钙敏感受体和胆囊收缩素-1受体介导大豆蛋白水解物对小鼠食欲的影响

Effects of CaSR and CCK-1R Mediated Soybean Protein Hydrolysate on Appetite Using Mouse

【目的】探究大豆蛋白水解物(soy protein hydrolysate,SPH)对小鼠食欲的影响及其机制,以期从营养角度为猪采食调控技术的研究提供新思路。【方法】利用胃蛋白酶水解大豆蛋白产生SPH。首先探究灌胃不同浓度SPH对小鼠短期采食量及十二指肠肽钙敏感受体(Calcium sensing receptor,CaSR)、G蛋白偶联受体93(G protein-coupled receptor 93,GPR93)和肽转运受体(Oligopeptide transporter 1,PepT1)基因表达的影响;在此基础上,通过腹腔分别注射CaSR抑制剂NPS2143和外周CCK-1受体(Cholecystokinin-1 receptor,CCK-1R)抑制剂Devazepide,探究SPH是否通过CaSR-CCK-CCK-1R-下丘脑途径抑制机体采食。【结果】灌胃1.5g·kg-1 SPH显著降低小鼠0—1 h采食量(P<0.05)、显著提高十二指肠CaSR的表达(P<0.05);与SPH组相比,SPH+NPS2143组小鼠0—1 h采食量升高,血液CCK水平降低,且均与对照组无差异(0.05<P<0.5)。同时,SPH显著降低小鼠0-1 h胃排空速率,显著提高下丘脑厌食神经因子POMC的基因表达(P<0.05),而SPH+Devazepide组这种作用消失。但灌胃SPH对小肠传输速率和下丘脑促食相关因子NPY(Neuropeptide Y)和AgRP(Agoutirelated peptide)的基因表达均无影响。【结论】十二指肠CaSR介导SPH促进CCK分泌,并通过外周CCK-1R延缓胃排空速率、提高下丘脑厌食神经因子POMC(Pro-opiomelanocortin)的基因表达来抑制食欲。

【Objective】The study aimed to investigate the effects and mechanisms of soy protein hydrolysate(SPH)on the appetite in mice,so as to provide the new frame work guidelines for strategies towards manipulating feed intake in pigs.【Method】In this study,the pepsin was used to hydrolyze soy protein to produce SPH.Firstly,the effects on short-term feed intake and the expressions of duodenal peptide sensing receptors calcium sensing receptor(CaSR),G protein-coupled receptor 93(GPR9)3 and oligopeptide transporter 1(PepT1)were investigated by intragastrically different concentrations of SPH in mice.Based on this,the CaSR inhibitor NPS2143 and the peripheral cholecystokinin-1 receptor(CCK-1 R)inhibitor Devazepide were intraperitoneally injected,respectively,to investigate whether SPH inhibited feed intake by the CASR-CCK-CCK-1 R-hypothalamus pathway.【Result】The amount of 1.5 g·kg-1 SPH reduced the 0-1 h feed intake(P<0.05),and increased the Ca SR expression(P<0.05).Compared with SPH group,the feed intake of SPH+NPS2143 group were increased at 0-1 h,and the plasma CCK levels were decreased,and there were no differences from the control group(0.05<P<0.5).Meanwhile,SPH reduced 0-1 h gastric emptying rate and increased the expression of hypothalamus anorexia nerve factor pro-opiomelanocortin(POMC)(P<0.05),while the effects disappeared in SPH+Devazepide group.However,SPH had no effect on the small intestine transit rate or the expression of the hypothalamic food-promoting factors neuropeptide Y(NPY)and agouti related peptide(AgRP).【Conclusion】CaSR mediated SPH to promote CCK secretion,delayed gastric emptying rate through the peripheral CCK-1 receptor,and improved the expression of hypothalamic anorexia nerve factor POMC to suppress appetite.