高脂诱导下胰岛素抵抗和非胰岛素抵抗小鼠糖脂代谢及肠道AKK菌的变化
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摘要
目的对比研究高脂诱导下胰岛素抵抗发生与糖脂代谢及肠道阿克曼菌(akkermansia muciniphila,Akk菌)的差异变化,确定肠道细菌在胰岛素抵抗形成过程中的重要性。方法将35只C57BL/6J小鼠随机分为正常饮食对照组(normal control diet,NCD组)10只,高脂饮食组(high fat diet,HFD组)25只,饮食干预8周后,检测各组小鼠血糖、血脂、口服葡萄糖耐量及胰岛素敏感性的变化,收集各组小鼠粪样。根据HFD组检测指标,从中筛选出胰岛素抵抗(insulin resistance,IR)和非胰岛素抵抗(non-insulin resistance,N-IR)小鼠各10只,分别为IR组和N-IR组。采用基于16SrRNA的实时荧光定量PCR技术分析各组小鼠粪便中Akk菌变化的差异。结果高脂诱导后,与NCD组相比,IR组小鼠体质量、口服葡萄糖耐量实验(OGTT)曲线下面积、胰岛素耐量实验(ITT)曲线下面积、空腹血糖(FBG)、总胆固醇(TC)水平均明显上升,差异有统计学意义(P<0.05),肠道AKK菌丰度明显下降,差异有统计学意义(P<0.05);与IR组相比,N-IR组小鼠体质量、OGTT曲线下面积、ITT曲线下面积、FBG水平明显下降,差异有统计学意义(P<0.05),TC和TG水平有下降趋势,但差异无统计学意义(P>0.05),肠道AKK菌丰度有增加趋势,但差异无统计学意义(P>0.05)。结论高脂诱导下,IR组小鼠糖脂代谢紊乱更加明显,可能与小鼠肠道内AKK菌丰度变化相关。
Objective To compare the changes of glucose resistance and the changes of glucose and lipid metabolism and Akkermansia muciniphila(Akk), and to determine the importance of intestinal bacteria in the formation of insulin resistance. Methods Thirty-five C57 BL/6 J mice were randomly divided into 10 normal control diet(NCD) and 25 high fat diet(HFD) groups. After 8 weeks of dietary intervention, changes in blood glucose, blood lipids, oral glucose tolerance, and insulin sensitivity were measured, and fecal samples from each group were collected. According to the HFD group, 10 mice with insulin resistance(IR) and non-insulin resistance(N-IR) were selected, which were IR group and N-IR group. The difference of Akk bacteria in the feces of each group of mice was analyzed by real-time fluorescent quantitative PCR based on 16 SrRNA. Results After high-fat induction, compared with the NCD group, the body mass, the area under the OGTT curve, the area under the insulin resistance test(ITT) curve, the fasting blood glucose(FBG), and the total cholesterol(TC) level in the IR group increased significantly, and the differences were statistically significant(P<0.05); the abundance of intestinal AKK bacteria decreased significantly, and the difference was statistically significant(P<0.05); compared with the IR group, the body mass, the area under the OGTT curve, the area under the ITT curve, and the FBG level in the N-IR group mice decreased significantly, and the differences were statistically significant(P<0.05). The TC and TG levels showed a downward trend, but the differences were not statistically significant(P>0.05). The abundance of AKK bacteria increased, but the difference was not statistically significant(P>0.05). Conclusion Under the induction of high fat, the disorder of glucose and lipid metabolism in the IR group is more significant, which may be related to the abundance of AKK bacteria in the intestinal tract of mice.
