門小明　陶　新　徐子偉

(浙江省農(nóng)業(yè)科學(xué)院畜牧獸醫(yī)研究所，杭州310021)

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鳶尾素-前體基因：分子結(jié)構(gòu)、表達(dá)調(diào)控和生物學(xué)功能及其與骨骼肌纖維類型轉(zhuǎn)化

門小明陶新徐子偉*

(浙江省農(nóng)業(yè)科學(xué)院畜牧獸醫(yī)研究所，杭州310021)

摘要：鳶尾素(irisin)是新近發(fā)現(xiàn)的可分泌型肌源細(xì)胞因子，來源于Ⅲ型纖連蛋白組件包含蛋白5水解形成的多肽片段。目前證明鳶尾素及其前體基因在糖脂代謝疾病發(fā)生與運(yùn)動(dòng)治療中發(fā)揮作用，可能與骨骼肌纖維類型轉(zhuǎn)化存在關(guān)聯(lián)。本文通過總結(jié)鳶尾素及其前體基因分子結(jié)構(gòu)特點(diǎn)、表達(dá)調(diào)控和生物學(xué)功能最新研究進(jìn)展，結(jié)合骨骼肌纖維類型轉(zhuǎn)化機(jī)制，探討分析鳶尾素-前體基因途徑與骨骼肌纖維類型轉(zhuǎn)化潛在分子關(guān)聯(lián)，以期為畜禽肉質(zhì)改良提供新思路。

關(guān)鍵詞：鳶尾素；前體基因；過氧化物酶體增殖物激活受體γ輔激活因子；肉質(zhì)性狀

骨骼肌纖維類型組成是影響畜禽肉質(zhì)性狀重要因素。肌纖維類型特征表現(xiàn)復(fù)雜且活體不易測(cè)定，分子水平尋找有效遺傳選擇標(biāo)記和營(yíng)養(yǎng)調(diào)控靶點(diǎn)成為領(lǐng)域研究重點(diǎn)。甲狀腺素、胰島素樣生長(zhǎng)因子、鈣離子信號(hào)通路、Wnt信號(hào)通路、腺苷酸活化蛋白激酶(AMPK)、過氧化物酶體增殖激活受體(PPARs)及過氧化物酶體增殖激活受體γ輔助激活因子(PGC-1α)等先后被證明參與骨骼肌纖維類型轉(zhuǎn)化，大部分信號(hào)通路或因子在多種組織存在且作用廣泛，缺乏與骨骼肌纖維類型轉(zhuǎn)化特異性關(guān)聯(lián)。新近發(fā)現(xiàn)的可分泌型肌源細(xì)胞因子——鳶尾素(irisin)，參與機(jī)體肥胖及胰島素抗性等代謝疾病運(yùn)動(dòng)的治療過程，其表達(dá)具有PGC-1α依賴和運(yùn)動(dòng)誘導(dǎo)性，并且血清鳶尾素水平與其生理功能呈正相關(guān)[1]，這為骨骼肌纖維類型遺傳標(biāo)記和營(yíng)養(yǎng)調(diào)控研究提供了思路。本文將對(duì)鳶尾素-Ⅲ型纖連蛋白組件包含蛋白5(fibronectin type Ⅲ domain-containing protein 5,FNDC5)途徑研究最新進(jìn)展及其與骨骼肌纖維類型轉(zhuǎn)化分子關(guān)聯(lián)作以綜述介紹。

1鳶尾素-前體基因分子結(jié)構(gòu)、表達(dá)調(diào)控和生物學(xué)功能

1.1分子結(jié)構(gòu)特點(diǎn)

鳶尾素是Bostr?m等[1]在骨骼肌中發(fā)現(xiàn)的一種分泌型糖基化蛋白，由112個(gè)氨基酸構(gòu)成，分子質(zhì)量為12 ku。鳶尾素來源于前體蛋白FNDC5，又被稱作Ⅲ型纖連蛋白重復(fù)包含蛋白2或過氧化物酶體蛋白[2-3]。

