关键词: AMP活化蛋白激酶(AMPK), 哺乳动物雷帕霉素靶蛋白(mTOR), 自噬, 益生菌, 脂代谢紊乱

Abstract: Objective To study the effect of probiotics on lipid metabolism disorder in obese mice induced by high-fat and high-sucrose diet. Methods C57BL/6J mice were randomly divided into control group, model group (high-fat and high-sucrose feed), probiotics group (2×10⁹ CFU probiotics), inhibitor group (AMPK inhibitor dorsomerphin, 10 mg/kg) and probiotics+inhibitor group, with 10 mice in each group.Hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue; Oil Red O staining was used to observe the accumulation of fat in liver tissue; Western blot was used to detect the expression of pathway proteins. Results Compared with control group, in model animals, lipid vacuoles were found in liver tissue, the nuclear staining was deepened, a large amount of fat accumulation and autophagy bodies were reduced, lipid metabolism indexes (TC, TAG,LDL) were raised. Expression of lipid metabolism protein SREBP-1c and mTOR phosphorylation were all increased(P＜0.05); Lipid metabolism indexes HDL, expression of autophagy related protein LC3 and Beclin1 and AMPK phosphorylation of model group were inhibited(P＜0.05). Compared with model group, the lipid vacuoles and fat accumulation in probiotics group were alleviated, and more autophagosomes were observed, TC, TAG, LDL, SREBP-1c expression and mTOR phosphorylation were decreased(P＜0.05), expression of HDL, LC3 and Beclin1 and AMPK phosphorylation of probiotics group were higher (P＜0.05); The number of lipid vacuoles increased and became larger, the accumulation of fat increased while the autophagy decreased, TC, TAG, LDL, SREBP-1c expression level and mTOR phosphorylation level were higher (P＜0.05), expression of HDL, LC3 and Beclin1 protein and AMPK phosphorylation of inhibitor group were inhibited(P＜0.05). The inhibitor group was compared with the model group, the probiotic+inhibitor group was compared with the probiotic group, the lipid vacuoles and fat accumulation in the liver tissue were higher, and the autophagy body counting was reduced, expression of TC, TAG, LDL, SREBP-1c and mTOR phosphorylation were higher (P＜0.05), expression of HDL, LC3 and Beclin1 protein and AMPK phosphorylation were decreased(P＜0.05). Conclusions Probiotics may activate AMPK pathway and then negatively regulate mTOR pathway, promote hepatocyte autophagy and improve lipid metabolism of obese mice induced by high-fat and high-sucrose diet.

Key words: AMP-activated protein kinase(AMPK), mammalian target of rapamycin(mTOR), autophagy, probiotics, lipid metabolism disorder