植物乳杆菌通过调节肠道短链脂肪酸水平缓解代谢综合征
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摘要
目的:探究植物乳杆菌对高糖高脂饮食导致的代谢综合征的调控效果及可能机制。方法:利用高糖高脂饮食的大鼠模型,评价植物乳杆菌对代谢综合征的缓解作用;具体包括:检测大鼠血清中血糖、血脂等代谢指标和肝脏抗氧化能力,对肝脏、十二指肠及胰岛进行组织病理学分析,测定大鼠粪便中的短链脂肪酸含量。结果:高糖高脂饮食引发了一系列代谢紊乱,补充植物乳杆菌对代射紊乱具有一定的缓解作用,但存在菌株差异性;进一步分析表明,植物乳杆菌CCFM591可调节大鼠血糖-胰岛素稳态,减轻胰岛和小肠组织病变,同时提高大鼠粪便中短链脂肪酸的含量。结论:植物乳杆菌CCFM591可能通过调节肠道短链脂肪酸水平实现对大鼠高糖高脂饮食导致的代谢综合征的缓解作用。
Purpose:To investigate the regulatory effect of Lactobacillus plantarum on metabolic syndrome induced by high-fat-high-sucrose(HFHS) diet in rats and its possible mechanism of action.Methods:Serum metabolic parameters such as lipids and glucose and liver antioxidant status were determined;histopathological analysis was performed for liver,duodenum and pancreatic islet tissues and the levels of short-chain fatty acids(SCFAs) in rat faces were also examined.Results:HFHS-fed rat developed hallmark features of metabolic syndrome,and L.plantarum attenuated the development of metabolic syndrome but the effect varied among strains.Further analysis demonstrated that supplementation with L.plantarum CCFM591 significantly enhanced blood glucose-insulin homeostasis,attenuated the pathological changes in pancreatic islet and small intestinal tissues,and elevated the level of SCFAs in stool.Conclusion:L.plantarum CCFM591 may ameliorate the progression of HFHS diet-induced metabolic syndrome by modulating the levels of intestinal SCFAs.
Purpose:To investigate the regulatory effect of Lactobacillus plantarum on metabolic syndrome induced by high-fat-high-sucrose(HFHS) diet in rats and its possible mechanism of action.Methods:Serum metabolic parameters such as lipids and glucose and liver antioxidant status were determined;histopathological analysis was performed for liver,duodenum and pancreatic islet tissues and the levels of short-chain fatty acids(SCFAs) in rat faces were also examined.Results:HFHS-fed rat developed hallmark features of metabolic syndrome,and L.plantarum attenuated the development of metabolic syndrome but the effect varied among strains.Further analysis demonstrated that supplementation with L.plantarum CCFM591 significantly enhanced blood glucose-insulin homeostasis,attenuated the pathological changes in pancreatic islet and small intestinal tissues,and elevated the level of SCFAs in stool.Conclusion:L.plantarum CCFM591 may ameliorate the progression of HFHS diet-induced metabolic syndrome by modulating the levels of intestinal SCFAs.
引文
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[34]YONG Z,DU R,WANG L,et al.The antioxidative effects of probiotic Lactobacillus casei Zhang on the hyperlipidemic rats[J].European Food Research&Technology,2010,231(1):151-158.DOI:10.1007/s00217-010-1255-1.
[35]DEMIGNéC,MORAND C,LEVRAT M A,et al.Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes[J].British Journal of Nutrition,1995,74(2):209-219.DOI:10.1079/Bjn19950124.
[36]CANFORA E E,JOCKEN J W,BLAAK E E.Short-chain fatty acids in control of body weight and insulin sensitivity[J].Nature Reviews Endocrinology,2015,11(10):577-591.DOI:10.1038/nrendo.2015.128.
[37]GAO Z G,YIN J,ZHANG J,et al.Butyrate improves insulin sensitivity and increases energy expenditure in mice[J].Diabetes,2009,58(7):1509-1517.DOI:10.2337/db08-1637.
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[39]YADAV H,LEE J H,LLOYD J,et al.Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion[J].Journal of Biological Chemistry,2013,288(35):25088-25097.DOI:10.1074/jbc.M113.452516.
[40]VENTER C S,VORSTER H H,CUMMINGS J H.Effects of dietary propionate on carbohydrate and lipid metabolism in healthy volunteers[J].American Journal of Gastroenterology,1990,85(5):549-553.
