奥利司他对营养性肥胖小鼠糖脂代谢及代谢相关脂肪性肝病的影响

Effects of orlistat on glucose and lipid metabolism and metabolically associated fatty liver disease in nutritionally obese mice

目的明确奥利司他在减重之外对代谢相关脂肪性肝病(metabolically associated fatty liver disease,MAFLD)的影响,观察奥利司他对营养性肥胖小鼠体重、血糖、血脂及肝脏脂肪细胞的影响。方法雄性C576LBJ小鼠30只,正常对照组(NC)(n=10)给予普通饲料+蒸馏水(与NODTG组同体积)灌胃9周;营养性肥胖实验对照组(NOTG)(n=10)给予60%高脂饲料+0.5%CMC(与NODTG组同体积)灌胃9周;营养性肥胖奥利司他治疗组(NODTG)(n=10)给予60%高脂饲料+奥利司他灌胃9周;剂量为60 mg/(kg·d),每次30 mg/kg,每12 h灌胃。每周测小鼠体重及每周增重(△m),第0周及第9周测空腹血糖(FPG),第9周测血清总胆固醇(TC)、甘油三酯(TG),并进行肝活检,组织切片油红O染色,200倍显微镜视野下对肝脏脂肪细胞定性、定量观察并拍照记录。结果第9周NC组、NOTG组、NODTG组每周平均增重分别为(0.2077±0.3397)g、(0.7777±0.3011)g、(0.4838±0.2795)g。与NC组相比,进食高脂饮食增重明显(P<0.01)。与单纯进食高脂饮食的NOTG组比较,连续应用9周奥利司他治疗,每周增重显著下降(P<0.01),奥利司他组在进食高脂饮食时可获得更好的体重管理。第9周NC组、NOTG组、NODTG组FPG分别为(6.00±0.55)mmol/L、(10.62±2.95)mmol/L、(7.41±2.59)mmol/L。NOTG组较NC组FPG明显升高(P<0.01),奥利司他治疗后FPG显著下降(P=0.0002)。第9周总胆固醇水平分别为(1.70±0.39)mmol/L、(4.18±0.82)mmol/L、(2.53±0.48)mmol/L,NOTG组较NC组明显升高(P<0.001),NODTG组较NOTG组明显下降(P<0.001)。第9周甘油三酯水平分别为(1.12±0.14)mmol/L、(1.53±0.16)mmol/L、(1.30±0.14)mmol/L。NOTG组较NC组明显升高(P<0.05),NODTG组较NOTG组显著下降(P<0.05),差异均有统计学意义。200倍显微镜下观察肝脏脂肪细胞,NOTG组较NC组油红O染色面积增加(P<0.05),NODTG组较NOTG组油红O染色面积减少(P<0.05)。结论奥利司他可在减轻体重的同时改善血糖、血脂,减少肝细胞脂肪沉积,降低心血管危险因素。

Objective To determine the effect of orlistat on metabolically associated fatty liver disease(MAFLD)in addition to weight loss,and the effects of orlistat on weight,blood glucose,and lipid,and liver fat cells in nutritionally obese mice.Methods Thirty male C576 LBJ mice,normal control group(NC)(n=10)for ordinary feed and distilled water(same volume with NODTG group)lavage 9 weeks,nutritional obese control group(NOTG)(n=10)60%for high fat forage and 0.5%CMC(same volume with NODTG group)lavage 9 weeks,nutritional obesity orlistat treatment group(NODTG)(n=10)60%for high fat forage and 9 weeks of orlistat lavage dose for 60 mg/(kg·d),Each time 30 mg/kg,Q12 h.Weight and weight gain(△m)of mice were measured weekly.Fasting blood glucose(FPG)was measured at week 0 and 9,and serum total cholesterol(TC)and triglyceride(TG)were measured at week 9.Meanwhile,liver biopsy was performed at the 9 th week.The tissue sections were stained with oil red O staining and liver fat cells were observed qualitatively and quantitatively under a 200-fold microscope field and photographed.Results On 9 th week,the average weight gain in NC group,NOTG group and NODTG group were(0.2077±0.3397)g,(0.7777±0.3011)g and(0.4838±0.2795)g,respectively.Compared with NC group,eating high-fat diet increased the weight significantly(P<0.01).Compared with the NOTG group on a high-fat diet alone,there was a significant decrease in weight gain per week after 9 weeks of orlistat treatment(P<0.01),and the orlistat group achieved better weight management on a high-fat diet.At week 9,FPG in NC group,NOTG group and NODTG group were(6.00±0.55)mmol/L,(10.62±2.95)mmol/L and(7.41±2.59)mmol/L,respectively.FPG was significantly higher in the NOTG group than in the NC group(P<0.01),and significantly decreased after orlistat treatment(P=0.0002).At the 9 th week,the total cholesterol level were(1.70±0.39)mmol/L,(4.18±0.82)mmol/L,and(2.53±0.48)mmol/L,respectively.The NOTG group was significantly higher than the NC group(P<0.001),and the NODTG group was significantly lower than the NOTG group(P<0.001).At week 9,the triglyceride levels were(1.12±0.14)mmol/L,(1.53±0.16)mmol/L,and(1.30±0.14)mmol/L,respectively.The NOTG group was significantly higher than the NC group(P<0.05),and the NODTG group was significantly lower than the NOTG group(P<0.05).The difference was statistically significant.Liver fat cells were found under a 200-fold microscope field,the staining area of oil red O in the NOTG group increased compared with the NC group(P<0.05),while that in the NODTG group decreased(P<0.05).Conclusion Orlistat may improve hepatocyte fat deposition,blood glucose and lipidand,and further reduce cardiovascular risk factors accompany with reducing body weight.