ANGPTL3 orchestrates hepatic fructose sensing and metabolism

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to fructose metabolism, but the mechanisms of fructose uptake remains elusive.

In this study, the researchers identify Angiopoietin-like 3 (ANGPTL3) as a regulator of hepatic fructose metabolism in metabolic dysfunction-associated steatotic liver disease (MASLD), independent of its known role as an LPL inhibitor.

They also show that fructose exposure increases Circulating ANGPTL3 levels, consistent with an action as a fructose sensor.

Knocking down Angptl3 in the liver resulted in a significant reduction in the uptake of hepatic fructose metabolites and downregulation of the hepatic fructose transporter slc2a8 (GLUT8) and fructolysis enzymes.

https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00733-8

https://sciencemission.com/ANGPTL3--hepatic-fructose-sensing