左卡尼汀通过增加UCP1和p-AKT的表达活化高脂血症大鼠棕色脂肪细胞的研究

Activation of L-evocarnitine on brown adipocytes in hyperlipidemic rats by increasing the expression of UCP1 and p-AKT

目的探讨左卡尼汀对高脂喂养大鼠棕色脂肪的影响及其相关机制。方法将30只SD大鼠随机分为对照组、模型组和左卡尼汀低、中、高剂量(100、200、300mg/kg)组,每组各6只。每日ig给药,治疗12周后称重、处死大鼠,收集血清和棕色脂肪组织,检测血清相关生化指标,测定棕色脂肪组织中解偶联蛋白1(UCP1)和磷酸化AKT(p-AKT)的表达水平。结果与模型组相比,左卡尼汀100、200、300 mg/kg组的总胆固醇(TC)、三酰甘油(TG)明显降低,高密度脂蛋白胆固醇(HDL-C)明显升高(P<0.05);左卡尼汀100、200 mg/kg组的体质量明显降低,棕色脂肪组织(BAT)质量、BAT质量/体质量明显升高(P<0.05)。与模型组相比,左卡尼汀100、200mg/kg组BAT中UCP1RNA明显增加,差异有统计学意义(P<0.05)。与模型组相比,左卡尼汀组100、200、300mg/kg组BAT中UCP1和p-AKT蛋白表达明显增加,差异有统计学意义(P<0.05、0.01),且呈剂量相关性。结论左卡尼汀具有降脂和促进棕色脂肪活化的作用,这可能与其增加棕色脂肪组织中UCP1和p-AKT的表达有关。

Objective To investigate the effects of L-evocarnitine on brown adipose tissue in obese rats and its related mechanism. Methods Thirty SD rats were randomly divided into control group, model group, and L-evocarnitine(100, 200, and 300 mg/kg) groups. Each group had 6 cases, and ig administration with drugs per day. After 12 weeks of treatment, rats were sacrificed for collection of serum and brown adipose tissue. The expression levels of uncoupling protein 1(UCP1) and phosphorylated AKT(p-AKT) in brown adipose tissue were determined. Results Compared with the model group, TC and TG in L-evocarnitine 100, 200, and 300 mg/kg groups were significantly decreased(P < 0.05), but HDL-C in L-evocarnitine 100 and 200, 300 mg/kg groups was significantly increased(P < 0.05). Compared with the model group, the body weight in L-evocarnitine 100, 200 mg/kg groups were significantly decreased(P < 0.05), but BAT weight and BAT weight/body weight were significantly increased(P < 0.05). Compared with the model group, UCP1 RNA in L-evocarnitine 100 and 200 mg/kg groups was increased, with significant difference(P < 0.05). Compared with the model group, UCP1 and p-AKT protein in L-evocarnitine 100, 200, and 300 mg/kg groups were significantly increased(P < 0.05 and 0.01), with dose-dependent. Conclusion L-evocarnitine can reduce lipid and promote activation of brown adipose tissue, which may be related to its increasing expression of UCP1 and p-AKT in brown adipose tissue.