如圖1所示，F(xiàn)NDC5蛋白分子由信號(hào)肽(29個(gè)氨基酸)、Ⅲ型纖連蛋白組件(112個(gè)氨基酸)和C-端跨膜結(jié)構(gòu)域(65個(gè)氨基酸)3部分構(gòu)成，分子質(zhì)量約32 ku[5]，經(jīng)蛋白酶水解剪切后形成分泌型FNDC5多肽片段即鳶尾素分子，進(jìn)入血液循環(huán)系統(tǒng)。鳶尾素剪切釋放過程與表皮生長(zhǎng)因子(EGF)、轉(zhuǎn)移生長(zhǎng)因子(TGF)的剪切形成具有高度相似性[5]。Teufel等[3]研究發(fā)現(xiàn)，F(xiàn)NDC5編碼基因位于第4號(hào)染色體上，長(zhǎng)度約為5.1 kb，包含6個(gè)外顯子；第1個(gè)外顯子包含轉(zhuǎn)錄起始區(qū)，第1、2個(gè)外顯子共同表達(dá)信號(hào)肽，第2、3個(gè)外顯子共同表達(dá)Ⅲ型纖連蛋白組件，第4、5個(gè)外顯子表達(dá)跨膜結(jié)構(gòu)域。FNDC5蛋白及鳶尾素分子在不同物種間具有高度保守性[6]，如在人類和嚙齒類動(dòng)物相似度達(dá)到100%，高于胰島素、胰高血糖素及瘦素的85%、90%和83%相似度。這種高度保守性為目前鳶尾素-FNDC5基因進(jìn)展用于畜禽肉質(zhì)調(diào)控研究提供了參考基礎(chǔ)。

圖1　FNDC5蛋白氨基酸序列與構(gòu)成

1.2表達(dá)及其調(diào)控

FNDC5基因表達(dá)和鳶尾素分泌最先在人、兔及小鼠骨骼肌和血清中被檢測(cè)發(fā)現(xiàn)[7]。Huh等[6]利用熒光定量PCR檢測(cè)發(fā)現(xiàn)，F(xiàn)NDC5 mRNA主要在骨骼肌、心臟、舌和直腸等富含肌肉組織器官，以及視神經(jīng)和腦組織中表達(dá)，在腎臟、肝臟及肺臟少量表達(dá)，鳶尾素分子還在皮膚真皮層及皮下組織檢測(cè)發(fā)現(xiàn)[8]，肌肉組織生長(zhǎng)發(fā)育程度直接影響血液鳶尾素水平。有研究發(fā)現(xiàn)，F(xiàn)NDC5 mRNA和鳶尾素在嚙齒類和人的脂肪組織中大量表達(dá)存在，也被稱之為脂肪細(xì)胞因子[9-10]。鳶尾素分子還在人類腦脊液、母乳及唾液中被發(fā)現(xiàn)[11-13]，這為相關(guān)研究提供了更廣闊的檢測(cè)空間。

