氨基酸調(diào)控畜禽采食的研究進(jìn)展

余健劍 束 剛 江青艷

(華南農(nóng)業(yè)大學(xué)動(dòng)物科學(xué)學(xué)院,廣州 510642)

在動(dòng)物生產(chǎn)中,采食量是影響動(dòng)物生產(chǎn)性能的重要因素。提高采食量有利于發(fā)揮動(dòng)物的生產(chǎn)潛能,而一些不良因素如疾病或熱應(yīng)激等往往會(huì)導(dǎo)致動(dòng)物采食量降低,生產(chǎn)性能下降。研究表明,飼糧中蛋白質(zhì)或氨基酸水平對(duì)動(dòng)物采食的影響極為重要,下丘腦的采食調(diào)控中樞可以通過(guò)神經(jīng)與體液通路監(jiān)測(cè)飼糧中攝入的蛋白質(zhì)和氨基酸水平[1-2],從而調(diào)節(jié)動(dòng)物的食欲。近年來(lái)的一系列研究發(fā)現(xiàn),一些氨基酸可以通過(guò)中樞和外周機(jī)制調(diào)節(jié)畜禽的采食量。

1 亮氨酸對(duì)畜禽采食的調(diào)控作用

亮氨酸屬于支鏈氨基酸,是必需氨基酸之一,也是唯一的生酮氨基酸。腦室注射亮氨酸研究結(jié)果表明,亮氨酸具有明顯的攝食調(diào)節(jié)效應(yīng)。Cota等[2]對(duì)大鼠中樞注射 1.1μg的 L-亮氨酸,觀察到大鼠采食量顯著減少,同時(shí)促食欲神經(jīng)肽 Y(NPY)和刺鼠相關(guān)蛋白(AgRP)的表達(dá)量顯著下降。Morrison等[3]給大鼠飼喂低蛋白質(zhì)飼糧,發(fā)現(xiàn)采食量顯著高于對(duì)照組,AgRPmRNA表達(dá)水平亦顯著上調(diào);中樞注射 10μg劑量的 L-亮氨酸能強(qiáng)烈抑制采食,下丘腦 AgRPmRNA表達(dá)量顯著降低。Blouet等[4]研究也表明,在大鼠和小鼠下丘腦內(nèi)側(cè)基底部注射 L-亮氨酸均能顯著降低采食量、體增重以及動(dòng)物采食的頻率,并認(rèn)為此效應(yīng)是通過(guò)激活下丘腦內(nèi)側(cè)基底部的阿片 -促黑素細(xì)胞皮質(zhì)素原(POMC)神經(jīng)元、室旁核神經(jīng)元、孤束核飽感效應(yīng)器神經(jīng)元而實(shí)現(xiàn)的。

盡管腦室注射亮氨酸具有強(qiáng)烈的食欲調(diào)節(jié)作用,但飼糧中添加亮氨酸對(duì)哺乳動(dòng)物和禽類(lèi)的研究報(bào)道效應(yīng)并不明顯。López等[5]報(bào)道,飼糧中添加 L-亮氨酸對(duì)泌乳期大鼠的采食量、產(chǎn)熱量、體增重均無(wú)顯著影響,但是卻顯著抑制了下丘腦促食欲肽 NPY和 AgRPmRNA的表達(dá)。Y in等[6]運(yùn)用低蛋白質(zhì)飼糧飼喂 21日齡的斷奶仔豬,發(fā)現(xiàn)添加 0.27%和 0.55%的L-亮氨酸對(duì) 2周內(nèi)各組豬的采食量沒(méi)有明顯改變,但添加 0.55%的L-亮氨酸組的日增重分別比對(duì)照組和 0.27%組顯著提高61%和 41%。對(duì)禽類(lèi)的研究表明,在含有支鏈氨基酸纈氨酸(0.60%)和異亮氨酸(0.82%)的基礎(chǔ)飼糧中添加 5%的亮氨酸能減少雞的采食量和體增重,降低飼料利用效率。而當(dāng)纈氨酸和異亮氨酸含量分別增加至 0.80%和 1.07%時(shí),亮氨酸的抑制采食效應(yīng)消失[7]。

