Abstract
To investigate the dysfunction of leptin underlying insulin resistance syndrome in fructose-fed rats and improvement by lowing uric acid with natural products quercetin and rutin. Rats were fed with fructose solution for 8 weeks. At week 4, animals received quercetin and rutin, as well as allopurinol. Serum uric acid and insulin levels were measured before and after drug treatment. Leptin levels in serum and hypothalamus, leptin secretion from adipose tissue were used to evaluate the responses of leptin to hyperuricemia and hyperinsulinemia in rats with insulin resistance syndrome. Triglyceride (TG), high dense lipid (HDL) and low dense lipid (LDL) in serum were examined to evaluate dyslipidemia in fructose-fed rats. Fructose consumption significantly increased serum uric acid, insulin and leptin levels in rats, and induced a significant increase of leptin secretion by upregulating ob gene expression in adipose tissue. Quercetin and rutin, as well as allopurinol reduced hyperleptinemia and inhibited leptin secretion from adipose tissue. Moreover, fructose-fed rats exhibited leptin level increase in hypothalamus accompanying dyslipidemia. Quercetin, rutin and allopurinol attenuated fructose-induced dyslipidemia in rats, but failed to improve leptin insufficiency in hypothalamus. These results indicated that fructose consumption might cause hyperleptinemia and leptin insufficiency in the brain, which might be indirectly mediated by hyperinsulinemia and hypertriglyceridemia in rats. Hopouricemic agents quercetin, rutin and allopurinol improved hyperinsulinemia and dyslipidemia, and subsequently regulated leptin dysfunction in fructose-fed rats. This study provided direct evidence that hyperuricemia was associated with hyperleptinemia during fructose consumption, and another pharmacological explanation for lowing uric acid agents to prevent hyperuricemia and leptin dysfunctions in fructose-induced insulin resistance syndrome in rats.
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