Asprosin as a regulator of hepatic lipogenesis and its association with hepatic steatosis

Asprosin is a recently discovered adipokine involved in the regulation of hepatic gluconeogenesis and appetite, but its role in hepatic lipid metabolism, a key aspect of metabolic dysfunction-associated steatotic liver disease (MASLD), is unknown. This study aimed to investigate whether asprosin could regulate hepatic lipid metabolism in vitro and in an animal model and to determine the potential association between circulating levels of asprosin and the severity of hepatic steatosis in humans. The effects of asprosin on the metabolic phenotype of mice with diet-induced obesity (DIO), as well as on de novo lipogenesis, β-oxidation, and mitochondrial function, were analyzed in both cultured primary hepatocytes and mice by assessing mRNA and protein levels of metabolic pathway components, along with mitochondrial function. Furthermore, serum asprosin levels were measured in 314 subjects who also underwent transient elastography. The results showed that in vitro, asprosin reduced the expression of lipogenic genes and increased those of fatty acid oxidation and mitochondrial activity in hepatocytes. In the DIO model, asprosin-treated mice showed reduced lipid accumulation, improved metabolic parameters and increased abundance of proteins of lipid catabolism. Furthermore, asprosin levels were positively correlated with the controlled attenuation parameter (CAP) and liver stiffness (KPa) in FibroScan measurements. Higher asprosin levels were observed in subjects with severe steatosis (S2 and S3) compared to those without (S0). This adipokine appears to play a protective role in early hepatic steatosis by modulating lipid metabolism and enhancing mitochondrial function.