亮氨酸對(duì)采食的影響可能有 2方面的作用通路。一方面,亮氨酸是激活哺乳動(dòng)物雷帕霉素靶蛋白(mTOR)信號(hào)通路最有效的氨基酸[8]。由于mTOR是一種充當(dāng)代謝感受器的絲氨酸 /蘇氨酸蛋白激酶,它對(duì)氨基酸和生長(zhǎng)因子都非常敏感。因此,Cota等[2]和 Morrison等[3]都認(rèn)為亮氨酸可以直接激活下丘腦 mTOR信號(hào)通路發(fā)揮食欲調(diào)節(jié)活性。另一方面,肌肉氧化亮氨酸產(chǎn)物的 α-酮異己酸的能力在絕食時(shí)可提高 3～5倍,泌乳期大鼠乳腺中支鏈氨基酸轉(zhuǎn)氨酶活力和亮氨酸氧化率均上升[9]。亮氨酸轉(zhuǎn)氨基產(chǎn)物 α-酮異己酸通過(guò)促進(jìn)胰島素的分泌[10],抑制胰高血糖素分泌,從而抑制糖原異生,降低血糖濃度,從而間接參與食欲的調(diào)節(jié),這可能正是 López等[5]和 Yin等[6]給哺乳動(dòng)物(大鼠和仔豬)長(zhǎng)期飼喂 L-亮氨酸過(guò)程中亮氨酸并未表現(xiàn)出明顯的食欲抑制效應(yīng)的主要原因。

2 色氨酸對(duì)畜禽采食的調(diào)控作用

色氨酸是哺乳動(dòng)物的必需氨基酸和生糖氨基酸。飼養(yǎng)試驗(yàn)表明,色氨酸對(duì)動(dòng)物擇食以及采食量均有重要影響,仔豬會(huì)選擇性地采食高濃度色氨酸的飼糧[11]。Burgoon等[12]研究表明,給 6～16 kg仔豬飼喂低色氨酸(0.130%)的飼糧,其采食量比飼喂含足夠色氨酸(0.205%)的飼糧低40%。Eder等[13]也證實(shí),新生仔豬對(duì)色氨酸缺陷型飼糧的采食量明顯比對(duì)照組的少,甚至只有對(duì)照組的 38%～45%[14-15]。對(duì)母豬的研究也有類(lèi)似的趨勢(shì)[16]。此外,席鵬彬等[17]研究表明,與0.11%色氨酸缺乏組相比,0.14%～0.23%色氨酸添加組公、母雞的日采食量分別提高 4.5%～19.5%和 2.2% ～9.0%,下丘腦 5-羥色胺(5-HT)濃度分別提高 37.9%～83.6%和 7.3%～38.7%。

給嚙齒動(dòng)物和禽類(lèi)腹腔注射色氨酸均能夠顯著抑制采食。大鼠腹腔注射 100 mg/kg BW的色氨酸使 1、2、12 h的采食量分別減少 45%、33%、11%[18-19]。Lacy等[20]研究發(fā)現(xiàn),給自由采食的雞腹腔注射色氨酸能呈劑量依賴(lài)型地減少采食量,但是對(duì)禁食 24 h的雞沒(méi)有影響。對(duì)禁食 24 h的雞腦室注射 5-HT則抑制其采食[21]。

色氨酸不僅參與動(dòng)物機(jī)體蛋白質(zhì)的合成和代謝網(wǎng)絡(luò)調(diào)節(jié),也是 5-HT、褪黑激素、色胺、煙酰胺腺嘌呤二核苷酸(NAD)、煙酰胺腺嘌呤二核苷酸磷酸(NADP)和煙酸等的前體物,這些代謝產(chǎn)物對(duì)動(dòng)物的采食具有非常重要的影響。目前認(rèn)為,色氨酸對(duì)采食量的調(diào)控有生長(zhǎng)素(ghrelin)和 5-HT 2條相互獨(dú)立的途徑[22]。口服色氨酸可提高仔豬的采食量和血漿 ghrelin水平,并增加胃腸黏膜 ghrelin mRNA的表達(dá),而口服 5-HT則可降低仔豬的采食量,并且不影響血清中的 ghrelin水平。色氨酸發(fā)揮作用的另一個(gè)途徑被認(rèn)為和 5-HT有關(guān)[23]。大量研究表明,飼糧中增加色氨酸的量會(huì)增加采食量并伴隨著腦內(nèi) 5-HT的增加[24-25]。也有人認(rèn)為色氨酸缺乏會(huì)導(dǎo)致肉仔雞增重和采食抑制,原因可能是當(dāng)色氨酸嚴(yán)重缺乏時(shí),大腦中 5-HT耗竭,導(dǎo)致采食量急劇下降[26-27]。

