Pharmacologic inhibition of ketohexokinase prevents fructose-induced metabolic dysfunction.

ABSTRACT:

Objective

Recent studies suggest that excess dietary fructose contributes to metabolic dysfunction by promoting insulin resistance, de novo lipogenesis (DNL), and hepatic steatosis, thereby increasing the risk of obesity, type 2 diabetes (T2D), non-alcoholic steatohepatitis (NASH), and related comorbidities. Whether this metabolic dysfunction is driven by the excess dietary calories contained in fructose or whether fructose catabolism itself is uniquely pathogenic remains controversial. We sought to test whether a small molecule inhibitor of the primary fructose metabolizing enzyme ketohexokinase (KHK) can ameliorate the metabolic effects of fructose.

Methods

The KHK inhibitor PF-06835919 was used to block fructose metabolism in primary hepatocytes and Sprague Dawley rats fe

SUBMITTER: Gutierrez JA 

PROVIDER: S-EPMC8050029 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature