PhD defence Evi Johannes Caroline Koene

Keywords: Fructose, Ketohexokinase, Metabolic disorders

"Pharmacological inhibition of ketohexokinase in inborn and acquired metabolic disorders"

Fructose (fruit sugar) plays a role in inborn and acquired metabolic disorders. The breakdown of fructose in humans can be pharmacologically inhibited using a ketohexokinase (KHK) inhibitor. This thesis: 1) investigated whether KHK inhibition could be a potential new treatment for people with hereditary fructose intolerance (HFI); 2) used KHK inhibition to investigate the role of fructose in acquired metabolic disorders. The results of this thesis show, for the first time in humans, that pharmacological KHK inhibition may indeed be a potential treatment for people with HFI, as they did not get sick from fructose following treatment with this drug. Furthermore, the results of this thesis suggest that fructose contributes causally to the development of fatty liver disease, type 2 diabetes and elevated testosterone levels in women. This argues in favour of implementing measures to reduce fructose intake, such as improved information provision or a sugar tax

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