[2]LEY R.Microbial ecology:human gut microbes associated with obesity[J].Nature,2006,444:1022-1023.DOI:10.1038/nature4441022a.
[3]DUCA F A,SAKAR Y,LEPAGE P,et al.Replication of obesity and associated signaling pathways through transfer of microbiota from obese-prone rats[J].Diabetes,2014,63(5):1624-1636.DOI:10.2337/db13-1526.
[4]TURNBAUGH P J,LEY R E,MAHOWALD M A,et al.An obesityassociated gut microbiome with increased capacity for energy harvest[J].Nature,2006,444:1027-1031.DOI:10.1038/nature05414.
[5]DAVID L A,MAURICE C F,CARMODY R N,et al.Diet rapidly and reproducibly alters the human gut microbiome[J].Nature,2014,505:559-563.DOI:10.1038/nature12820.
[6]NICHOLSON J K,HOLMES E,KINROSS J,et al.Host-gut microbiota metabolic interactions[J].Science,2012,336:1262-1267.DOI:10.1126/science.1223813.
[7]WANG J,TANG H,ZHANG C,et al.Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice[J].ISME Journal,2015,9(1):1-15.DOI:10.1038/ismej.2014.99.
[8]伍佩英.β-葡聚糖对实验性代谢综合征改善作用及其机制研究[D].上海:第二军医大学,2007:14.
[9]夏燕萍,陈刚,俞茂华.高糖高脂饮食诱导建立SD大鼠代谢综合征模型[J].中国现代医学杂志,2009,19(17):2607-2609.
[10]沈成义,闫振成,祝之明.Wistar大鼠代谢综合征动物模型的构建及其特征分析[J].川北医学院学报,2007,22(6):526-529.
[11]陈津津,王韧,李晓芳,等.高脂饮食诱导代谢综合征模型建立[J].中国临床保健杂志,2011,14(2):160-162.
[12]GARIDOU L,POMIéC,KLOPP P,et al.The gut microbiota regulates intestinal CD4 T cells expressing RORγt and controls metabolic disease[J].Cell Metabolism,2015,22(1):100-112.DOI:10.1016/j.cmet.2015.06.001.
[13]BI Y,LI C,LIU L,et al.IL-17A-dependent gut microbiota is essential for regulating diet-induced disorders in mice[J].Science Bulletin,2017,62(15):1052-1063.DOI:10.1016/j.scib.2017.07.011.
[14]MACFARLANE G T,MACFARLANE S.Bacteria,colonic fermentation,and gastrointestinal health[J].Journal of Aoac International,2012,95(1):50-60.DOI:10.5740/jaoacint.SGE_Macfarlane.
[15]CUMMINGS J H,POMARE E W,BRANCH W J,et al.Short chain fatty acids in human large intestine,portal,hepatic and venous blood[J].Gut,1987,28(10):1221-1227.DOI:10.1136/gut.28.10.1221.
[16]WICHMANN A,ALLAHYAR A,GREINER T U,et al.Microbial modulation of energy availability in the colon regulates intestinal transit[J].Cell Host&Microbe,2013,14(5):582-590.DOI:10.1016/j.chom.2013.09.012.
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[18]FROST G,SLEETH M L,SAHURIARISOYLU M,et al.The shortchain fatty acid acetate reduces appetite via a central homeostatic mechanism[J].Nature Communications,2014,5:3611.DOI:10.1038/ncomms4611.
[19]MCNELIS J C,YUN S L,MAYORAL R,et al.GPR43 potentiates beta cell function in obesity[J].Diabetes,2015,64(9):3203-3217.DOI:10.2337/db14-1938.
[20]TOLHURST G,HEFFRON H,LAM Y S,et al.Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2[J].Diabetes,2012,61(2):364-371.DOI:10.2337/db11-1019.
[21]李向菲.产胞外多糖乳酸菌对2型糖尿病的干预及其机制研究[D].无锡:江南大学,2016:36.
[22]SAMUEL B S,GORDON J I.A humanized gnotobiotic mouse model of host-archaeal-bacterial mutualism[J].Proceedings of the National Academy of Sciences of the United States of America,2006,103(26):10011-10016.DOI:10.1073/pnas.0602187103.
[23]WANG Gang,LI Xiangfei,ZHAO Jianxin,et al.Lactobacillus casei CCFM419 attenuates type 2 diabetes via a gut microbiota dependent mechanism[J].Food&Function,2017,8(9):3155-3164.DOI:10.1039/c7fo00593h.
