Ketohexokinase inhibition improves NASH by reducing fructose-induced steatosis and fibrogenesis.

ABSTRACT:

Background & aims

Increasing evidence highlights dietary fructose as a major driver of non-alcoholic fatty liver disease (NAFLD) pathogenesis, the majority of which is cleared on first pass through the hepatic circulation by enzymatic phosphorylation to fructose-1-phosphate via the ketohexokinase (KHK) enzyme. Without a current approved therapy, disease management emphasises lifestyle interventions, but few patients adhere to such strategies. New targeted therapies are urgently required.

Methods

We have used a unique combination of human liver specimens, a murine dietary model of NAFLD and human multicellular co-culture systems to understand the hepatocellular consequences of fructose administration. We have also performed a detailed nuclear magnetic resonance-based metaboli

SUBMITTER: Shepherd EL 

PROVIDER: S-EPMC7807164 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature