蛋氨酸限制和胶原蛋白肽对高脂饮食小鼠脂代谢和氧化应激的联合作用

目的：研究饮食蛋氨酸限制（methionine restriction，MR）和胶原蛋白肽对高脂饮食小鼠肝脏脂代谢和氧 化应激的联合作用。方法：将36 只C57BL/6雄性小鼠随机分为4 组：低脂正常饮食组（ND组）、高脂饮食组（HF 组）、高脂蛋氨酸限制组（MR组）及高脂蛋氨酸限制和胶原蛋白肽联合作用组（PMR组）。每周监测体质量，22 周实验结束，测定血浆中的甘油三酯（triglyceride，TG）、总胆固醇（total cholesterol，TC）、高密度脂蛋白胆固 醇、低密度脂蛋白胆固醇和游离脂肪酸（free fatty acid，FFA）含量；测定肝脏中的TG和TC含量；测定肝脏和血浆 中的总抗氧化能力（total antioxidant capacity，T-AOC）、谷胱甘肽过氧化物酶（glutathion peroxidase，GSH-Px） 活力和丙二醛（malondialdehyde，MDA）含量；实时荧光定量聚合酶链式反应（quantitative real time polymerase chain reaction，qPCR）测定脂代谢相关基因固醇调节元件结合蛋白1c（sterol regulatory element-binding protein 1c，SREBP1c）、脂肪酸合成酶（fatty acid synthase，FAS）、乙酰辅酶A羧化酶（acetyl CoA-carboxylase 1， ACC-1）、胆固醇7α-羟化酶（cholesterol 7α-hydroxylase，CYP7A1）、对肉碱酰基转移酶1（carnitine palmityl transferase 1，CPT1）和过氧化物酶体增殖物激活受体α（peroxisome proliferator activated receptor α，PPARα）的表 达。结果：与HF组相比，MR组小鼠体质量、肝脏中的TG和TC含量极显著降低（P＜0.01）；肝脏脂肪合成相关基 因FAS和SREBP1c极显著下调（P＜0.01），ACC-1显著下调（P＜0.05）；脂肪分解相关基因CYP7A1和PPARα极显 著上调（P＜0.01），CPT1显著上调（P＜0.05）；肝脏中T-AOC和GSH-Px活力显著增加（P＜0.05），MDA和活 性氧含量极显著降低（P＜0.01）；血浆中T-AOC和GSH-Px活力极显著增加（P＜0.01），血浆MDA和全血活性氧 含量极显著降低（P＜0.01）。与MR组相比，PMR组体质量和肝脏中的TG含量极显著降低（P＜0.01）；血浆中的 TG和TC含量显著降低（P＜0.05）；脂肪合成相关基因SREBP1c和ACC-1显著下调（P＜0.05）；脂肪分解相关基因 CPT1和PPARα显著上调（P＜0.05）；肝脏GSH-Px活力显著增加（P＜0.05）。结论：蛋氨酸限制饮食能显著降低 高脂饮食小鼠血脂和肝脏脂肪积累，增强肝脏抗氧化能力，且蛋氨酸限制与胶原蛋白肽的联合作用更能显著降低高 脂饮食小鼠血脂和肝脏脂肪积累，增强肝脏抗氧化能力。

Combined Effect of Methionine Restriction and Collagen Peptides on Lipid Metabolism and Oxidative Stress in High-Fat Diet-Fed Mice

Purpose: To ascertain the combined effect of methionine restriction (MR) and collagen peptides on lipid metabolism and oxidative stress in high-fat-diet (HFD)-fed mice. Methods: Thirty-six male C57BL/6 mice were randomly and evenly divided into normal diet (ND), high-fat diet (HFD), high-fat with MR diet (MR), and MR diet supplemented with 1% collagen peptides (PMR) groups, respectively. Body weight was measured weekly. At the end of the 22-week feeding period, all mice were sacrificed. Plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and free fatty acids (FFAs) were examined. The concentrations of TG and TC in liver were investigated. The levels of total antioxidant capacity (T-AOC), glutathion peroxidase (GSH-Px), and malondialdehyde (MDA) in liver and plasma were determined. The mRNA expression of fatty acid synthase (FAS), acetyl CoA-carboxylase 1 (ACC-1), sterol regulatory element-binding protein 1c (SREBP1c), cholesterol 7α-hydroxylase 1 (CYP7A1), carnitine palmityl transferase 1 (CPT1) and peroxisome proliferator activated receptor α (PPARα) in liver were assayed by quantitative real time polymerase chain reaction (qPCR). Results: Compared with the HFD group, MR significantly decreased body weight, TG and TC concentrations in liver (P < 0.01), MDA levels in plasma and liver and reactive oxygen species levels in blood and liver (P < 0.01), and down-regulated the expression of FAS (P < 0.01), SREBP1c (P < 0.01) and ACC-1 (P < 0.05) in liver. MR significantly increased GSH-Px and T-AOC activity in liver (P < 0.05) and plasma (P < 0.01), and up-regulated the expression of CYP7A1 (P < 0.01), PPARα (P < 0.01) and CPT1 (P < 0.05) in liver. Compared with the MR group, PMR significantly decreased body weight and TG concentration in liver (P < 0.01) as well as TG and TC concentrations in plasma (P < 0.05), down-regulated the expression of SREBP1c and ACC-1 in liver (P < 0.05), up-regulated the expression of PPARα and CPT1 (P < 0.05), and increased GSH-Px activity in liver (P < 0.05). Conclusion: Dietary methionine restriction can significantly decrease blood and liver lipid accumulation, enhance liver antioxidant capacity in HFD-fed mice and has a synergistic effect when combined with collagen peptides.