Targeting ketone body metabolism to treat fatty liver disease

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a metabolic disorder marked by excessive accumulation of lipids within the liver. If untreated, this condition can progress to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and ultimately, hepatocellular carcinoma (HCC). Given the liver’s pivotal role in glucose and fatty acid metabolism, disruptions in these processes are commonly observed in MASLD. Ketone bodies, crucial energy metabolites primarily produced in the liver, are also closely related to the progression of MASLD. Recent studies have demonstrated that disrupted ketogenesis not only accompanies MASLD, but may also play a causal role in its development and progression. Moreover, activation of the ketogenic pathway has been suggested as a promising strategy for reducing excessive hepatic fat accumulation. This review focuses on the regulation of ketogenesis in MASLD, emphasizing the significance of dietary and pharmacological interventions as potential therapeutic approaches to treat fatty liver disease.