張進威，羅毅，王宇豪，何劉軍，李明洲，王訊

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MicroRNA調(diào)控動物脂肪細胞分化研究進展

張進威，羅毅，王宇豪，何劉軍，李明洲，王訊

四川農(nóng)業(yè)大學(xué)動物科技學(xué)院，動物遺傳育種研究所，成都611130

脂肪組織不僅在維持機體能量代謝和穩(wěn)態(tài)上發(fā)揮重要作用，同時也是重要的內(nèi)分泌器官。脂肪細胞分化是由間充質(zhì)干細胞(Mesenchymal stem cells, MSC)向成熟脂肪細胞分化的復(fù)雜生理過程，該過程由大量轉(zhuǎn)錄因子、激素、信號通路分子協(xié)同調(diào)控。miRNA作為內(nèi)源性非編碼RNA，主要通過抑制轉(zhuǎn)錄后翻譯等機制來調(diào)控基因表達。近年來越來越多的證據(jù)表明miRNA通過調(diào)控脂肪細胞分化相關(guān)的轉(zhuǎn)錄因子和重要信號分子進而影響動物脂肪細胞的分化和脂肪形成。本文對miRNA影響動物白色、棕色和米色脂肪細胞分化的作用機制及其相關(guān)調(diào)控通路和關(guān)鍵因子進行了歸納總結(jié)，以期為肥胖等代謝性疾病的治療提供一定的理論指導(dǎo)和新的治療思路。

miRNA；白色脂肪細胞；棕色脂肪細胞；米色脂肪細胞；分化

肥胖是由能量攝入和代謝不平衡使得身體脂肪異常增多而引起的。隨著人們生活水平的提高和生活方式的改變，肥胖的比例正在逐年增加[1]。肥胖會導(dǎo)致一系列脂肪代謝紊亂引起的并發(fā)癥，如Ⅱ型糖尿病、高血壓、冠心病等[2]。脂肪組織在儲存能量、調(diào)節(jié)體溫、緩沖機械沖擊等方面具有非常重要的作用，當(dāng)糖代謝或脂代謝異常時，脂肪細胞體積增大(肥大)和數(shù)量增多(增生)，機體就會出現(xiàn)肥胖[3]。脂肪細胞有3種類型：白色脂肪細胞、棕色脂肪細胞和米色脂肪細胞。白色脂肪細胞的主要功能是以甘油三酯的形式儲存機體內(nèi)多余能量。棕色脂肪細胞胞質(zhì)中有許多線粒體，可以氧化脂類并以熱能的形式釋放。米色脂肪細胞是近年來新發(fā)現(xiàn)的一種脂肪細胞，在一定條件下由白色脂肪細胞轉(zhuǎn)化而來，并代謝產(chǎn)熱[4]。越來越多的研究表明，miRNA可以作為一種重要的調(diào)控因子參與調(diào)控脂肪細胞分化。隨著相關(guān)研究的不斷深入，miRNA調(diào)控脂肪細胞分化網(wǎng)絡(luò)正在逐步完善[5, 6]。本文基于miRNA的生物學(xué)功能，結(jié)合脂肪細胞分化過程，對近年來miRNA調(diào)控3種脂肪細胞分化的最新研究進展進行了綜述，為肥胖等代謝性疾病的治療提供一定的理論指導(dǎo)和新的治療思路。

1 miRNA的產(chǎn)生與生物學(xué)功能

miRNA是真核生物體內(nèi)廣泛存在的一類長度為19~22nt的單鏈非編碼RNA，在轉(zhuǎn)錄后水平調(diào)控靶基因表達，從而調(diào)控細胞增殖、分化、凋亡等多種生物學(xué)過程[7]。最早發(fā)現(xiàn)的miRNA是lin-4和let-7，它們可以調(diào)節(jié)秀麗隱桿線蟲()幼蟲階段性發(fā)育，從而拉開了miRNA研究的序幕[8]。經(jīng)典的miRNA產(chǎn)生途徑如下：miRNA基因在RNA聚合酶Ⅱ作用下轉(zhuǎn)錄形成幾百個核苷酸長度的初級轉(zhuǎn)錄物pri-miRNA；pri-miRNA在RNaseⅢ家族的Drosha酶和伴侶蛋白DGCR8組成的復(fù)合物作用下被加工成長度約60nt并具有莖環(huán)結(jié)構(gòu)的miRNA前體/pre-miRNA；pre-miRNA由轉(zhuǎn)運蛋白Exportin-5轉(zhuǎn)運到細胞質(zhì)，然后被RNaseⅢ家族的Dicer酶加工形成約20nt的雙鏈miRNA，最后解鏈形成成熟的單鏈miRNA[3, 9]。近年來在無脊椎動物和哺乳動物中發(fā)現(xiàn)了“mirtron途徑”，這一途徑不依賴Drosha酶而產(chǎn)生miRNA[10]。

