Macrophage metabolism impacts metabolic dysfunction-associated steatotic liver disease and its progression

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), with a progressive form of metabolic dysfunction-associated steatohepatitis (MASH), is the leading chronic liver disease worldwide, which can progress to advanced liver disease and hepatocellular carcinoma. MASLD is tightly associated with metabolic disorders such as obesity, insulin resistance, and type 2 diabetes. Macrophages, as an innate immune component and a linker of adaptive immune response, play important roles in the pathogenesis and treatment of MASLD or MASH. Metabolic reprogramming can regulate macrophage activation and polarization to inhibit MASLD or MASH progression to advanced liver disease. Here, we summarize the underlying mechanisms of how different metabolites such as amino acids, glucose, and fatty acids can regulate macrophage function and phenotype, the factors that regulate macrophage metabolism, and potential treatment options to regulate macrophage function in MASLD or MASH, as well as other associated metabolic disorders.