Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction

•PF-06835919 is a potent inhibitor of fructose metabolism in rats and humans.•Rats fed fructose at levels consistent with the typical American diet develop hyperinsulinemia, hyperlipidemia and steatosis.•KHK inhibition reverses fructose-induced metabolic dysfunction by blocking ChREBP activation.•Due to the global dietary prevalence of fructose, KHK inhibition is a potential pharmacotherapy for metabolic diseases.