鳶尾素-FNDC5基因表達(dá)調(diào)控具有明顯運(yùn)動(dòng)誘導(dǎo)和PGC-1α依賴性。Bostr?m等[1]通過特異性剔除小鼠肌肉組織PGC-1α基因，使血清鳶尾素含量減少72%，自由跑步運(yùn)動(dòng)3周后增加65%。正如Hofmann等[7]報(bào)道，不同運(yùn)動(dòng)類型及受試個(gè)體差異對(duì)鳶尾素-FNDC5基因表達(dá)產(chǎn)生重要影響。在正常人中，F(xiàn)NDC5基因表達(dá)僅在老年人能夠被耐力訓(xùn)練誘導(dǎo)增加，在年輕人或劇烈運(yùn)動(dòng)和高強(qiáng)度對(duì)抗訓(xùn)練者中都沒有應(yīng)答[14]；在心臟收縮性衰竭患者中，F(xiàn)NDC5 mRNA表達(dá)能夠被有氧運(yùn)動(dòng)誘導(dǎo)增加[15]；對(duì)肥胖兒童個(gè)體進(jìn)行為期1年的生活方式干預(yù)治療，使血液鳶尾素水平升高12%[16]。有氧運(yùn)動(dòng)后能夠使非肥胖糖尿病男性患者血清鳶尾素水平升高至2倍[17]，肥胖個(gè)體血清鳶尾素水平增加更高[13]，在青年小鼠也證明血清鳶尾素水平顯著升高[18]。也有不同研究結(jié)果發(fā)現(xiàn)，Lee等[19]和Kurdiova等[20]利用人原代骨骼肌細(xì)胞模擬運(yùn)動(dòng)治療，PGC-1αmRNA水平被升高2倍，F(xiàn)NDC5 mRNA卻降低18%，培養(yǎng)液鳶尾素濃度降低20%；每周3次持續(xù)26周運(yùn)動(dòng)訓(xùn)練并沒有改變志愿者血清鳶尾素水平。Hee等[21]研究指出，血清鳶尾素水平與受試者膳食結(jié)構(gòu)無顯著相關(guān)性，主要受運(yùn)動(dòng)類型影響。運(yùn)動(dòng)誘導(dǎo)哺乳動(dòng)物鳶尾素分泌很可能是從寒顫性肌肉收縮進(jìn)化而來，與棕色脂肪產(chǎn)熱相似[22]，但相關(guān)調(diào)控機(jī)理還有待證實(shí)。

1.3生物學(xué)功能

鳶尾素-FNDC5參與機(jī)體產(chǎn)熱、脂肪轉(zhuǎn)化及肥胖發(fā)生等過程。Bostr?m等[1]給正常飲食和高脂誘導(dǎo)肥胖小鼠靜脈注射FNDC5全長(zhǎng)腺病毒發(fā)現(xiàn)：正常飲食小鼠皮下脂肪組織的FNDC5 mRNA水平增加15倍，鳶尾素全血水平增加3～4倍，注射10 d后可檢測(cè)到解偶聯(lián)蛋白1(uncoupling protein 1,UCP1) mRNA水平增加13倍，細(xì)胞凋亡誘導(dǎo)因子(cell death-inducing Dff45 like effector,Cidea)表達(dá)顯著增加；肥胖小鼠皮下脂肪組織表現(xiàn)相似的棕色化模型，Cidea表達(dá)升高3倍，伴隨著耗氧量增加、體重減輕、糖耐量改善、空腹胰島素水平降低。Cidea主要在成年小鼠棕色脂肪組織表達(dá)，能夠調(diào)節(jié)機(jī)體脂類代謝與肥胖發(fā)生[22]。Bostr?m等[1]還發(fā)現(xiàn)，20 nmol/L的FNDC5蛋白可使UCP1 mRNA表達(dá)水平升高7～1 500倍，導(dǎo)致ATP合成受阻，產(chǎn)熱增加，消耗更多機(jī)體能量貯備即脂肪。

血清鳶尾素水平與肥胖、糖尿病等代謝疾病發(fā)生存在相關(guān)性。肥胖患者血清鳶尾素水平與體重指數(shù)、血糖水平等呈正相關(guān)，與年齡、胰島素、膽固醇等指標(biāo)呈負(fù)相關(guān)[6]；Ⅱ型糖尿病患者血清鳶尾素水平較低，與新發(fā)Ⅱ型糖尿病發(fā)病率呈負(fù)相關(guān)[23-24]；非酒精性脂肪肝肥胖患者血清鳶尾素水平相對(duì)較低，伴隨肝內(nèi)三酰甘油水平升高而逐漸減少，與血清谷丙轉(zhuǎn)氨酶及谷草轉(zhuǎn)氨酶的活性呈負(fù)相關(guān)[25]。與普通豬比較，高膽固醇血癥家族豬的肌肉和脂肪組織FNDC5基因mRNA表達(dá)水平?jīng)]有差異，但鳶尾素水平顯著升高[26]。與正常胎兒相比，宮內(nèi)遲緩發(fā)育胎兒臍帶血鳶尾素表達(dá)降低，大型胎兒鳶尾素表達(dá)水平?jīng)]有顯著變化；血清鳶尾素水平與胎兒初生體重呈正相關(guān)，在正常和大型胎兒組與胰島素水平呈正相關(guān)[27-28]。這可能與個(gè)體生長(zhǎng)后期代謝疾病發(fā)生存在某種關(guān)聯(lián)。一方面，鳶尾素水平降低將導(dǎo)致新生兒寒顫性產(chǎn)熱較少，脂肪組織代償性沉積加強(qiáng)，從而增加代謝疾病發(fā)生風(fēng)險(xiǎn)；相反，鳶尾素水平提高通過增加寒顫性產(chǎn)熱而降低脂肪沉積，從而減少代謝疾病發(fā)生可能。

