白藜芦醇改善饮食诱导肥胖斑马鱼脂代谢的研究

摘要

目的：研究白藜芦醇（RSV）对饮食诱导肥胖斑马鱼脂代谢的影响。方法：120条野生型成年雄性斑马鱼（AB系），随机分为4组，即正常喂饲组（Con），正常喂饲+RSV组（Con+RSV），过度喂饲组（DIO），过度喂饲+RSV组（DIO+RSV）。每条鱼正常喂饲虫卵量每天为8 mg，过量喂饲量为每天60 mg，RSV干预剂量为20μmol/L，每天11 h。实验持续8周。实验结束时测定鱼体长、体质量，计算肥满度，检测血浆甘油三酯（TG）和总胆固醇（TC），观察肝组织形态。检测鱼体pAMPKα/AMPKα、Sirt1、Cav-1和LC3蛋白表达水平。结果：DIO组斑马鱼体长、体质量和肥满度较对照组分别增加11.7%、61.9%和15.1%（P＜0.01），虽然喂食量和RSV对斑马鱼体长的影响存在交互效应（P＜0.05），但RSV干预对上述指标的影响差异均无统计学意义（P＞0.05）。RSV干预能显著改善过度喂饲诱导的脂肪浸润和肝脏脂滴形成，上调鱼体AMPKα蛋白磷酸化水平及显著提升Sirt1蛋白表达水平（725.8% DIO+RSV组 vs DIO组，P＜0.01），RSV干预同时显著提升自噬标志蛋白LC3-II的水平（P＜0.05）。结论：RSV在没有影响体长、体质量和血脂的情况下，可以调节饮食诱导肥胖斑马鱼的脂代谢，这可能与pAMPKa/Sirt1/自噬通路有关。%Objective:To investigate the effect of resveratrol (RSV) on lipid metabolism in diet-induced obese zebrafish. Methods: One hundred and twenty adult zebrafish (Danio rerio) of the wild-type strain (AB) were randomly allocated into 4 groups: control group (Con), Con+RSV, diet-induced obese (DIO), and DIO+RSV. The Con group was fed on freshly hatched live Artemia (8 mg cysts/ifsh/day) once a day for 8 weeks. The DIO group was fed on freshly hatched live Artemia (60 mg cysts/ifsh/day) three times a day for 8 weeks. The ifsh were exposed to 20 mmol/L resveratrol for 11 hours every day. After 8 weeks, the body length, body weight, total cholesterol (TC), and triglyceride (TG) were measured. The histology of the liver was evaluated. The protein levels of pAMPKα, AMPKα, Sirt1, caveolin-1 (Cav-1) and LC3-II were analyzed by western blot-ting. Results:After 8 weeks, the body length, body weight and condition factor increased by 11.7%, 61.9%and 15.1%(P<0.01), respectively. There was interaction effect on body length between the food intake and resvera-trol (P=0.033), but resveratrol had no effect on the above parameters. Resveratrol could signiifcantly alleviate the fatty inifltration and the formation of lipid droplets in the liver, and resveratrol up-regulated protein levels of pAMPKα, Sirt1 (725.8% DIO+RSV group vs. DIO group, P<0.01) and autophagy marker protein LC3-II (P=0.047). Conclusion:Without affecting the body length, body weight and lipid parameters, resveratrol amelio-rates the lipid metabolism via pAMPK/Sirt1/autophagy pathway in the diet-induced obese zebraifsh.