Objective To compare the changes of glucose resistance and the changes of glucose and lipid metabolism and Akkermansia muciniphila(Akk), and to determine the importance of intestinal bacteria in the formation of insulin resistance. Methods Thirty-five C57 BL/6 J mice were randomly divided into 10 normal control diet(NCD) and 25 high fat diet(HFD) groups. After 8 weeks of dietary intervention, changes in blood glucose, blood lipids, oral glucose tolerance, and insulin sensitivity were measured, and fecal samples from each group were collected. According to the HFD group, 10 mice with insulin resistance(IR) and non-insulin resistance(N-IR) were selected, which were IR group and N-IR group. The difference of Akk bacteria in the feces of each group of mice was analyzed by real-time fluorescent quantitative PCR based on 16 SrRNA. Results After high-fat induction, compared with the NCD group, the body mass, the area under the OGTT curve, the area under the insulin resistance test(ITT) curve, the fasting blood glucose(FBG), and the total cholesterol(TC) level in the IR group increased significantly, and the differences were statistically significant(P<0.05); the abundance of intestinal AKK bacteria decreased significantly, and the difference was statistically significant(P<0.05); compared with the IR group, the body mass, the area under the OGTT curve, the area under the ITT curve, and the FBG level in the N-IR group mice decreased significantly, and the differences were statistically significant(P<0.05). The TC and TG levels showed a downward trend, but the differences were not statistically significant(P>0.05). The abundance of AKK bacteria increased, but the difference was not statistically significant(P>0.05). Conclusion Under the induction of high fat, the disorder of glucose and lipid metabolism in the IR group is more significant, which may be related to the abundance of AKK bacteria in the intestinal tract of mice.
引文
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[13] DAO M C,EVERARD A,ARON-WISNEWSKY J,et al.Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity:relationship with gut microbiome richness and ecology[J].Gut,2016,65(3):426-436.
[14] EVERARD A,BELZER C,GEURTS L,et al.Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity[J].Proc Natl Acad Sci USA,2013,110(22):9066-9071.
[2] GLASS C K,OLEFSKY J M.Inflammation and lipid signaling in the etiology of insulin resistance[J].Cell Metab,2012,15(5):635-645.
[3] HALMOS T,SUBA I .Physiological patterns of intestinal microbiota.The role of dysbacteriosis in obesity,insulin resistance,diabetes and metabolic syndrome[J].Orv Hetil,2015,157(1):13-22.
[4] OKUBO H,NAKATSU Y,KUSHIYAMA A,et al.Gut microbiota as a therapeutic target for metabolic disorders [J].Curr Med Chem,2018,25(9):984-1001.
[5] FEDERICO A,DALLIO M,DI S R,et al.Gut microbiota,obesity and metabolic disorders [J].Minerva Gastroenterol Dietol,2017,63(4):337-344.
[6] SEREGIN S S,GOLOVCHENKO N,SCHAF B,et al.NLRP6 protects Il10-/-mice from colitis by limiting colonization of Akkermansia muciniphila [J].Cell Rep,2017,19(4):733-745.
[7] 易金阳,王烨,李琳琳,等.db/db 2型糖尿病模型小鼠肠道多形拟杆菌实时荧光定量 PCR 标准品制备方法的比较研究[J].新疆医科大学学报,2012,35(6):716-720.
[8] 陈明月,王烨,王蟾月,等.从新疆哈萨克族2型糖尿病患者粪便中分离的气单胞菌对小鼠的作用研究[J].中国微生态学杂志,2017,29(2):125-129.
[9] SHERIDAN C.Novo sets sights on obesity market with diabetes drug[J].Nat Biotechnol,2014,32(11):1071-1072.
[10] BELZER C,DE VOS W M.Microbes inside--from diversity to function:the case of Akkermansia[J].ISME J,2012,6(8):1449-1458.
[11] DERRIEN M,BELZER C,VOS W M D.Akkermansia muciniphila and its role in regulating host functions[J].Microb Pathog,2016,9:171-181.
[12] BRAHE L K,LE CHATELIER E,PRIFTI E,et al.Specific gut microbiota features and metabolic markers in postmenopausal women with obesity[J].Nutr Diabetes,2015,5(6):e159.
[13] DAO M C,EVERARD A,ARON-WISNEWSKY J,et al.Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity:relationship with gut microbiome richness and ecology[J].Gut,2016,65(3):426-436.
[14] EVERARD A,BELZER C,GEURTS L,et al.Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity[J].Proc Natl Acad Sci USA,2013,110(22):9066-9071.