3 組氨酸對(duì)采食調(diào)控的影響

組氨酸是堿性的半必需氨基酸,高組氨酸飼糧不利于動(dòng)物采食。Hitomi-Ohmura等[28]報(bào)道,大鼠飼糧添加 5%組氨酸,其采食量顯著降低。Kasaoka等[29]也發(fā)現(xiàn),大鼠飼糧添加 4.5%組氨酸能夠顯著降低采食量。另外,給大鼠飼喂 5%組氨酸飼糧,不僅能降低采食量,而且還可以減少采食的次數(shù)[30]。Goto等[31]大鼠采食高組氨酸飼糧,經(jīng)6 h后,抑制采食的效應(yīng)才達(dá)到顯著水平,此時(shí)的血液葡萄糖濃度也顯著升高。

外周及中樞注射組氨酸同樣能夠抑制哺乳動(dòng)物的采食量。Schwartz等[32]報(bào)道,大鼠腹腔注射組氨酸使腦內(nèi)組胺濃度升高。腦室注射組胺能廣泛抑制大鼠、貓和山羊的采食行為[33-35]。腦室注射組氨酸對(duì)大鼠采食產(chǎn)生明顯的抑制效應(yīng)[36]。Lecklin等[37]對(duì)大鼠腦室注射 100～800 nmol組氨酸,結(jié)果顯著降低大鼠的采食量。

現(xiàn)有研究表明,組氨酸可能主要通過(guò)合成組胺而發(fā)揮生物學(xué)功能。組胺能神經(jīng)元廣泛分布于腦內(nèi)各個(gè)區(qū)域,哺乳動(dòng)物的 3種組胺受體(H1、H2、H3)在腦內(nèi)絕大部分區(qū)域均有分布[38]。研究證明,下丘腦組胺通過(guò) H1受體調(diào)控動(dòng)物的采食行為[39-40]。組胺是由組氨酸合成所得,它能激活位于下丘腦的組胺能神經(jīng)元而抑制采食[41]。這種抑制采食的效應(yīng)可能是因?yàn)橄虑鹉X的組氨酸脫羧酶(HDC)催化組氨酸轉(zhuǎn)變?yōu)榻M胺而產(chǎn)生的。多項(xiàng)研究也支持以上結(jié)論,飼糧添加組氨酸抑制大鼠采食,作用機(jī)制可能就是激活了下丘腦的組胺能神經(jīng)元[29,42]。

4 谷氨酸對(duì)采食調(diào)控的影響

谷氨酸是哺乳動(dòng)物中樞神經(jīng)系統(tǒng)內(nèi)含量最高的興奮性氨基酸,它與快速興奮性突觸傳遞、中樞神經(jīng)系統(tǒng)發(fā)育調(diào)節(jié)等多種機(jī)能有關(guān)[43]。腦內(nèi)含有大量的谷氨酸,絕大部分都是在細(xì)胞內(nèi)尤其是神經(jīng)末梢。谷氨酸不僅是中樞系統(tǒng)內(nèi)的信號(hào)物質(zhì),還在外周器官和組織中充當(dāng)傳遞信號(hào)的角色[44-47]。谷氨酸需要通過(guò)其受體發(fā)揮傳遞信號(hào)作用,動(dòng)物禁食期間,內(nèi)源性的谷氨酸釋放于下丘腦外側(cè)區(qū),而采食期間谷氨酸釋放會(huì)迅速衰減[48]。

