Hepatic metabolism and ketone production in metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is present in 25-35% of individuals in the United States. The purpose of this review is to provide the contextual framework for hepatic ketogenesis in MASLD and to spotlight recent advances that have improved our understanding of the mechanisms that drive its development and progression.

Traditionally, hepatic ketogenesis has only been considered metabolically during prolonged fasting/starvation or with carbohydrate deplete ketogenic diets where ketones provide important alternative energy sources. Over the past 2 years, it has become increasingly clear from preclinical rodent and human clinical studies that hepatic ketogenic insufficiency is a key contributor to the initiation and progression of MASLD.

A more thorough understanding of the metabolic dysregulation that occurs between the liver and extrahepatic tissues has significant potential in the development of innovative nutritional and pharmacological approaches to the treatment of MASLD.