短链脂肪酸对高脂饮食诱导肥胖小鼠糖脂代谢紊乱的影响
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摘要
目的探讨短链脂肪酸(SCFA)对高脂饮食(HFD)诱导的肥胖小鼠糖脂代谢紊乱的影响,并从肠上皮屏障功能角度初步探讨可能的作用机制。方法C57BL/6J小鼠40只,随机分为正常饲料对照组(ND)、高脂饮食模型组(HFD)、短链脂肪酸治疗组(HFD+SCFA)组、乳果糖(LA)治疗对照组(HFD+LA),每组10只,高脂饮食造模共14周,第11周开始给药,给药4周后取材。观察体质量、进食量、肝重、肝体比、附睾后脂肪组织脂肪细胞形态及直径;空腹葡萄糖(FBG),空腹血清胰岛素(FINS)及胰岛素抵抗指数(HOMA-IR);血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C);肝组织TG、血清ALT、AST,肝组织病理以及结肠组织病理改变。结果高脂饮食诱导肥胖小鼠给予SCFA干预4周后,体质量、肝重、肝体比、附睾后脂肪细胞直径、FBG、FSI、HOMA-IR、血清TG、血清TC较HFD组均显著降低(P<0.01),且SCFA降低FSI、HOMA-IR、血清TG及TC的作用均优于LA(P<0.01或P<0.05);与HFD组相比,HFD+SCFA组小鼠肝组织TG含量、血清ALT、AST活性均显著降低(P<0.01),肝组织脂肪变性、炎症以及气球样变有显著改善,肝脏活动度积分(NAS)显著降低(P<0.01);SCFA干预可显著改善高脂饮食诱导的小鼠结肠上皮损伤、腺体排列紊乱、炎症细胞浸润等病理学改变。结论短链脂肪酸可有效降低高脂饮食诱导肥胖小鼠的体质量、改善血糖血脂代谢紊乱以及脂肪肝;降低肠道炎性反应,提高肠上皮屏障功能是可能的作用机制之一。
Objective To observe the effects of short chain fatty acids(SCFAs)on metabolism of glucose and lipid in obese mice induced by high fat diet(HFD),and to investigate the possible mechanisms from the perspective of intestinal epithelial barrier function.Methods Forty C57 BL/6 J mice were equally randomly divided into normal diet(ND)group,HFD model group,SCFAs treatment(HFD+SCFAs)group and lactulose(LA)treatment(HFD+LA)group.Mice were fed a HFD for 14 weeks,and treated with corresponding drugs or distilled water since week 10.After 4-week treatment,mice were sacrificed for observing body weight,food intake,liver weight,ratio of liver weight to body weight,morphology and diameter of adipocytes after epididymis,fasting plasma glucose(FBG),fasting serum insulin(FINS),homeostatic model assessment insulin resistance(HOMA-IR),serum triglyceride(TG),serum cholesterol(TC),low density lipoprotein,hepatic TG,serum alanine aminotransferase,aspartate aminotransferase,and hepatic and colonic tissue pathological changes.Results The body weight,liver weight,ratio of liver weight to body weight,FBG,FSI,HOMAIR,serum TG,serum TC and hepatic TG in HFD+SCFAs group were significantly lower than those in the HFD group(P<0.01).SCFAs was superior to LA in reducing FSI,HOMA-IR,serum TG,serum TC,and hepatic TG(P<0.01 or P<0.05).Moreover,hepatic steatosis,inflammation and ballooning were significantly improved in HFD+SCFAs group than those in HFD group,and disease activity score was decreased(P<0.01).SCFAs intervention could significantly improve colonic pathology,including colonic epithelial damage,glandular disorder and inflammatory cell infiltration induced by HFD.Conclusion SCFAs can effectively reduce body weight,improve the metabolism of glucose and lipid and decrease hepatic fat deposition in obese mice induced by HFD.Reducing intestinal inflammatory response and enhancing intestinalepithelial barrier function maybe one of the possible mechanisms.
