Impaired hepatic metabolism in Hereditary Fructose Intolerance confers fructose-independent risk for steatosis and hypertriglyceridemia.

ABSTRACT:

Objectives

Hereditary fructose intolerance (HFI), caused by Aldolase B deficiency, is a rare genetic disorder where fructose exposure leads to severe metabolic pathologies including Type-2 diabetes and liver steatosis. Despite adhering to fructose-free diets, some individuals still present with disease. Using a rat model of HFI we demonstrate that fructose independent pathologies exist and identify the molecular pathways driving disease.

Methods

Aldob was deleted in Sprague Dawley rats using CRIPSR/Cas9 (AldoB-KO). Phenotypic, metabolomic and transcriptomic studies were conducted to identify mechanisms promoting fructose-independent pathologies. Potential molecular causes were tested using pharmacologic inhibitors and ASOs.

Results

Deletion of Aldob caused hepatic ste

SUBMITTER: Fulham MA 

PROVIDER: S-EPMC12853781 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature