共轭亚油酸改善肥胖糖尿病小鼠的糖脂代谢

目的分析共轭亚油酸（CLA）对肥胖糖尿病（db/db）小鼠糖脂代谢的改善效果。方法将db/db 小鼠分为生理盐水组和CLA实验组分别给予生理盐水，CLA混合物灌胃处理，测量小鼠体质量、饮食摄入量、饮水量、口服糖耐量、甘油三酯、总胆固醇水平。HE染色和油红“O”染色检测肝脏病理学改变和脂肪酸含量。荧光定量PCR和Western blot 实验检测PPARα、PPARγ、CD36、CHREBP和SREBP-1c 等基因表达水平。分别用共轭亚油酸和亚油酸处理HepG2 细胞，检测PPARα、ACC、P-ACC、CD36等基因的表达。同时检测细胞上清中乙酰辅酶A的含量。结果共轭亚油酸能减少db/db小鼠饮食、饮水量，有效减轻小鼠体重，降低血清甘油三酯和胆固醇水平（P<0.05）。共轭亚油酸能降低db/db小鼠空腹血糖，提高糖耐量。肝脏病理学切片和油红“O”染色结果表明共轭亚油酸能减少肝脏里脂滴累积，有效改善脂代谢。共轭亚油酸能上调肝脏组织PPARα表达（P<0.05），下调CD36表达（P<0.001）。细胞实验显示共轭亚油酸能上调PPARα（P<0.001），上调P-ACC，同时下调CD36（P<0.01）表达；ELISA结果显示CLA处理后细胞中乙酰辅酶A显著上调（P<0.01）。结论两种共轭亚油酸同分异构体混合物能够明显改善db/db小鼠糖脂代谢，降低空腹血糖，提高糖耐量，对肥胖、糖尿病动物模型产生综合性的治疗效果。其作用机制可能是通过上调转录因子PPARα，下调脂质转运蛋白CD36，促进ACC磷酸化来调控糖脂代谢。

Conjugated linoleic acid improves glucose and lipid metabolism in diabetic mice

Objective To analyze the effect of conjugated linoleic acid (CLA) on glucose and lipid metabolism in obese diabetic(db/db) mice. Methods db/db mice were randomized for treatment with saline or CLA mixture administered intragastrically.The changes in body weight, dietary intake, water intake, oral glucose tolerance, triglyceride and total cholesterol wererecorded after the treatments. HE staining and oil red O staining were used to assess liver pathologies and fatty acid content.The expression levels of PPARα, PPARγ, CD36, CHREBP and SREBP-1c were detected using real-time PCR and Westernblotting. HepG2 cells were treated with CLA and linoleic acid and the expressions of PPARα, ACC, P-ACC, and CD36 weredetected; the level of acetyl-CoA in the cell supernatant was detected using ELISA. Results CLA treatment obviously reducedthe dietary and water intake of db/db mice, effectively reduced the body weight and decreased serum triglyceride andcholesterol levels (P<0.05). CLA significantly reduced fasting blood glucose, increased glucose tolerance, reduced theaccumulation of lipid droplets in the liver and improved lipid metabolism in db/db mice. The mice showed significantlyincreased expression of PPARα (P<0.05) and lowered CD36 expression (P<0.001) in the liver after CLA treatment. Cellularexperiments showed that CLA significantly up-regulated PPARα (P<0.001) and P-ACC and decreased the expression of CD36(P<0.01). ELISA showed that acetyl-CoA was significantly up-regulated in the cells after CLA treatment (P<0.01). ConclusionThe mixture of two conjugated linoleic acid isomers can reduce fasting blood glucose, increase glucose tolerance and improveglycolipid metabolism in db/db mice by enhancing the expression of PPARα, increasing P-ACC and inhibiting CD36expression.