此外，鳶尾素還與機(jī)體氧化應(yīng)激、甲狀腺功能紊亂、肌肉損傷、心血管疾病及癌癥發(fā)生等有關(guān)[29]。通過外源補(bǔ)充鳶尾素可以降低相關(guān)疾病損傷，如：重組鳶尾素可以抑制非酒精性脂肪肝細(xì)胞的精氨酸甲基轉(zhuǎn)移酶-3活性，進(jìn)而減少細(xì)胞氧化應(yīng)激、降低脂類合成與積累[30]；腹腔注射鳶尾素可以抑制高脂膳食Ⅱ型糖尿病小鼠的蛋白激酶C-β(PKC-β)/還原型煙酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶活性、核轉(zhuǎn)錄因子-κB(NF-κB)/誘導(dǎo)型一氧化氮合酶(iNOS)信號(hào)通路及過氧化亞硝基陰離子形成，從而改善血管內(nèi)皮細(xì)胞功能[31]。另有研究發(fā)現(xiàn)，通過給不運(yùn)動(dòng)小鼠注射FNDC5蛋白，可以激活腦源性神經(jīng)因子表達(dá)，促進(jìn)學(xué)習(xí)和記憶神經(jīng)元生長(zhǎng)，展現(xiàn)出在治療老年認(rèn)知減退、阿爾茨海默病以及帕金森綜合癥等神經(jīng)退行性疾病方面的潛在作用[32]。目前報(bào)道顯示，鳶尾素可能通過p38分裂原激活的蛋白激酶(MAPK)、細(xì)胞外信號(hào)調(diào)節(jié)激酶(ERK)-MAPK及PPARα等信號(hào)通路發(fā)揮作用[33-34]。隨著鳶尾素-FNDC5基因表達(dá)、分泌在更多組織被發(fā)現(xiàn)，將有更多鳶尾素-FNDC5生物學(xué)功能及作用機(jī)制被研究證實(shí)。

2骨骼肌纖維類型轉(zhuǎn)化機(jī)制

根據(jù)酶組化學(xué)反應(yīng)特性(三磷酸腺苷酶結(jié)合琥珀酸脫氫酶)或肌球蛋白重鏈(MyHC)亞基種類(Ⅰ、Ⅱa、Ⅱb和Ⅱx型)組成差異，動(dòng)物骨骼肌纖維被劃分成不同類型，在成年哺乳動(dòng)物包括快速氧化、慢速氧化、中間型和快速酵解4種不同類型[35]。不同類型肌纖維可以通過細(xì)胞內(nèi)外多種信號(hào)通路相互轉(zhuǎn)化，如經(jīng)典的鈣離子(Ca2+)信號(hào)通路。在神經(jīng)沖動(dòng)和激素誘導(dǎo)等細(xì)胞外信號(hào)刺激下，細(xì)胞內(nèi)Ca2+或鈣調(diào)素(CAMK)濃度升高；鈣調(diào)神經(jīng)磷酸酶(CaN)被激活，使活化T細(xì)胞核因子(NFATs)發(fā)生去磷酸化作用；去磷酸化NFATs進(jìn)入細(xì)胞核，與肌細(xì)胞增強(qiáng)子結(jié)合因子2(MEF2)、生肌決定因子(MyoD)及PGC-1α等核轉(zhuǎn)錄因子相互作用[36]，參與骨骼肌纖維類型轉(zhuǎn)化過程。

