Fructose metabolism in the liver: Enzymatic pathways, de novo lipogenesis induction, and implications for non-alcoholic fatty liver disease

Abstract

Excessive fructose consumption has emerged as a significant contributor to non-alcoholic fatty liver disease through mechanisms distinct from other dietary sugars. This research investigated the hepatic metabolic responses to fructose exposure, focusing on de novo lipogenesis pathway activation and lipid accumulation patterns. Adult participants (n=168) were recruited from the Osaka Institute of Liver Sciences between March 2023 and September 2024, including individuals with established NAFLD (n=94) and metabolically healthy controls (n=74). Dietary fructose intake was quantified using validated food frequency questionnaires and 24-hour dietary recalls. Hepatic lipid content was measured using proton magnetic resonance spectroscopy. De novo lipogenesis rates were determined through stable isotope tracer methodology using deuterated water incorporation. Results demonstrated positive correlation between fructose intake and hepatic triglyceride content (r=0.68, p