[24]KONDO S,XIAO J Z,SATOH T,et al.Antiobesity effects of Bifdobacterium breve strain B-3 supplementation in a mouse model with high-fat diet-induced obesity[J].Bioscience,Biotechnology,and Biochemistry.,2010,74(8):1656-1661.DOI:10.1271/bbb.100267.
[25]AN H M,PARK S H,LEE D K,et al.Antiobesity and lipid-lowering effects of Bifdobacterium spp.in high fat diet-induced obese rats[J].Lipids in Health and Disease,2011,10:116.
[26]CHEN Jinjin,WANG Ren,LI Xiaofang,et al.Bifidobacterium longum supplementation improved high-fat-fed-induced metabolic syndrome and promoted intestinal Reg I gene expression[J].Experimental Biology&Medicine,2011,236(7):823-831.DOI:10.1258/ebm.2011.010399.
[27]HSIEH F C,LEE C L,CHAI C Y,et al.Oral administration of Lactobacillus reuteri GMNL-263 improves insulin resistance and ameliorates hepatic steatosis in high fructose-fed rats[J].Nutrition&Metabolism,2013,10(1):35.DOI:10.1186/1743-7075-10-35.
[28]KIM S W,PARK K Y,KIM B,et al.Lactobacillus rhamnosus GGimproves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production[J].Biochemical&Biophysical Research Communications,2013,431(2):258-263.DOI:10.1016/j.bbrc.2012.12.121.
[29]ZHU W,GREGORY J C,ORG E,et al.Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk[J].Cell,2016,165(1):111-124.DOI:10.1016/j.cell.2016.02.011.
[30]YANG Bo,CHEN Haiqin,GU Zhennan,et al.Synthesis of conjugated linoleic acid by the linoleate isomerase complex in food-derived lactobacilli[J].Journal of Applied Microbiology,2014,117(2):430-439.DOI:10.1111/jam.12524.
[31]XIE Ning,CUI Yi,YIN Yani,et al.Effects of two Lactobacillus strains on lipid metabolism and intestinal microflora in rats fed a highcholesterol diet[J].BMC Complementary&Alternative Medicine,2011,11(1):53.DOI:10.1186/1472-6882-11-53.
[32]LI Chuan,NIE Shaoping,DING Qiao,et al.Cholesterol-lowering effect of Lactobacillus plantarum NCU116 in a hyperlipidaemic rat model[J].Journal of Functional Foods,2014,8:340-347.DOI:10.1016/j.jff.2014.03.031.
[33]YADAV H,JAIN S,SINHA P R.Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats[J].Nutrition,2007,23(1):62-68.DOI:10.1016/j.nut.2006.09.002.
[34]YONG Z,DU R,WANG L,et al.The antioxidative effects of probiotic Lactobacillus casei Zhang on the hyperlipidemic rats[J].European Food Research&Technology,2010,231(1):151-158.DOI:10.1007/s00217-010-1255-1.
[35]DEMIGNéC,MORAND C,LEVRAT M A,et al.Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes[J].British Journal of Nutrition,1995,74(2):209-219.DOI:10.1079/Bjn19950124.
[36]CANFORA E E,JOCKEN J W,BLAAK E E.Short-chain fatty acids in control of body weight and insulin sensitivity[J].Nature Reviews Endocrinology,2015,11(10):577-591.DOI:10.1038/nrendo.2015.128.
[37]GAO Z G,YIN J,ZHANG J,et al.Butyrate improves insulin sensitivity and increases energy expenditure in mice[J].Diabetes,2009,58(7):1509-1517.DOI:10.2337/db08-1637.
[38]AOKI R,KAMIKADO K,SUDA W,et al.A proliferative probiotic Bifidobacterium strain in the gut ameliorates progression of metabolic disorders via microbiota modulation and acetate elevation[J].Scientific Reports,2017,7:43522.DOI:10.1038/srep43522.
[39]YADAV H,LEE J H,LLOYD J,et al.Beneficial metabolic effects of a probiotic via butyrate-induced GLP-1 hormone secretion[J].Journal of Biological Chemistry,2013,288(35):25088-25097.DOI:10.1074/jbc.M113.452516.
[40]VENTER C S,VORSTER H H,CUMMINGS J H.Effects of dietary propionate on carbohydrate and lipid metabolism in healthy volunteers[J].American Journal of Gastroenterology,1990,85(5):549-553.