NFATs包含NFATc1等5個(gè)蛋白家族成員[37]，一方面可以選擇性激活慢肌纖維相關(guān)基因表達(dá)[38]；另一方面通過破壞MyoD與輔助轉(zhuǎn)錄激活因子p300的結(jié)合，抑制MyoD依賴性快肌纖維相關(guān)基因啟動(dòng)子活性，導(dǎo)致快肌纖維類型比例降低[39]。去磷酸化NFATs與核轉(zhuǎn)錄因子激活蛋白1(AP1)、MEF2及轉(zhuǎn)錄因子GATA2/4結(jié)合共同激活基因轉(zhuǎn)錄，經(jīng)糖原合成酶激酶-3β(GSK3-β)、蛋白激酶A(PKA)、促分裂原活化蛋白激酶(p38-MAP)和酪蛋白激酶等磷酸化作用后返回細(xì)胞質(zhì)，停止轉(zhuǎn)錄激活[40]。IGF-1通過增強(qiáng)NFATc1和GATA2活性刺激骨骼肌肥大增生，強(qiáng)直運(yùn)動(dòng)神經(jīng)通過增加NFATs與MEF2結(jié)合活性促進(jìn)慢速氧化型肌纖維形成[35]。

MEF2是一類轉(zhuǎn)錄因子，可以激活肌肉組織中富含A/T順式調(diào)節(jié)元件的特異性基因表達(dá)[41]，并在p38MAP和Ca2+/CaMK/CaN介導(dǎo)的肌肉細(xì)胞終末分化中發(fā)揮作用。同NFATc1一樣，MEF2可以與MyoD家族成員結(jié)合形成復(fù)合體，抑制MyoD依賴性快肌纖維基因表達(dá)[42]。叉形頭轉(zhuǎn)錄因子(FoxO)是胰島素/蛋白激酶B(Akt)信號(hào)通路的下游調(diào)控基因，被Akt磷酸化后失去結(jié)合目的基因活性[43]。人源FoxO1超表達(dá)轉(zhuǎn)基因小鼠骨骼肌組織塊有所減少，肌肉顏色較白，Ⅰ型肌纖維表達(dá)顯著降低，但Ⅱ型纖維表達(dá)未發(fā)生變化[44]；FoxO1在比目魚肌(Ⅰ型肌纖維為主)中表達(dá)豐度較低，在趾長(zhǎng)伸肌(Ⅱ型肌纖維為主)中表達(dá)豐度較高[45]；運(yùn)用RNAi技術(shù)抑制成肌細(xì)胞內(nèi)FoxO1表達(dá)，可使MEF2、CaMKⅡ、NFATs和MyoD等肌纖維類型相關(guān)基因上調(diào)表達(dá)[46]。因此FoxO1可能通過抑制MEF2、CaMK和NFATs等相關(guān)途徑降低Ⅰ型肌纖維含量。

圖2　PGC-1α與骨骼肌纖維類型轉(zhuǎn)化信號(hào)通路基因的分子關(guān)聯(lián)

如圖2所示，PGC-1α基因啟動(dòng)子存在MEF2、FoxO1和環(huán)磷酸腺苷反應(yīng)序列(CRE)結(jié)合區(qū)，其表達(dá)受胰島素-Akt-FoxO1、細(xì)胞因子運(yùn)動(dòng)-p38MAPK-MEF2ATF2、運(yùn)動(dòng)-CaNCaMKⅣ-MEF2環(huán)磷腺苷效應(yīng)元件結(jié)合蛋白(CREB)、寒冷刺激-β3腎上腺素受體(β3-AR)-PKA-CREB、胰高血糖素-GLGNR-PKA-CREB等信號(hào)通路調(diào)控[47]。通過PGC-1α轉(zhuǎn)基因小鼠研究證明，超表達(dá)PGC-1α可以促進(jìn)骨骼?、裥秃廷騛型纖維比例增加[48]，MyHCⅠ和Ⅱa mRNA表達(dá)增加、MyHCⅡb和Ⅱx mRNA表達(dá)降低[49]；敲除PGC-1α基因可以降低Ⅰ型肌纖維氧化呼吸作用、線粒體數(shù)量、耐力訓(xùn)練和抗疲勞能力[50]。顯然，PGC-1α成為調(diào)控骨骼肌纖維類型轉(zhuǎn)化(特別是氧化型纖維形成)的關(guān)鍵因子。

