乳酸片球菌AS185调节高脂高糖饮食诱导的代谢综合征

Pediococcus acidilactici AS185 Improves Metabolic Syndrome Induced by a High-Fat and High-Fructose Diet

目的:研究乳酸片球菌(Pediococcus acidilactici)AS185对代谢综合征小鼠的调节作用,并探讨其作用机制。方法:高脂高糖饮食诱导小鼠代谢综合征造模(6周),灌胃乳酸片球菌AS185,每天1次,连续8周,通过测量体质量、血糖浓度、血脂和血清炎症因子水平并进行Western blot检测,评价乳酸片球菌AS185菌株改善代谢综合征的作用和机制。结果:灌胃乳酸片球菌AS185可降低高脂高糖饮食诱导的代谢综合征小鼠血清中总胆固醇、甘油三酯、低密度脂蛋白胆固醇、肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6、胰岛素、空腹血糖、游离脂肪酸、C-反应蛋白和脂多糖水平。Western blot分析结果表明,乳酸片球菌AS185抑制了高脂高糖诱导的核因子κB蛋白的活化、Toll样受体4(Toll-like receptor 4,TLR4)及髓样分化因子(myeloid differentiation factor 88,MyD88)蛋白的表达,抑制炎症通路和炎症因子的表达。乳酸片球菌AS185通过激活肝组织中肝激酶B1(liver kinase B1,LKB1)和腺苷酸活化蛋白激酶(adenylate activated protein kinase,AMPK)的表达,提高磷酸化AMPK和磷酸化乙酰辅酶A羧化酶蛋白表达,并抑制固醇调节元件结合蛋白1c蛋白的表达,调节脂类代谢通路。结论:乳酸片球菌AS185通过激活TLR4-MyD88-NF-κB通路,降低小鼠血清中的炎症因子的水平,并通过激活LKB1-AMPK信号通路,改善代谢综合征小鼠的血脂紊乱,调节高脂高糖饮食导致的代谢综合征。

Objective:To study the regulatory effect and underlying mechanism of Pediococcus acidilactici AS185 on metabolic syndrome(MS)in mice.Methods:ICR mice were given a high-fat and high-fructose diet once a day for 6 consecutive weeks to establish an MS model,and AS185 was administered by gavage to the animals once a day from week 7 to 14.The body mass,blood glucose,blood lipid and serum inflammatory factors were determined and Western blot was performed to analyze the expression of relevant proteins.Results:The administration of P.acidilactici AS185 could reduce the serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,insulin(INS),fasting blood glucose(FBG),free fatty acid(FFA),C-reactive protein(CRP)and lipopolysaccharide(LPS)in the mouse model.Western blot analysis showed that P.acidilactici AS185 inhibited the activation of nuclear factor(NF)-κB,and the expression of Toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88),suppressed inflammatory signaling pathways and the expression of inflammatory factors in the high-fat and high-fructose diet-fed mice.Moreover,it activated liver kinase B1(LKB1)and the expression of adenylate activated protein kinase(AMPK),thereby enhancing the expression of phosphorylated AMPK(p-AMPK)and phosphorylated acetyl-CoA carboxylase(p-ACC),down-regulating the expression of sterol regulatory element-binding protein-1c(SREBP-1c)and finally regulating the lipid metabolism pathway.Conclusion:P.acidilactici AS185 can improve high-fat and high-fructose diet-induced metabolic syndrome in mice by activating the TLR4-MyD88-NF-κB pathway to regulate inflammatory factor levels,and activating the LKB1-AMPK signaling pathway to improve blood lipid disorders.