黄芪多糖对高糖高脂饮食模型大鼠肠道甜味受体通路的影响
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摘要
目的:探讨黄芪多糖对高糖高脂饮食模型大鼠肠道甜味受体味觉受体第一家族成员2(T1R2)/味觉受体第一家族成员3(T1R3)通路的影响。方法:SD大鼠随机分为正常组、高糖高脂组和黄芪多糖组。高糖高脂饲料组和黄芪多糖组大鼠给予高糖高脂饲料喂养16周,期间黄芪多糖组大鼠每日给予0. 7 g·kg~(-1)的APS灌胃8周。采集大鼠血清测定空腹血糖,总胆固醇(TC),甘油三酯(TG),高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)含量;采集大鼠肠道组织,采用实时荧光定量聚合酶链式反应(Real-time PCR)检测甜味受体通路T1R2,T1R3,α-味导素(Gαgust)和顺时受体电位阳离子通道5(TRPM5)以及胰高血糖素原(PG) mRNA的表达水平;蛋白免疫印迹法(Western blot)检测T1R2,Gαgust和胰高血糖素样肽(GLP-1)蛋白表达水平。结果:与正常组比较,高糖高脂组大鼠血清TC,TG和LDL-C含量明显升高,HDL-C含量明显降低(P <0. 05);肠道甜味受体通路中的T1R2,Gαgust和PG mRNA表达水平明显降低(P <0. 05);与高糖高脂组比较,黄芪多糖组大鼠血清TC,TG,LDL-C含量明显降低,HDL-C含量明显升高(P <0. 05),肠道甜味受体通路分子T1R2,T1R3,Gαgust,TRPM5以及PG mRNA表达水平明显升高(P <0. 05),T1R2,Gαgust和GLP-1蛋白表达明显升高;与模型组比较,黄芪多糖组T1R3 mRNA表达及T1R2,Gαgust,GLP-1蛋白表达水平均明显降低(P <0. 05)。结论:黄芪多糖可改善高糖高脂饮食模型大鼠脂代谢紊乱和肠道甜味受体通路的损伤。
Objective: To observe the effect of astragalus polysaccharide( APS) on taste receptor 1 member 2( T1R2)/taste receptor 1 member 3( T1R3) sweet taste receptor pathway in intestine of rat model induced by high-sugar and high-fat diet. Method: SD rats were randomly divided into normal group,high-sugar and high-fat group and astragalus polysaccharide group. Rats in high-sugar and high-fat group and astragalus polysaccharide groups were fed with high-sugar and high-fat diet for 16 weeks, while rats in astragalus polysaccharide group were fed with APS( 0. 7 g·kg~(-1),per day) for 8 weeks during this period. Serum samples were collected to determine the levels of fasting blood glucose,total cholesterol( TC),triglyceride( TG),highdensity lipoprotein cholesterol( HDL-C) and low-density lipoprotein cholesterol( LDL-C). Intestinum tenue was collected to determine mRNA expressions of T1R2/T1R3,α-gustducin( Gα gust),transient receptor potential cation channel subfamily member 5( TRPM5) and proglucagon( PG) gene by Real-time PCR,and protein expressions of T1R2,Gα gust and glucagon-like peptide-1( GLP-1) protein by Western blot. Result: Rats in high-sugar and high-fat group had significantly higher levels of TC,TG and LDL-C,and lower HDL-C level in serum than those in normal group( P < 0. 05). Moreover,the expression levels of sweet receptor pathway molecules,including T1R2,Gα gust and PG genes in intestine,were significantly down-regulated in high-sugar and high-fat group( P < 0. 05). Rats in astragalus polysaccharide group had significantly lower levels of TC,TG and LDL-C,and higher HDL-C level in serum than those in high-sugar and high-fat group( P < 0. 05). The expression levels of T1R2,T1R3,Gα gust,TRPM5 and PG genes in intestine were significantly up-regulated in astragalus polysaccharide group( P < 0. 05). The trend of T1R2,Gα gust and GLP-1 protein expressions was consistent with that of T1R2,Gα gust and GLP-1 mRNA expressions. Protein expressions of T1R2,Gα gust and GLP-1 and mRNA expression of T1R3 were significantly lower in astragalus polysaccharide group than those of control group( P < 0. 05). Conclusion: APS could improve disturbance of lipid metabolism and impairment of intestinal sweet taste receptor pathway for rat model induced by high-sugar and high-fat diet.
