二氢杨梅素经激活SIRT1-AMPK通路抑制高脂饮食诱导的肥胖小鼠肝脏脂质沉积

目的探究二氢杨梅素(dihydromyricetin,DHM)对高脂饮食诱导的肥胖小鼠肝脏脂质蓄积的作用及其机制。方法C57BL/6J小鼠60只,随机分为6组(n=10):①ND组:正常饲料;②ND+L-DHM组:正常饲料+低剂量DHM(125 mg·kg^-1·d^-1);③ND+H-DHM组:正常饲料+高剂量DHM(250 mg·kg^-1·d^-1);④HFD组:高脂饲料;⑤HFD+L-DHM组:高脂饲料+低剂量DHM;⑥HFD+H-DHM组:高脂饲料+高剂量DHM。记录小鼠体重;16周后,测空腹血脂;计算体脂重量;肝脏HE和油红O染色;荧光定量PCR和Western blot检测肝脏SIRT1、AMPK、ACC、FAS、SREBP-1和PPARα、CPT1的表达。结果与ND组相比,HFD组小鼠体重、体脂、血清TG、TC、HDL水平明显增加;肝脏内脂肪蓄积增加,肝脏SREBP-1c、FAS、ACC1表达增加,而PPARα、CPT1、SIRT1和AMPK表达下降。经DHM处理后,HFD小鼠上述指标发生逆转;但ND小鼠上述指标无明显改变。结论DHM可能通过激活SIRT1-AMPK通路抑制脂质合成,促进脂质分解,改善高脂饮食诱导的肥胖小鼠肝脏脂质沉积。

Dihydromyricin inhibited hepatic lipid deposition induced by high-fat diet in obese mice by activating SIRT1-AMPK pathway

Aim To investigate the effect of dihydromyricetin(DHM)on lipid accumulation in liver of obese mice induced by high fat diet and its mechanism.Methods Sixty C57BL/6J mices were randomly divided into six groups(n=10):①ND group:normal diet,②ND+L-DHM group:normal diet and treatment with low-dose DHM(125 mg·kg^-1·d^-1),③ND+H-DHM group:normal diet and treatment with high-dose DHM(250 mg·kg^-1·d^-1),④HFD group:high-fat diet,and⑤HFD+L-DHM group:high-fat diet and treatment with low-dose DHM,⑥HFD+H-DHM group:high-fat diet and treatment with high-dose DHM.The weight of mice was recorded regularly.At the end of 16 weeks,fasting lipids were detected.Then the body fat weight was calculated.Liver sections were stained with HE and oil red O.The expression of SIRT1,AMPK,ACC,FAS,SREBP-1 and PPAR,CPT1 were detected by fluorescence quantitative PCR and Western blot.Results Compared with ND group,the body weight,body fat,serum TG,TC and HDL levels of HFD group increased.The results of liver staining showed the lipid accumulation in liver increased.The expressions of SREBP-1c,FAS,ACC1 in liver increased,while the expression of PPAR,CPT1,SIRT1 and AMPK decreased.After DHM treatment,the changes of the above indicators in HFD group were reversed,but these indexes of ND mice had no significant change.Conclusions DHM may inhibit lipid synthesis and promote lipid decomposition to improve lipid deposition in liver of obese mice induced by high-fat diet through activating the SIRT1-AMPK pathway.