双去甲氧基姜黄素对肥胖模型小鼠糖脂代谢的影响及机制

Effects and Mechanism of Bisdemethoxycurcumin on Glucose and Lipid Metabolism in Obese Mice

关键词:  双去甲氧基姜黄素  肥胖  胰岛素抵抗  瞬时受体电位香草酸亚型1  腺苷酸活化蛋白激酶

Key words:  bisdemethoxycurcumin  obesity  insulin resistance  transient receptor potential vanilloid 1(TRPV1)  AMP-activated protein kinase (AMPK)

摘要:

目的 研究双去甲氧基姜黄素(bisdemethoxycurcumin,BDMC)对高糖高脂饮食诱导的肥胖小鼠胰岛素抵抗、糖脂代谢紊乱的影响,并探讨其机制。方法 C57BL/6小鼠40只随机分为正常组(10只)和高糖高脂饮食组(30只),正常组小鼠给予常规饲料,其余小鼠饲喂高糖高脂饮食诱导肥胖,造模8周。造模成功后,高糖高脂饮食组小鼠随机分为模型组、BDMC低剂量组(20 mg·kg^-1)、BDMC高剂量组(40 mg·kg^-1),每组10只。分别按剂量灌胃给药,每日1次,每周5次,连续8周。给药结束后,检测小鼠体质量、肝脏及脂肪重量,观察肝脏病理改变及脂质堆积情况,监测小鼠血糖、血脂、血清胰岛素等生化指标,并考察BDMC对TRPV1、AMPK及下游胰岛素信号、糖脂代谢通路的影响。结果 与正常组相比,模型组小鼠体质量及脏器指数增加,肝脏出现明显的病理改变,脂质堆积严重,血清胰岛素、血糖、血脂参数(TC、TG、LDL-C)显著增高,HDL-C显著降低;肝损伤(ALT、AST)加重;肝脏组织中TRPV1、SREBP、FAS蛋白表达显著升高,p-IRS1、p-AMPK、GLUT4、p-ACC表达显著降低。与模型组相比,给予BDMC治疗后,肝脏脂质堆积减少,组织病理改变得到改善,血糖、血清胰岛素、TC、TG、LDL-C、ALT、AST显著降低(P<0.05),HDL-C显著升高,肝脏中p-IRS1、p-AMPK、GLUT4、p-ACC表达升高,TRPV1、SREBP、FAS表达显著降低(P<0.05)。结论 BDMC能改善胰岛素抵抗,调节糖脂代谢紊乱,治疗高糖高脂饮食诱导的肥胖,其作用可能与调节TRPV1和AMPK信号通路有关。

Abstract:

OBJECTIVE To study the effects of bisdemethoxycurcumin(BDMC) on insulin resistance and disorders of glucose and lipid metabolism in high glucose/high fat diet-induced obese mice, and to explore its mechanism. METHODS Forty C57BL/6 mice were randomly divided into the normal group(10 mice) and the high-sugar and high-fat diet group(30 mice). The mice in the normal group were given conventional feed, and the other mice were fed high-sugar and high-fat diet to induce obesity for 8 weeks. After successful modeling, mice in the high-sugar and high-fat diet group were randomly divided into model group, BDMC low-dose group(20 mg·kg^-1), and BDMC high-dose group(40 mg·kg^-1), with 10 mice in each group. They were administered by gavage once a day, 5 times a week for 8 consecutive weeks. At the end of experiment, body weight, liver and adipose weight, the pathological changes and lipid accumulation in the liver of mice, biochemical indexes including blood glucose, blood lipid, serum insulin and others were monitored. The effects of BDMC on TRPV1, AMPK, the downstream insulin signal and glucose and lipid metabolism pathway were investigated. RESULTS Compared with the normal group, the body weight and organ index of mice in the model group were increased, the liver showed obvious pathological changes, the lipid accumulation was serious, the serum insulin, blood glucose and blood lipid parameters(TC, TG, LDL-C) were significantly increased, and HDL-C was significantly decreased; liver injury(ALT, AST) aggravated; the expression of TRPV1, SREBP and FAS in liver tissue was significantly increased, and the expression of p-IRS1, p-AMPK, GLUT4 and p-ACC was significantly decreased. Compared with the model group, after treatment with BDMC, liver lipid accumulation was reduced, histopathological changes were restored, blood glucose, serum insulin, TC, TG, LDL-C, ALT, AST were significantly decreased(P<0.05), HDL-C was significantly increased, p-IRS1, p-AMPK, GLUT4, p-ACC expression in liver was increased, TRPV1, SREBP, FAS expression was significantly decreased(P<0.05). CONCLUSION BDMC can improve insulin resistance and regulate metabolism disorders of glucose and lipid to treat high-sugar and high-fat diet induced obesity, and which may be related to the regulation of TRPV1 and AMPK.