在動物體內(nèi)，成熟的miRNA可以與特定的核糖核蛋白AGO(Argonaute)結(jié)合生成沉默復(fù)合體 (RNA-induced silencing complex, RISC)，RISC通過miRNA種子序列與mRNA 3′UTR或ORF區(qū)互補結(jié)合來識別靶基因，介導(dǎo)mRNA降解或抑制翻譯，從而調(diào)控靶基因表達[7, 8]。miRNA還可以與mRNA競爭結(jié)合RNA結(jié)合蛋白，從而調(diào)控mRNA表達，如在腫瘤中miR-29與RNA結(jié)合蛋白HuR(Human antigen R protein)結(jié)合，最終使未結(jié)合HuR的mRNA表達升高[11]。此外，有研究發(fā)現(xiàn)某些miRNA(如let-7、miR-125b[12])可以加速mRNA脫腺苷，降低細胞內(nèi)mRNA有效豐度，從而下調(diào)基因表達[13]。在某些植物中，miRNA可以介導(dǎo)自身基因座或靶基因甲基化，在表觀水平調(diào)控基因表達[14, 15]。一個miRNA可以調(diào)節(jié)多個靶基因，多個miRNA也能同時作用于一個基因，因此在機體內(nèi)就形成了復(fù)雜精細的miRNA調(diào)控網(wǎng)絡(luò)[8]。

2 脂肪細胞起源與分化的分子機制

哺乳動物有兩種脂肪組織：白色脂肪組織(White adipose tissue, WAT)和棕色脂肪組織(Brown adipose tissue, BAT)。WAT由大量白色脂肪細胞組成，成熟白色脂肪細胞含有一個大的脂滴，可以分泌一些脂肪細胞因子(如瘦素、脂聯(lián)素等)[16]。BAT中含有棕色脂肪細胞，經(jīng)典的棕色脂肪細胞中有許多小脂滴，胞質(zhì)中有許多線粒體，高表達解偶聯(lián)蛋白(Uncoupling protein-1, UCP-1)，UCP-1可以破壞線粒體內(nèi)膜兩側(cè)的跨膜質(zhì)子梯度，阻礙ATP形成，增加產(chǎn)熱。另外，米色脂肪細胞是近年來發(fā)現(xiàn)的新型脂肪細胞，它在一定條件下(長期冷刺激或β3-腎上腺素受體激動劑處理)由WAT中的白色脂肪細胞轉(zhuǎn)化而來[17]，通常米色脂肪細胞UCP-1表達較低，但經(jīng)米色化信號刺激后，胞內(nèi)UCP-1表達量顯著升高，從而發(fā)揮產(chǎn)熱功能[18, 19]。3種脂肪細胞均起源于間充質(zhì)干細胞(Mesenchymal stem cells, MSCs)，在不同調(diào)控元件共同作用下向每一種特定的細胞類型分化[16](圖1)。

圖1 3種脂肪細胞起源

MSC：間充質(zhì)干細胞；MYF5：成肌因子5；BMP：骨形成蛋白；FGF21：成纖維細胞生長因子21；Irisin：鳶尾素；Myogenin：肌細胞生成素；MyoD：肌分化因子。

2.1 白色脂肪細胞

在多種轉(zhuǎn)錄因子和信號通路共同調(diào)控下，前體脂肪細胞向成熟脂肪細胞分化，并伴隨一系列成脂基因和脂肪代謝相關(guān)酶基因的時序性表達。前體脂肪細胞分化經(jīng)歷3個階段：接觸抑制、克隆擴增、終末分化。第一階段前體脂肪細胞長滿進入細胞分裂停滯的G0期，細胞開始表達早期分化標志基因—前脂肪細胞因子()基因和脂蛋白酯酶(Lipoprotein lipase,)基因[20]。經(jīng)歷接觸抑制后，在促有絲分裂和促脂肪生成信號刺激(如胰島素、糖皮質(zhì)激素)下，前體脂肪細胞再次進入細胞周期并經(jīng)歷兩輪有絲分裂，此時有許多重要的轉(zhuǎn)錄因子開始表達，如過氧化物酶體增殖物激活受體γ(Peroxisome proliferator activated receptorγ, PPARγ)、CCAAT增強子結(jié)合蛋白家族(CCAAT/enhancer-binding proteins, C/EBPs)、固醇調(diào)節(jié)元件結(jié)合蛋白(Sterol regulatory element binding protein-1c, SREBP-1c)等，這些轉(zhuǎn)錄因子促進許多啟動脂肪合成和聚集的相關(guān)基因表達，如乙酰輔酶A脫羧酶(Acetyl-CoA carboxylase, ACC)、脂肪酸結(jié)合蛋白(Adipocyte fatty acid binding proteins, ap2)、硬脂酰輔酶A去飽和酶(Stearoyl-CoA desaturase, SCD)等。這一時期細胞數(shù)目明顯增多，形態(tài)發(fā)生顯著改變，由梭形逐漸變?yōu)闄E圓形，并伴隨著許多小脂肪滴形成[21]。隨后細胞進入終末分化階段，此時與甘油三酯代謝相關(guān)酶活性顯著升高，如ATP檸檬酸裂解酶、ACC、脂肪酸合成酶(Fatty acid synthetase, FAS)和3-磷酸甘油醛脫氫酶(Glyceraldehyde- 3-phosphate dehydrogenase, GAPDH)等。細胞胞質(zhì)中小脂肪滴逐漸匯聚成單一的大脂滴，并占據(jù)大部分胞質(zhì)，胞核被擠到靠近細胞膜的邊緣部分[22]。

