novo lipogenesis and facilitates fatty acid β-oxidation by activating the AMPK signaling pathway in hepatocytes. In HFF-induced MAFLD mice, CARV ameliorated hepatic steatosis, liver injury, lobular inflammation and collagen deposition. Conclusions: Collectively, our findings identify a novel metabolic protective function of carvedilol, providing a potential therapeutic strategy for MAFLD and related metabolic diseases.