中樞注射谷氨酸對(duì)哺乳動(dòng)物和禽類(lèi)的采食調(diào)控效應(yīng)截然相反。Duva等[49-50]對(duì)飽食后的大鼠腦室注射谷氨酸或者谷氨酸受體激動(dòng)劑,發(fā)現(xiàn)大鼠會(huì)產(chǎn)生強(qiáng)烈但短暫的采食行為。但 Zeni等[51]用鴿子作為試驗(yàn)動(dòng)物模型的研究結(jié)果表明,禁食24 h的鴿子腦室注射谷氨酸,能夠呈劑量依賴(lài)型地減少采食量和采食持續(xù)的時(shí)間,但對(duì)自由采食的鴿子卻無(wú)此效應(yīng)。Zendehdel等[52]研究也發(fā)現(xiàn),3周齡肉雞禁食 24 h后,腦室注射 300和600μmol的谷氨酸,能夠劑量依賴(lài)性地減少雞的采食量。

5 其他氨基酸對(duì)采食調(diào)控的影響

除上述 4種氨基酸以外,目前關(guān)于其他氨基酸影響動(dòng)物采食調(diào)控的研究相對(duì)較少。Ng等[18]對(duì)大鼠腹腔注射 100 mg/kg體重的酪氨酸,發(fā)現(xiàn)分別顯著減少 1(37%)和 2 h(38%)的采食量。當(dāng)動(dòng)物適應(yīng)了賴(lài)氨酸缺乏型的飼糧后,極低濃度的賴(lài)氨酸改變都能明顯刺激動(dòng)物對(duì)飼糧的選擇以及采食量。賴(lài)氨酸缺陷型動(dòng)物會(huì)選擇相對(duì)含量較高的賴(lài)氨酸飼糧以盡量維持自身的生存狀態(tài)[53]。6日齡蛋雞中樞注射 8μmo l的 L-精氨酸顯著抑制其采食量[54]。此外,在斷奶仔豬飼糧添加過(guò)量的蛋氨酸(4%),試驗(yàn)期間仔豬采食量顯著降低[55]。Even等[56]研究表明,飼喂蘇氨酸缺乏型飼糧的大鼠的采食量明顯降低。Obeid等[57]在大鼠飼糧中添加谷氨酰胺,發(fā)現(xiàn)在為期 3周的試驗(yàn)期中,前 2周大鼠的采食量顯著高于對(duì)照組。

6 小 結(jié)

營(yíng)養(yǎng)素反饋調(diào)節(jié)動(dòng)物采食的機(jī)制比較復(fù)雜。深入認(rèn)識(shí)各種氨基酸對(duì)動(dòng)物采食的調(diào)控作用及其機(jī)制,對(duì)配制氨基酸平衡飼糧具有重要的參考價(jià)值。但目前某些氨基酸(如亮氨酸)對(duì)哺乳動(dòng)物和禽類(lèi)的采食調(diào)控作用剛好相反。即使對(duì)于同一物種,氨基酸通過(guò)飼喂、外周注射和中樞注射的效應(yīng)也不盡相同。盡管已有研究表明 m TOR通路、磷酸腺苷活化蛋白激酶(AMPK)通路等信號(hào)通路可能參與了氨基酸對(duì)攝食行為的調(diào)控,但目前仍不能完全解釋其詳細(xì)的作用機(jī)制,今后有必要在深入揭示畜禽采食調(diào)控的差異及其分子機(jī)制的基礎(chǔ)上,從更廣泛的作用途徑和信號(hào)通路去揭示氨基酸對(duì)畜禽采食的調(diào)控作用及其機(jī)制。

[1] BERTHOUD H R.Mu ltiple neural systems contro lling food intake and body weight[J].Neuroscience＆Biobehavioral Review s,2002,26：393-428.

[2] COTA D,PROULX K,SM ITH K A B,et al.Hypothalam ic m TOR signaling regu lates food intake[J].Science,2006,312：927-930.

[3] MORRISON C D,XIX,WHITEC L,etal.Am ino acids inhibit Agrp gene exp ression via an m TOR-dependentmechanism[J].American Journalof Physiology Endocrino logy and Metabolism,2007,293：165-171.

