There is increasing evidence that either ingested or produced
fructose may have a role in
metabolic syndrome. While not commonly considered a criterion for
metabolic syndrome,
cardiac hypertrophy is often associated with
metabolic syndrome, and its presence carries increased cardiovascular risk. Recently it has been shown that
fructose and
fructokinase C (KHK) can be induced in cardiac tissue. Here we tested whether diet-induced
metabolic syndrome causes
heart disease associated with increased
fructose content and metabolism and whether it can be prevented with a
fructokinase inhibitor (
osthole). Male Wistar rats were provided a control diet (C) or high fat/
sugar diet for 30 days (MS), with half of the latter group receiving
osthol (MS+OT, 40 mg/kg/d). The Western diet increased
fructose,
uric acid, and
triglyceride concentrations in cardiac tissue associated with
cardiac hypertrophy, local
hypoxia, oxidative stress, and increased activity and expression of KHK in cardiac tissue.
Osthole reversed these effects. We conclude that the cardiac changes in
metabolic syndrome involve increased
fructose content and its metabolism and that blocking
fructokinase can provide cardiac benefit through the inhibition of KHK with modulation of
hypoxia, oxidative stress,
hypertrophy, and
fibrosis.