Abstract
BACKGROUND: Both ACE inhibitors and allopurinol have been shown to partially prevent metabolic syndrome induced by fructose. We tested the hypothesis that combined therapy might be more effective at blocking the metabolic syndrome induced with fructose. METHODS: Male Sprague-Dawley rats were fed a high fructose diet with or without allopurinol, captopril, or the combination for 20 weeks. A control group received a normal diet. All groups were pair-fed to assure equivalent caloric intake. RESULTS: Despite reduced energy intake, the fructose-fed rats developed features of metabolic syndrome including elevated blood pressure, abdominal obesity, hypertriglyceridemia, hyperuricemia and hyperinsulinemia. While both allopurinol and captopril alone tended to reduce features of the metabolic syndrome, the combined therapy was synergistic, with significant reduction in blood pressure, less accumulation of abdominal fat, an improvement in the dyslipidemia and a complete prevention of insulin resistance. CONCLUSION: A high fructose diet can induce metabolic syndrome even in the setting of caloric restriction. Captopril and allopurinol synergistically reduce features of the metabolic syndrome, especially hypertension, insulin resistance and dyslipidemia. Combination allopurinol and ACE inhibitor therapy might provide a superior means to prevent diabetes and cardiovascular disease.