2.2 棕色脂肪細胞

棕色脂肪細胞是高表達UCP-1的生熱型脂肪細胞，棕色脂肪細胞與肌細胞有共同的祖細胞，稱為MYF5(Myogenic factor 5)/PAX7(Paired-box 7)祖細胞，當(dāng)和兩個基因表達時，間充質(zhì)干細胞向MYF5/PAX7祖細胞分化。棕色脂肪細胞與肌細胞的前體細胞具有相似的基因表達模式和線粒體蛋白表達譜[17, 23]。MYF5/PAX7祖細胞在骨形態(tài)發(fā)生蛋白-7(Bone morphogenetic protein-7, BMP-7)、PPARγ、C/EBPs、過氧化物酶體增殖物激活受體α輔激活因子(Peroxisome proliferator activated receptor γ coactivator-1α, PGC-1α)和具有鋅指結(jié)構(gòu)的轉(zhuǎn)錄輔助調(diào)節(jié)因子(PR domain-containing 16, PRDM16)存在時分化為棕色脂肪細胞[16]，其中PRDM16是決定MYF5/PAX7祖細胞向棕色脂肪細胞分化的開關(guān)[24]。成熟的棕色脂肪細胞胞質(zhì)中有許多線粒體和微小脂滴。

2.3 米色脂肪細胞

米色脂肪細胞也是表達UCP-1的產(chǎn)熱脂肪細胞，最初發(fā)現(xiàn)于成年動物皮下白色脂肪組織(Subcutaneous WAT, sWAT)。sWAT在長期冷刺激、β3-腎上腺素受體激活劑、PPARγ激動劑等刺激下，一些細胞在形態(tài)學(xué)和生理學(xué)上表現(xiàn)出與棕色脂肪相似的特征，如出現(xiàn)多室微小脂滴、線粒體增多、UCP-1表達上升等[23]。盡管米色脂肪細胞在形成 過程中有許多基因與經(jīng)典棕色脂肪細胞表達相似，如和(Cell death- inducing Dff45 like effector)，但其也有自身的標志基因，如(Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain 1)(Transmembrane protein 26)和(T-box 1)[25]。

3 miRNA調(diào)控脂肪細胞分化

越來越多的研究表明，miRNA可以與脂肪細胞分化相關(guān)的轉(zhuǎn)錄因子和重要信號分子相互作用來調(diào)控脂肪形成[3]。近年來已有許多調(diào)控脂肪細胞分化的miRNA和靶基因被發(fā)現(xiàn)(表1)，miRNA調(diào)控脂肪細胞分化的網(wǎng)絡(luò)正在逐步完善(圖2)。

圖2 脂肪細胞分化miRNA調(diào)控網(wǎng)絡(luò)

FABP4：脂肪酸結(jié)合蛋白4；GLUT4：葡萄糖轉(zhuǎn)運體；ADIPOQ：脂聯(lián)素；LPL：脂蛋白酯酶；ACC：乙酰輔酶A脫羧酶；FAS：脂肪酸合成酶；Tbx1：T-box基因1；Tmem26：跨膜蛋白26；Zic-1：小腦鋅指蛋白1；Lhx-8：LIM同源盒基因8；LEF：淋巴增強子結(jié)合因子1；PGC-1α：過氧化物酶體增殖物激活受體γ輔激活因子1α；NICD:Notch胞內(nèi)結(jié)構(gòu)域；SMAD3：Sma和Mad相關(guān)蛋白3。