3鳶尾素-前體基因與骨骼肌纖維類型轉(zhuǎn)化的潛在關(guān)聯(lián)

PGC-1α是鳶尾素途徑與骨骼肌纖維類型轉(zhuǎn)化的主要關(guān)聯(lián)分子。PGC-1α在骨骼肌代謝調(diào)節(jié)中具有非常廣泛的生物學(xué)作用，如：糖原合成、脂肪酸轉(zhuǎn)運(yùn)與氧化、線粒體合成與修復(fù)、葡萄糖攝取、脂類合成、細(xì)胞自噬、增生性細(xì)胞因子分泌、肌纖維類型轉(zhuǎn)化、神經(jīng)肌肉接頭基因表達(dá)誘導(dǎo)、肌源因子分泌、促炎細(xì)胞因子分泌等，主要生理功能表現(xiàn)為促進(jìn)血管生成、提高氧化代謝能力、改善運(yùn)動(dòng)功能、緩解肌肉萎縮和營(yíng)養(yǎng)不良及調(diào)節(jié)胰島素敏感性，可以改善衰老性肌肉減少癥、線粒體功能缺乏及系統(tǒng)性炎癥等[51]，已成為相關(guān)代謝疾病治療的重要靶點(diǎn)，也是理解PGC-1α關(guān)聯(lián)骨骼肌纖維類型與鳶尾素-FNDC5途徑的重要基礎(chǔ)。

如圖3所示，有氧運(yùn)動(dòng)首先通過AMPK途徑刺激PGC-1α表達(dá)，后者一方面促進(jìn)FNDC5基因表達(dá)和鳶尾素分泌[52]，另一方面參與骨骼肌纖維類型轉(zhuǎn)化等代謝調(diào)節(jié)作用。同時(shí)，運(yùn)動(dòng)訓(xùn)練也是改變肌肉纖維類型組成的外界因素。如：耐力訓(xùn)練、拉伸和機(jī)械負(fù)荷等能夠增加肌肉非酵解型纖維比例，減少酵解型纖維比例[53-54]；戶外散養(yǎng)、寒冷環(huán)境能夠增加豬肌肉氧化型纖維比例，降低酵解型纖維比例[55]，與骨骼肌寒顫性收縮運(yùn)動(dòng)有關(guān)。此外，線粒體增多是氧化型肌纖維形成的重要標(biāo)志，也是鳶尾素作用的顯著結(jié)果。這些研究提示，鳶尾素-FNDC5途徑可能與氧化型肌纖維形成存在關(guān)聯(lián)，一方面受共同上游基因PGC-1α調(diào)控，另一方面鳶尾素也可能直接參與了骨骼肌纖維類型特征形成，有待深入研究。

圖3　PGC-1α成為鳶尾素-FNDC5途徑與骨骼肌纖維類型轉(zhuǎn)化的關(guān)聯(lián)分子

4鳶尾素-前體基因在畜禽肉質(zhì)調(diào)控中可能作用

不同纖維類型組成肌肉，通過宰后糖原酵解與磷酸肌酸轉(zhuǎn)化(ATP-CP)能力差異影響pH下降和白肌肉(PSE肉)形成，通過脂類氧化代謝差異影響肌內(nèi)脂肪沉積，通過細(xì)胞骨架及間質(zhì)形成、抗氧化狀態(tài)、線粒體ATP生成等進(jìn)一步影響肉質(zhì)性狀[56]，顯示出在畜禽肉質(zhì)調(diào)控中重要性。

