Pentamethylquercetin generates beneficial effects in monosodium glutamate-induced obese mice and C2C12 myotubes by activating AMP-activated protein kinase
Pentamethylquercetin generates beneficial effects in monosodium glutamate-induced obese mice and C2C12 myotubes by activating AMP-activated protein kinase
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DOI：
10.1007/s00125-012-2519-z
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发表时间：
2012-06-01
期刊：
影响因子：
8.2
通讯作者：
Jin, M. W.
中科院分区：
文献类型：
--
作者：
Shen, J. Z.;Ma, L. N.;Jin, M. W.
五甲基槲皮素 (PMQ) 最近被证明具有降血糖特性。在此，我们旨在表征 PMQ 在体内和体外改善代谢紊乱的有效性和潜在机制。我们通过新生儿给予谷氨酸钠 (MSG) 建立了肥胖小鼠模型，并用它来评估 PMQ 作为代谢紊乱治疗的特性。我们还研究了PMQ预防代谢紊乱的可能潜在机制。与正常小鼠相比，MSG小鼠存在代谢紊乱，包括中心性肥胖、高胰岛素血症、胰岛素抵抗、高血糖、高脂血症、AMP激活蛋白激酶（AMPK）和乙酰辅酶A羧化酶（ACC）磷酸化降低以及腓肠肌中GLUT4水平下调。在 MSG 小鼠中，PMQ 治疗（每天 5、10、20 mg/kg）可减少体重增加、腰围、脂肪组织量、血糖、三酰甘油和总胆固醇，同时改善胰岛素抵抗、激活 AMPK 并增加 ACC 磷酸化和 GLUT4 丰度。在 C2C12 肌管中，PMQ（10 μmol/l）使葡萄糖消耗增加约 65%。 PMQ 处理（1-10 mu mol/l）还激活 AMPK，增加 ACC 磷酸化和 GLUT4 丰度，并上调一些参与脂肪酸氧化的关键基因的表达。这些发现表明，PMQ 至少部分通过刺激 AMPK 活性来改善代谢紊乱。
Pentamethylquercetin (PMQ) has recently been shown to have glucose-lowering properties. Here, we aimed to characterise the effectiveness and underlying mechanisms of PMQ for ameliorating metabolic disorders in vivo and vitro.We generated a mouse model of obesity by neonatal administration of monosodium glutamate (MSG) and used it to assess the properties of PMQ as a treatment for metabolic disorders. We also investigated the possible underlying mechanisms of PMQ in the prevention of metabolic disorders.Compared with normal mice, MSG mice had metabolic disorders, including central obesity, hyperinsulinaemia, insulin resistance, hyperglycaemia, hyperlipidaemia, decreased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), and downregulated levels of GLUT4 in gastrocnemius muscles. In MSG mice, PMQ treatment (5, 10, 20 mg/kg daily) reduced body weight gain, waist circumference, adipose tissue mass, serum glucose, triacylglycerol and total cholesterol, while improving insulin resistance, activating AMPK and increasing ACC phosphorylation and GLUT4 abundance. In C2C12 myotubes, PMQ (10 mu mol/l) increased glucose consumption by similar to 65%. PMQ treatment (1-10 mu mol/l) also activated AMPK, increased ACC phosphorylation and GLUT4 abundance, and upregulated the expression of some key genes involved in fatty acid oxidation.These findings suggest that PMQ can ameliorate metabolic disorders at least in part via stimulation of AMPK activity.