[4] BLOUET C,JO Y H,LIX,etal.Mediobasalhypothalam ic leucine sensing regu lates food intake through activation of a hypothalam us-brainstem circuit[J].The Journal of Neuroscience.2009,29(26)：8302-8311.

[5] LóPEZ N,SáNCHEZ J,PICóC,etal.D ietary L-leucine supp lementation o f lactating rats resu lts in a tendency to increase lean/fat ratio associated to lower orexigenic neuropep tide expression in hypothalamus[J].Peptides,2010,31：1361-1367.

[6] Y IN Y,YAO K,LIU Z,etal.Supp lementing L-leucine to a low-protein diet increases tissue protein synthesis in weanling pigs[J].Am ino Acids,2010,39：1477-1486.

[7] CALVERTC C,KLASING K C,AUSTIC R E.Invo lvement of food intake and am ino acid catabolism in the branched-chain am ino acid antagonism in chicks[J].The Journal of Nutrition,1982,112：627-635.

[8] PROUD C G.m TOR-m ediated regulation of translation factors by am ino acids[J].Biochem ical and biophysical research communications,2004,313：429-436.

[9] ICHIHARA A,NODA C,OGAWA K.Control of leucinemetabolism with special reference to branched-chain am ino acid transam inase isozymes[J].Advances in Enzyme Regulation,1973,11：155-166.

[10] HOLZE S,PANTEN U.Studies on the role ofβ-cell metabo lism in the insulinotropic effect ofα-ketoisocaproic acid[J].Biochim ica et Biophysica Acta(BBA)-General Subjects,1979,588(2)：211-218.

[11] ETTLE T,ROTH F X.Specific dietary selection for tryp tophan by the piglet[J].Journal o f Animal Science,2004,82：1115-1121.

[12] BURGOON K G,KNABE D A,GREGG E J.Digestible tryptophan requirements of starting,grow ing,and finishing pigs[J].Journal of Animal Science,1992,70：2493-2500.

[13] EDER K,PEGANOVA S,KLUGE H.Studies on the tryptophan requirementof piglets[J].Archives o f Animal Nutrition,2001,55(4)：281-297.

[14] SCHUTTE JB,VANWEERDEN E J,KOCH F.U-tilization o f DL-and L-tryptophan in young pigs[J].Animal Production,1988,46：447-452.

[15] 林映才,蔣宗勇,余德謙,等.斷奶仔豬色氨酸需求參數(shù)的研究[J].動(dòng)物營(yíng)養(yǎng)學(xué)報(bào),1999,11(3)：44-50.

[16] LIBAL G W,UTTECHT D J,HAM ILTON C R.Tryptophan needs of lactating sow s fed diets supplemented w ith crystalline lysine[J].Journal of Animal Science,1997,75：417-422.

[17] 席鵬彬,林映才,蔣宗勇,等.飼糧色氨酸對(duì) 43～63日齡黃羽肉雞生長(zhǎng)胴體品質(zhì)、體成分沉積及下丘腦5-羥色胺的影響[J].動(dòng)物營(yíng)養(yǎng)學(xué)報(bào),2009,21(2)：137-145.

[18] NG L T,ANDERSON G H.Route of adm inistration of tryptophan and tyrosine affects short-term food intake and plasma and brain am ino acid concentrations in rats[J].Journal of Nutrition,1992,122(2)：283-293.

[19] CO爦KUN爦, ?ZER?,G?NüL B,et al.The effect of repeated tryptophan adm inistration on body weight,food intake,brain lipid peroxidation and serotonin immunoreactivity in m ice[J].Molecular and Cellular Biochem istry,2006,286(1/2)：133-138.

[20] LACY M P,VAN KREY H P,SKEWES P A,et al.Intraperitoneal in jections o f tryptophan inhibit food intake in the fow l[J].Pou ltry Science,1986,65(4)：786-788.

[21] LACY M P,VAN KREY H P,SKEW ES P A,et al.Food intake response of genetically selected high and low-w eight line cockerels to p lasma infusions from fasted fow l[J].Poultry Science,1987,66：1224-1228.