Objective: To observe the effect of astragalus polysaccharide( APS) on taste receptor 1 member 2( T1R2)/taste receptor 1 member 3( T1R3) sweet taste receptor pathway in intestine of rat model induced by high-sugar and high-fat diet. Method: SD rats were randomly divided into normal group,high-sugar and high-fat group and astragalus polysaccharide group. Rats in high-sugar and high-fat group and astragalus polysaccharide groups were fed with high-sugar and high-fat diet for 16 weeks, while rats in astragalus polysaccharide group were fed with APS( 0. 7 g·kg~(-1),per day) for 8 weeks during this period. Serum samples were collected to determine the levels of fasting blood glucose,total cholesterol( TC),triglyceride( TG),highdensity lipoprotein cholesterol( HDL-C) and low-density lipoprotein cholesterol( LDL-C). Intestinum tenue was collected to determine mRNA expressions of T1R2/T1R3,α-gustducin( Gα gust),transient receptor potential cation channel subfamily member 5( TRPM5) and proglucagon( PG) gene by Real-time PCR,and protein expressions of T1R2,Gα gust and glucagon-like peptide-1( GLP-1) protein by Western blot. Result: Rats in high-sugar and high-fat group had significantly higher levels of TC,TG and LDL-C,and lower HDL-C level in serum than those in normal group( P < 0. 05). Moreover,the expression levels of sweet receptor pathway molecules,including T1R2,Gα gust and PG genes in intestine,were significantly down-regulated in high-sugar and high-fat group( P < 0. 05). Rats in astragalus polysaccharide group had significantly lower levels of TC,TG and LDL-C,and higher HDL-C level in serum than those in high-sugar and high-fat group( P < 0. 05). The expression levels of T1R2,T1R3,Gα gust,TRPM5 and PG genes in intestine were significantly up-regulated in astragalus polysaccharide group( P < 0. 05). The trend of T1R2,Gα gust and GLP-1 protein expressions was consistent with that of T1R2,Gα gust and GLP-1 mRNA expressions. Protein expressions of T1R2,Gα gust and GLP-1 and mRNA expression of T1R3 were significantly lower in astragalus polysaccharide group than those of control group( P < 0. 05). Conclusion: APS could improve disturbance of lipid metabolism and impairment of intestinal sweet taste receptor pathway for rat model induced by high-sugar and high-fat diet.
引文
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[15] Smith K R,Hussain T,Karimian A E,et al. Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity[J].Am J Physiol Endocrinol Metab,2016,310(8):688-698.
[16] FENG R,QIAN C,LIU Q,et al. Expression of sweet taste receptor and gut hormone secretion in modelled type 2 diabetes[J]. Gen Comp Endocrinol,2017,252(26):142-149.
[17] Kristina I R,Ellen M C,Allison C S. How non-nutritive sweeteners influence hormones and health[J]. Trends Endocrinol Metab,2018,29(7):455-467.
[18] Assadi-Porter F M,Radek J,RAO H,et al. Multimodal ligand binding studies of human and mouse G-coupled taste receptors to correlate their species-specific sweetness tasting troperties[J]. Molecules,2018,23(10):2531-2546.
[2]钱蔷,莫朝晖.二甲双胍对2型糖尿病大鼠肠道L细胞及味觉受体的影响[J].临床和实验医学杂志,2015,14(8):613-616.
[3]袁前发,唐思梦,陈思羽,等.黄芪多糖对非酒精性脂肪肝病大鼠的治疗作用[J].第二军医大学学报,2018,39(5):573-578.
[4]陈思羽,袁前发,王颖,等.黄芪多糖对高脂血症大鼠糖脂代谢及胰腺组织病理改变的影响[J].广东药科大学学报,2018,34(4):457-461.
[5]唐思梦,杨泽民,陈伟强,等.黄芪多糖保护胰岛β细胞改善大鼠2型糖尿病[J].第二军医大学学报,2017,38(4):482-487.
[6] GU C, ZENG Y, TANG Z, et al. Astragalus polysaccharides affect insulin resistance by regulating the hepatic SIRT1-PGC-1α/PPARα-FGF21 signaling pathway in male sprague dawley rats undergoing catchup growth[J]. Mol Med Rep,2015,12(5):6451-6460.
[7] Lee S J,Depoortere I,Hatt H. Therapeutic potential of ectopic olfactory and taste receptors[J]. Nat Rev Drug Discov,2018,30(11):2140-2159.
[8] Holzer P. Acid sensing by visceral afferent neurones[J]. Acta Physiol,2011,201(1):63-75.
[9] Kanako I,Norio H,Kazuki S,et al. Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion[J].Endocrinology,2015,156(3):837-846.
[10] HAN P F,Bagenna B,FU M H. The sweet taste signalling pathways in the oral cavity and the gastrointestinal tract affect human appetite and food intake a review[J]. Int J Food Sci Nutr,2018,30(1):1-11.
[11] Holst J J. The physiology of glucagon-like peptide 1[J].Physiol Rev,2007,87(4):1409-1439.
[12] Zaza K,Bedrich M,Robert F M. T1r3 and alphagustducin in gut regulate secretion of glucagon-like peptide-1[J]. Ann N Y Acad Sci,2009,1170(1):91-94.
[13] Murovets V O,Bachmanov A A,Travnikov S V,et al.The involvement of the T1R3 receptor protein in the control of glucose metabolism in mice at different levels of glycemia[J]. J Evol Biochem Physiol,2014,50(4):334-344.
[14] Jang H J,Zaza K,Michael J T,et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1[J]. Proc Natl Acad Sci USA,2007,104(38):15069-15074.
[15] Smith K R,Hussain T,Karimian A E,et al. Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity[J].Am J Physiol Endocrinol Metab,2016,310(8):688-698.
[16] FENG R,QIAN C,LIU Q,et al. Expression of sweet taste receptor and gut hormone secretion in modelled type 2 diabetes[J]. Gen Comp Endocrinol,2017,252(26):142-149.
[17] Kristina I R,Ellen M C,Allison C S. How non-nutritive sweeteners influence hormones and health[J]. Trends Endocrinol Metab,2018,29(7):455-467.
[18] Assadi-Porter F M,Radek J,RAO H,et al. Multimodal ligand binding studies of human and mouse G-coupled taste receptors to correlate their species-specific sweetness tasting troperties[J]. Molecules,2018,23(10):2531-2546.