由于鳶尾素及其前體基因具有糖脂代謝調(diào)節(jié)功能，且與骨骼肌纖維類型轉(zhuǎn)化相互關(guān)聯(lián)，也必將在肉質(zhì)形成與調(diào)控中發(fā)揮作用。一方面，可能成為骨骼肌纖維類型組成或肉質(zhì)性狀的重要分子標(biāo)記，如：FNDC5基因多態(tài)性、血清鳶尾素水平等。在人醫(yī)研究表明，F(xiàn)NDC5基因多態(tài)性與女性糖尿病患者血壓、脂類分布及血糖含量存在相關(guān)性[57-58]，血清鳶尾素水平存在人種差異[21]。另一方面，為肉質(zhì)營(yíng)養(yǎng)調(diào)控研究提供新依據(jù)。雖然鳶尾素-FNDC5基因特異性調(diào)控營(yíng)養(yǎng)素未見報(bào)道，由于FNDC5參與PGC-1α調(diào)控心肌分化和線粒體形成等過程[59]，PGC-1α天然配體或線粒體營(yíng)養(yǎng)素可直接提供相關(guān)參考。這些應(yīng)用研究還有待于鳶尾素-FNDC5基因在骨骼肌纖維類型及肉質(zhì)形成中作用機(jī)制證實(shí)。

5小結(jié)與展望

綜上所述，鳶尾素作為一種新發(fā)現(xiàn)肌源細(xì)胞因子，在抵抗肥胖和糖尿病治療等方面表現(xiàn)較高學(xué)術(shù)研究?jī)r(jià)值。鳶尾素-FNDC5表達(dá)調(diào)控及作用機(jī)制尚不清楚，如：調(diào)控鳶尾素-FNDC5表達(dá)分泌的細(xì)胞信號(hào)通路、FNDC5蛋白及鳶尾素作用靶點(diǎn)和功能效應(yīng)、影響鳶尾素水解分泌因素等問題，限制了在相關(guān)領(lǐng)域的進(jìn)一步應(yīng)用。目前鳶尾素的研究?jī)H限于試驗(yàn)動(dòng)物和人醫(yī)方面，在畜禽肉質(zhì)形成與改良中鮮有報(bào)道，深入研究鳶尾素-FNDC5途徑在骨骼肌纖維類型分化和代謝特征形成中的調(diào)控作用，必將為今后畜禽肉質(zhì)改良提供新的科學(xué)依據(jù)。

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(責(zé)任編輯武海龍)

Irisin-Processor Gene: Molecular Structure, Expressive Regulation,Biological Functions and the Associations with Skeletal Muscle Fiber Types

MEN XiaomingTAO XinXU Ziwei*

(Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Science, Hangzhou 310021, China)

Abstract:Irisin, as a novel myogenic factor, is produced by shear from fibronectin type Ⅲ domain containing protein 5 (FNDC5) and then secretes into blood circulation system. Irisin and its processor gene FNDC5 expression plays some roles on energy metabolism, obesity, diabetes and exercise therapy. This review summarized the recently research progresses about irisin and its processor gene FNDC5, majorly including their structure characteristics and physiological functions. Their molecular associations with skeletal muscle fiber types were discussed, combining the extracellular and intracellular signaling pathways mediating the conversion among different myofiber types. Our purpose was to provide some new ideas for improving pork quality through changing muscle fiber types.[Chinese Journal of Animal Nutrition, 2016, 28(2)：310-318]

Key words:irisin; processor gene; PGC-1α; meat quality

*Corresponding author, professor, E-mail: zjsnkyxzw@163.com

中圖分類號(hào)：S811.3

文獻(xiàn)標(biāo)識(shí)碼：A

文章編號(hào)：1006-267X(2016)02-0310-09

作者簡(jiǎn)介：門小明(1979—)，男，吉林扶余人，助理研究員，博士，主要從事動(dòng)物生產(chǎn)與品質(zhì)調(diào)控研究。E-mail：menxiaoming@126.com*通信作者：徐子偉，研究員，博士生導(dǎo)師，E-mail: zjsnkyxzw@163.com

基金項(xiàng)目：國(guó)家自然科學(xué)基金面上項(xiàng)目(31172220)；國(guó)家現(xiàn)代農(nóng)業(yè)產(chǎn)業(yè)技術(shù)研究體系(CARS-36)；浙江省科技廳資助項(xiàng)目

收稿日期：2015-09-09

doi：10.3969/j.issn.1006-267x.2016.02.002