辅酶Q10对高脂膳食小鼠的胆汁酸代谢和肥胖及相关脂质代谢紊乱的影响

Effects of coenzyme Q10 on bile acid metabolism,obesity,and related lipid metabolism disorders in high-fat diet mice

目的探索辅酶Q10(coenzyme Q10,CoQ10)对高脂膳食诱导的小鼠肥胖、脂质紊乱及胆汁酸代谢的影响。方法8周龄C57BL/6J小鼠根据体重按照随机区组法随机分为对照组(普通饲料)、高脂膳食组(45%高脂饲料)和CoQ10干预组(45%高脂饲料+100 mg·kg^(-1)·d^(-1) CoQ10)。收集各组小鼠体重、摄食量数据;试剂盒检测血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、丙氨酸转氨酶和天冬氨酸转氨酶水平;超高效液相色谱串联质谱(UPLC-MS/MS)检测小鼠血清、肝脏和结肠中17种胆汁酸的含量,Western印迹检测肝脏中胆固醇12α-羟化酶(cholesterol 12α-hydroxylase,CYP8B1)和氧固醇7α-羟化酶(oxysterol 7α-hydroxylase,CYP7B1)蛋白的表达。结果CoQ10显著降低了高脂膳食小鼠的体重并改善其脂质代谢紊乱。与对照组相比,高脂膳食组小鼠血清总胆汁酸水平降低(P<0.05);与高脂膳食组相比,CoQ10干预升高了小鼠血清和结肠中的总胆汁酸水平(P=0.021,P=0.014),并提高了小鼠肝脏、结肠和血清中脱氧胆酸和熊脱氧胆酸的水平(P<0.05)。CoQ10干预组小鼠结肠和血清脱氧胆酸水平均与小鼠体重呈负相关(P=0.024,P=0.019),结肠脱氧胆酸和总胆固醇水平也呈负相关(P=0.006)。CoQ10上调了高脂膳食小鼠肝脏中CYP8B1和CYP7B1蛋白的表达。结论CoQ10能够调节高脂膳食小鼠的胆汁酸代谢并减轻其肥胖及脂质代谢紊乱。

Objective To explore the effects of coenzyme Q10(CoQ10)on high-fat diet-induced obesity,lipid disorders,and bile acid metabolism in mice.Methods Eight-week-old C57BL/6J mice were randomly divided into control group(regular chow),high-fat diet group(45%high-fat chow),and CoQ10 intervention group(45%high-fat chow+100 mg·kg^(-1)·d^(-1)CoQ10)based on their body weights according to the randomized block design.The body weight and food intake of mice in each group were collected.The levels of serum total cholesterol,triglyceride,low density lipoprotein-cholesterol,high density lipoprotein-cholesterol,alanine aminotransferase,and aspartate aminotransferase were detected.The contents of 17 bile acids in serum,liver,and colon contents of mice were detected by ultra-performance liquid chromatography-tandem mass(UPLC-MS/MS).The protein expressions of cholesterol 12α-hydroxylase(CYP8B1)and oxysterol 7α-hydroxylase(CYP7B1)in liver were detected by Western blotting.Results CoQ10 significantly reduced body weight and ameliorated lipid metabolism disorders in mice fed a high-fat diet.Compared with the control group,serum total bile acid levels were reduced in the high-fat diet group(P<0.05);CoQ10 intervention elevated serum and colonic total bile acid levels(P=0.021,P=0.014)and increased liver,colon,and serum deoxycholic acid and ursodeoxycholic acid levels(P<0.05)in the mice compared with the high-fat diet group.Both colonic and serum deoxycholic acid levels in the CoQ10 intervention group were negatively correlated with body weights(P=0.024,P=0.019),and colonic deoxycholic acid and total cholesterol levels were also negatively correlated(P=0.006).CoQ10 increased the expression of CYP8B1 and CYP7B1 proteins in the liver of mice.Conclusion CoQ10 can modulate bile acid metabolism in high-fat diet-fed mice and alleviate their obesity and lipid metabolism disorders.