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| Fructose excess consumption induces insulin resistance-associated metabolic diseases. Hypothalamic insulin signaling plays a pivotal role in controlling whole-body insulin sensitivity and energy homeostasis. Wuling San and its modifications exerted various effects including anti-hypertension, anti-inflammation, anti-dyslipidemia and anti-insulin resistance. In this study, we investigated its regulatory effects on the hypothalamus of high fructose-fed mice. Mice were fed 30% fructose in drinking water for 12 weeks. After 6 weeks, these animals were orally treated with Wuling San (987, 1316, 1755 and 2340 mg/kg), allopurinol (5 mg/kg) and water daily for the next 6 weeks, respectively. Wuling San ameliorated fructose-induced hypertension, hyperlipidemia, and hyperinsulinemia and insulin resistance in mice. Wuling San ameliorated high fructose-caused hypothalamic inflammation in mice by suppressing the activation of hypothalamic nuclear factor κB (NF-κB) pathway and NOD-like receptor 3 (NLRP3) inflammasome. Wuling San also effectively restored high fructose-induced hypothalamic insulin signaling defect by up-regulating the phosphorylation of insulin receptor and protein kinase B. Allopurinol had similar effects. These results provide in vivo evidence that Wuling San-mediated inhibition of NF-κB pathway/NLRP3 inflammasome activation in the hypothalamus of mice may be associated with the reduction of hypothalamic inflammatory lesions, contributing to the improvement of hypothalamic insulin signaling defect in this model. Thus, Wuling San with the central activity may be a therapeutic for high fructose-induced metabolic syndrome in humans. |
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| Keywords:Wuling San; hypothalamic inflammation; hypothalamic insulin signaling defect |
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