Objective To observe the effects of short chain fatty acids(SCFAs)on metabolism of glucose and lipid in obese mice induced by high fat diet(HFD),and to investigate the possible mechanisms from the perspective of intestinal epithelial barrier function.Methods Forty C57 BL/6 J mice were equally randomly divided into normal diet(ND)group,HFD model group,SCFAs treatment(HFD+SCFAs)group and lactulose(LA)treatment(HFD+LA)group.Mice were fed a HFD for 14 weeks,and treated with corresponding drugs or distilled water since week 10.After 4-week treatment,mice were sacrificed for observing body weight,food intake,liver weight,ratio of liver weight to body weight,morphology and diameter of adipocytes after epididymis,fasting plasma glucose(FBG),fasting serum insulin(FINS),homeostatic model assessment insulin resistance(HOMA-IR),serum triglyceride(TG),serum cholesterol(TC),low density lipoprotein,hepatic TG,serum alanine aminotransferase,aspartate aminotransferase,and hepatic and colonic tissue pathological changes.Results The body weight,liver weight,ratio of liver weight to body weight,FBG,FSI,HOMAIR,serum TG,serum TC and hepatic TG in HFD+SCFAs group were significantly lower than those in the HFD group(P<0.01).SCFAs was superior to LA in reducing FSI,HOMA-IR,serum TG,serum TC,and hepatic TG(P<0.01 or P<0.05).Moreover,hepatic steatosis,inflammation and ballooning were significantly improved in HFD+SCFAs group than those in HFD group,and disease activity score was decreased(P<0.01).SCFAs intervention could significantly improve colonic pathology,including colonic epithelial damage,glandular disorder and inflammatory cell infiltration induced by HFD.Conclusion SCFAs can effectively reduce body weight,improve the metabolism of glucose and lipid and decrease hepatic fat deposition in obese mice induced by HFD.Reducing intestinal inflammatory response and enhancing intestinalepithelial barrier function maybe one of the possible mechanisms.
引文
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[2]杨蕊旭,周达,范建高.靶向肠道菌群代谢产物防治非酒精性脂肪性肝病.实用肝脏病杂志,2017,20:643-646.
[3]Tan J,McKenzie C,Potamitis M,et al.The role of short chain fatty acids in health and disease.Adv Immunol,2014,121:91-119.
[4]Chambers ES,Viardot A,Psichas A,et al.Effects of targeted delivery of propionate to the human colon on appetite regulation,body weight maintenance and adiposity in overweight adults.Gut,2015,64:1744-1754.
[5]Lin HV,Frassetto A,Kowalik EJ,Jr.,et al.Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms.PLoS One,2012,7:e35240.
[6]den Besten G,Bleeker A,Gerding A,et al.Short-Chain Fatty Acids Protect Against High-fat Diet-induced Obesity via a PPARγ-Dependent Switch From Lipogenesis to Fat Oxidation.Diabetes,2015,64:2398-2408.
[7]Kleiner DE,Brunt EM,Van Natta M,et al.Design and validation of a histological scoring system for nonalcoholic fatty liver disease.Hepatology,2005,41:1313-1321.
[8]Brown JM,Hazen SL.Targeting of microbe-derived metabolites to improve human health:The next frontier for drug discovery.J Biol Chem,2017,292:8560-8568.
[9]Barroso E,Montilla A,Corzo N,et al.Effect of lactulosederived oligosaccharides on intestinal microbiota during the shift between media with different energy contents.Food Res Int,2016,89:302-308.
[10]Schachter J,Martel J,Lin CS,et al.Effects of obesity on depression:Arole for inflammation and the gut microbiota.Brain Behav Immun,2017,S0889-1591:30415-30424.
[11]Chen T,Kim CY,Kaur A,et al.Dietary fibre-based SCFAmixtures promote both protection and repair of intestinal epithelial barrier function in a Caco-2 cell model.Food Funct,2017,8:1166-1173.