Objective: To investigate the effect of yacon root extract on lipid metabolism in rats with hyperlipidemia (HLP) and its underlying mechanisms.
Methods: SD rat models of HLP induced by high- fat diet feeding for 8 weeks were randomized into the model group, fenofibrate treatment group (27 mg/kg), and yacon extract treatment groups at doses of 5, 2.5 and 1.25 g/kg (n=10). The rats were given corresponding drug treatments via gavage for 8 weeks. After the treatments, the rats were observed for body weight changes, liver coefficient, liver pathology, and serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The mRNA and protein expressions of HMGCR, PPARα, CYP7A1, and CPT-1 in the liver were detected using RT-qPCR and Western blotting.
Results: Compared with those in the model group, the rats treated with fenofibrate and 5 g/kg yacon root extract showed significantly slower body weight gain and lower liver coefficient (P < 0.05) with lower serum levels of TG, TC, and LDL- C (P < 0.05) but higher HDL- C level (P < 0.05). The HLP rat models showed obvious fatty degeneration and vacuolar changes in the liver, which were significantly alleviated by fenofibrate treatment and by treatment with yacon root extract in a dose-dependent manner. Both fenofibrate and 5 g/kg yacon root extract significantly lowered the mRNA and protein expression levels of HMGCR (P < 0.001) and increased the expressions of PPARα, CYP7A1, and CPT-1 in the liver of HLP rats (P < 0.001).
Conclusion: Yacon root extract can reduce serum TG and TC levels in HLP rats possibly by inhibiting HMGCR expression and activating the PPARα/CYP7A1/CPT-1 signaling pathway, thereby promoting fatty acid β oxidation and bile acid metabolism.
目的: 探究雪莲果（Yacon）浸膏对高脂血症（HLP）大鼠脂质代谢的影响和改善血脂异常的作用机制。
方法: 随机数表法取10只SD大鼠作为空白组（Normal），正常饮食；另取50只大鼠给予高脂饮食8周建立HLP模型，随机分为模型组（Mod）、非诺贝特阳性对照组（FEN，27 mg/kg），Yacon浸膏高、中、低剂量组（5、2.5、1.25 g/kg），10只/组。各组大鼠给予相应药物灌胃，Normal组、Mod组给予等体积生理盐水，干预8周。观察并记录大鼠体质量变化，采集肝脏、血清标本，计算肝脏系数；ELISA法检测血清中甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平；HE染色法观察肝组织病理变化；qPCR和Western blot法分别检测3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）、过氧化物酶增殖物激活受体α（PPARα）、胆固醇7α-羟化酶（CYP7A1）、肉碱棕榈酰转移酶1（CPT-1）mRNA及蛋白表达水平。
结果: FEN组和Yacon 5 g/kg组体质量增量、肝脏系数均低于Mod组（P < 0.05）；FEN组和Yacon 5 g/kg组血清TG、TC、LDL-C水平均低于Mod组（P < 0.05），HDL-C水平高于Mod组（P < 0.05）；光镜下观察大鼠肝脏病理组织切片，Mod组可见脂肪样变性和空泡样改变等病理变化，药物各治疗组病理程度明显减轻且具有剂量依赖性；与Mod组相比，FEN组和Yacon 5 g/kg组大鼠肝组织中HMGCR mRNA及蛋白表达水平降低（P < 0.001），PPARα、CYP7A1、CPT-1 mRNA及蛋白表达水平升高（P < 0.001）。
结论: Yacon浸膏可以降低HLP大鼠血清TG、TC水平，其机制可能与抑制肝脏HMGCR的表达和激活PPARα/CYP7A1/CPT-1信号通路，促进脂肪酸β氧化、胆汁酸代谢有关。
Keywords: HMGCR; PPARα; hyperlipidemia; lipid metabolism; yacon root extract.