[22] ZHANG H W,YIN JD,LID F,et al.Tryp tophan enhances ghrelin expression and secretion associated w ith increased food intake and w eight gain in w eanling pigs[J].Domestic Animal Endocrinology,2007,33：47-61.

[23] PEISKER M,SIMM INS P H.Tryptophan as feed intake stimulant[J].Feed M ix,1998,6：8-12.

[24] MEUN IER-SALAUN M C,MONNIER M,COLLEAUX Y,et al.Impact of dietary tryptophan and behavioral typeon behavior,plasma cortisol,and brainm etabo lites of young pigs[J].Journal o f Animal Science,1991,69：3689-3698.

[25] HENRY Y,SEVE B.Feed intake and dietary am ino acid balance in grow ing pigs w ith special reference to lysine,tryptophan and threonine[J].Pig New s and Information,1993,14：35-43.

[26] 喻兵權(quán),商振宇,程鵬,等.不同色氨酸水平對(duì)生長(zhǎng)育成肉雞生長(zhǎng)性能和胴體品質(zhì)的影響[J].畜禽業(yè),2007,10：10-13.

[27] ANDREW A F,FRANK H,MARKUSR.Estimates of individual factors of the tryptophan requirements based on protein and tryptophan accretion responses to increasing tryptophan supp ly in broiler chickens 8-21 days of age[J].A rchives of Animal Nutrition,2005,59(3)：181-190.

[28] H ITOM I-OHMURA E,AMANO N,AOYAMA Y,et al.The effect of a histidine-excess diet on cholestero l synthesis and degradation in rats[J].Lipids,1992,27：755-760.

[29] KASAOKA S,KAWAHARA Y,INOUE S,et al.Gender effects in dietary histidine-induced anorexia[J].Nutrition,2005,21：855-858.

[30] BASSIL M S,HWALLA N,OMAR A,et al.Meal pattern of male rats maintained on histidine-,leucine-,or tyrosine-supplemented diet[J].Obesity,2007,15：616-623.

[31] GOTO K,KASAOKA S,TAK IZAWA M,et al.Bitter taste and blood glucose are not invo lved in the suppressive effect of dietary histidine on food intake[J].Neuroscience Letters,2007,420：106-109.

[32] SCHWARTZ J C,LAMPART C,ROSE C.H istam ine formation in ratbrain in vivo：effects of histidine loads[J].The Journal of Neurochem istry,1972,19：801-810.

[33] MACH IDORIH,SAKATA T,YOSH IMATSU H,et al.Zucker obese rats：defect in brain histam ine control on feeding[J].Brain Research,1992,590：180-186.

[34] CLINESCHM IDT B V,LOTTI V J.H istam ine：intraventricu lar in jection supp resses ingestivebehavioro f the cat[J].A rchives Internationales de Pharmacodynam ie etde Therapie,1973,206：288-298.

[35] TUOM ISTO L,ERIKSSON L.Antidiuresis induced by in fusions of histam ine into the brain ventricles o f conscious goats[J].European Journal of Pharmacology,1979,54：191-201.

[36] ORTHEN-GAMBILL N.Antihistam inic d rugs increase feeding,w hile histidine suppresses feeding in rats[J].Pharmacology Biochem istry and Behavior,1988,31：81-86.

[37] LECKLIN A,ETU-SEPP?L? P,STARK H,et al.Effects of intracerebroventricu larly infused histam ine and selective H1,H2and H3agonists on food and water intake and urine flow in Wistar rats[J].Brain Research,1998,793：279-288.

[38] SCHWARTZJM,ARRANG JM,GARBARG M,et al.Histam inergic transm ission in the mammalian brain[J].Physiological Reviews,1991,71：1-51.

[39] SAKATA T,OOKUMA K,FUKAGAWA K,et al.Blockade o f the histam ine H1-recep tor in the rat ventromedial hypothalamus and feeding elicitation[J].Brain Research,1988,441：403-407.

[40] FUKAGAWA K,SAKATA T,SHIRA ISHIT,et al.Neuronal histam ine m odulates feeding behavior through H1-receptor in rat hypothalamus[J].American Journalof Physiology,1989,256：R 605-R 611.

