高脂饮食对老年大鼠肝脏脂肪酸代谢及胰岛素敏感性的影响

Effects of high-fat diet on fatty acid metabolism in liver and insulin sensitivity in aged rats

目的探讨增龄和高脂饮食对大鼠肝脏脂肪酸代谢及胰岛素敏感性的影响，了解老年大鼠胰岛素抵抗（IR）的发病机制。方法将22～24月龄雄性Wistar大鼠随机分为老年对照组和高脂组；4～5月龄大鼠作为青年对照组。老年对照组和青年对照组给予基础饲料，高脂组给予高脂饲料，喂养8周。用高胰岛素-正葡萄糖钳夹实验评价各组大鼠胰岛素敏感性；肝脏三酰甘油经氯仿／甲醇抽提后用全自动生化分析仪测定。结果（1）老年对照组空腹血糖、胰岛素和游离脂肪酸均高于青年对照组，高脂组进一步升高，且血清三酰甘油和总胆固醇水平增高；（2）葡萄糖输注率老年对照组[（23．80±2．79）mU·kg^-1·min^-1]较青年对照组[（30．08±3．89）mU·kg^-1·min^-1]低，高脂组[（18．83±2．18）mU·kg^-1·min^-1]最低，差异有统计学意义（P〈0．01）；高脂组8周末较4周末低；（3）肝脏三酰甘油老年对照组较青年对照组升高，分别为（16．6±4．8）μmol／g和（9．6士2．2）μmol／g，高脂组（24．7±6．6）μmol／g较老年对照组进一步升高（P〈0．01）；在老年组中，肝脏三酰甘油与葡萄糖输注率呈负相关，与空腹血糖呈正相关。结论与青年对照组比较，老年对照组更易出现脂肪酸代谢异常及IR；高脂饮食导致老年大鼠肝脏脂质积聚更加严重，进一步加重IR；肝脏脂质堆积可能参与了与增龄和高脂饮食相关IR的发生。

Objective To investigate the effects of high-fat diet on fatty acid metabolism in liver and insulin sensitivity in aged rats and to explore the mechanisms of insulin resistance associated with aging. Methods Male Wistar rats aged 22-24 months were randomly divided into old control （OC） group and high fat diet （HF） group. Male Wistar rats aged 4-5 months were selected as young control （YC） group. The rats in OC and YC were fed with basic diet, and the rats in HF group received high fat diet. Insulin sensitivity was evaluated by hyperinsulinemic-euglyeemic clamp technique. Extracted liver triglyceride was measured by an automated biochemistry analyzer. Results （1） Compared with YC group, fasting blood glucose（FBG）, fasting insulin（FINS） and free fatty acid were increased in OC group and were increased significantly in HF group. Triglyceride（TG） and total cholesterol（TC） levels were also elevated in HF group. （2） Compared with YC group, glucose infusion rate （GIR） was reduced in OC group and was decreased significantly in HF group. GIR was lower at the end of the 8th week than that at the end of the 4th week in HF group. （3） Compared with YC group, liver triglyceride was increased in OC group and was increased significantly in HF group. Liver triglyceride was negatively correlated with GIR, and positively correlated with FBG. Conclusions Compared with young rats, abnormal fatty acid metabolism and insulin resistance always exist in aged rats. High-fat feeding results in a significant increase in lipid content in liver and more serious insulin resistance in aged rats. Lipid accumulation in liver may contribute to insulin resistance associated with aging and high-fat diet.