[41] SAKATA T,YOSH IMATSU H,KUROKAWA M.Hypothalam ic neuronal histam ine：imp lication of its hom eostatic controlof energy metabolism[J].Nutrition,1997,13：403-411.

[42] KASAOKA S,TSUBOYAMA-KASAOKA N,KAWAHARA Y,et al.H istidine supplementation supp resses food intake and fat accumulationin rats[J].Nutrition,2004,20：991-996.

[43] FONNUM F.Glutamate：a neurotransm itter in mammalian brain[J].Journal of Neurochem istry,1984,42：1-11.

[44] SCHOUSBOE A.Transport and metabolism of glutamate and GABA in neurons and glial cells[J].International Review of Neurobiology,1981,22：1-45.

[45] HAMBERGER A,BERTHOLD CH,KARLSSON B,et al.ExtracellularGABA,glutamate and g lutam ine in vivo-perfusion-dialysis of rabbit hippocampus[J].Neuro l Neurobiol,1983,7：473-492.

[46] OTTERSEN O P,ZHANG N,WALBERG F.M etabolic compartmentation of glutamate and glutam ine：morphological evidence obtained by quantitative immunocytochem istry in rat cerebellum[J].Neuroscience,1992,46：519-534.

[47] MORIYAMA Y,HAYASHIM,YAMADA H,etal.Synaptic-like m icrovesicles,synaptic vesicle counterparts in endocrine cells,are involved in a novel regulatorymechanism for the synthesis and secretion of hormones[J].The Journal o f Experimental Biology,2000,203：117-125.

[48] RADA P,TUCCI S,MURZI E,et al.Extracellular glutamate increases in the lateral hypothalamus and decreases in the nucleus accumbens during feeding[J].Brain Research,1997,768：338-340.

[49] DUVA M A,TOMK INS E M,MORANDA L M,et al.Reverse microdialysis of N-methyl-D-aspartic acid into the lateral hypothalamus of rats：effects on eating and other behaviors[J].Brain Research,2001,921：122-132.

[50] DUVA M A,TOMK INS E M,MORANDA L M,et al.Regional differences in feeding and other behaviors elicited by N-methyl-D-aspartic acid in the rodent hypothalamus：a reverse m icrodialysis mapping study[J].Brain Research,2002,925：141-147.

[51] ZENIL A Z R,SEIDLER H B K,DE CARVALHO N A S,et al.Glutamatergic control of food intake in pigeons：evects of central injections o f g lutamate,NMDA,and AMPA receptor agonists and antagonists[J].Pharmacology Biochem istry and Behavior,2000,65(1)：67-74.

[52] ZENDEHDELM,BAGHBANZADEH A,BABAPOUR V,et al.The effects of bicucu lline and muscimol on glutamate-induced feeding behavior in broiler cockerels[J].Journal of Comparative Physio logy A,2009,195：715-720.

[53] HRUPKA B J,LIN Y,GIETZEN DW,et al.Lysine deficiency alters diet selection without dep ressing food intake in rats[J].Nutritional Neurosciences,1999,129：424-430.

[54] KHAN M S I,TACH IBANA T,HASEBE Y,et al.Peripheralor central adm inistration of nitric oxide synthase inhibitor affects feeding behavior in chicks[J].Comparative Biochem istry and Physiology-Part A,2007,148：458-462.

[55] EDMONDSM S,GONYOU HW,DAVID H,et al.Effect of excess levels o fmethionine,tryptophan,arginine,lysine or threonine on grow th and dietary choice in the pig[J].Journal of Animal,1987,65：179-185.

[56] EVEN P C,ROLLAND V,FEURTE S,et al.Postprandialmetabolism and aversive response in rats fed a threonine-devoid diet[J].American Journal of Physiology Regulatory Integrative Comparative Physiology.2000,279：248-254.

[57] OBEID O A,JAMAL ZM,HWALLA N,etal.The effect of glutam ine and dihydroxyacetone supplementation on food intake,weight gain,and postp randial glycogen synthesis in female Zucker rats[J].Nutrition,2006,22：794-801.