表1 miRNA調(diào)控脂肪細胞分化

注：PPARs：過氧化氫酶體增殖物激活受體；C/EBPs：CCAAT增強子結(jié)合蛋白；EID-1：EP300相互作用分化抑制因子1；Wnt/β-catenin：Wnt/β-連環(huán)蛋白；GSK3-β：糖原合成酶激酶3β；LRP6：低密度脂蛋白受體相關(guān)蛋白6；TCF：T細胞因子；MAPK：促分裂原活化蛋白激酶；ERK1? 2：細胞外調(diào)節(jié)蛋白激酶1/2；cAMP/PKA/CREB：腺苷酸環(huán)化酶/蛋白激酶A/環(huán)磷腺苷效應(yīng)元件結(jié)合蛋白；PI3K/Akt：磷脂酰肌醇3激酶/蛋白激酶B；IRS1：胰島素受體底物；ORP8：氧類固醇結(jié)合蛋白相關(guān)蛋白；PTN：多效生長因子；PDK1：3-磷酸肌醇依賴性蛋白激酶1；TGF-β：轉(zhuǎn)化生長因子- β；KLF：Kruppel樣因子；Runx2：Runt相關(guān)轉(zhuǎn)錄因子2；Cav-1：微囊蛋白1；DLK1：delta樣1同族物；PRDM16：鋅指轉(zhuǎn)錄因子PR結(jié)構(gòu)域包含蛋白16；UCP-1：解偶聯(lián)蛋白；Pde1b：磷酸二酯酶1b；Igfbp5：胰島素樣生長因子結(jié)合蛋白5；RIP140：受體相互作用蛋白140；ADAM17：解聚素-金屬蛋白酶17；Hoxc8：同源框基因8；FGFR1：成纖維細胞生長因子受體1；Pre-ad：前體脂肪細胞；hMADS：人多能脂肪干細胞；MSC：間充質(zhì)干細胞；ADSC：脂肪干細胞。

3.1 miRNA與白色脂肪細胞分化

PPARγ、C/EBPs是貫穿脂肪細胞分化進程最重要的轉(zhuǎn)錄因子，miRNA可以與這些轉(zhuǎn)錄因子直接或間接作用來調(diào)節(jié)細胞分化[3]。Kim等[26]和Lee等[27]發(fā)現(xiàn)miR-27a和miR-130a可以與的3′UTR區(qū)結(jié)合下調(diào)的表達量，同時在3T3-L1細胞分化過程中miR-27a和miR-130a表達逐漸下降，與表達呈負相關(guān)，而過表達miR-27a和miR-130a時，表達量下降，脂肪細胞分化程度減弱，這些研究表明miR-27a和miR-130a可以靶向作用于從而抑制脂肪細胞分化。Yang等[28]發(fā)現(xiàn)在人脂肪干細胞成脂誘導(dǎo)分化過程中miR-138表達量顯著下降，而過表達miR-138時，、和等成脂基因表達受到抑制，胞內(nèi)脂滴聚集減少，進一步研究表明miR-138可以與核共調(diào)節(jié)因子(EP300 interacting inhibitor of differentiation-1)3′UTR區(qū)結(jié)合下調(diào)表達。EID-1可以抑制TGF-β(Transforming growth factor-β)信號通路以促進脂肪形成，因此，miR-138可以下調(diào)靶基因，間接激活TGF-β信號通路從而抑制脂肪細胞分化。Sun等[29]和Tang等[30]發(fā)現(xiàn)在人間充質(zhì)干細胞(MSC)向脂肪細胞誘導(dǎo)分化過程中，miR-31可以靶向作用于脂肪細胞分化重要的轉(zhuǎn)錄因子，抑制脂肪細胞分化。Tang等[30]還發(fā)現(xiàn)miR-326也可以與作用抑制脂肪形成。Noriko等[31]通過芯片分析發(fā)現(xiàn)肥胖小鼠肝臟和脂肪中miR-335上調(diào)，且在3T3-L1細胞分化過程中，miR-335與成脂標志基因、和表達量呈正相關(guān)，但miR-335的靶基因和作用機制還有待研究。

miRNA還可以與信號轉(zhuǎn)導(dǎo)通路中關(guān)鍵分子的mRNA結(jié)合，通過影響細胞信號通路傳遞間接調(diào)控脂肪細胞的分化。Wnt/β-catenin信號通路對脂肪細胞分化具有非常重要的調(diào)節(jié)作用，激活Wnt通路可以抑制脂肪細胞分化[32]。Chen等[33]發(fā)現(xiàn)在3T3-L1分化過程中miR-344可以與Wnt信號通路分子(Glycogen synthase kinase 3-β)的3′UTR區(qū)結(jié)合，下調(diào)其表達量，使GSK3-β下游效應(yīng)分子β-catenin蛋白表達量上升，從而激活Wnt通路，抑制脂肪細胞分化。Chen等[34]發(fā)現(xiàn)miR-183靶向作用于Wnt信號通路分子(Low-density lipoprotein receptor-related protein 6)，抑制經(jīng)典Wnt途徑，從而促進3T3-L1前體脂肪細胞分化。ERK(Extracellular regulated protein kinases)、p38、JNK(c-Jun N-terminal kinase)共同構(gòu)成了MAPK(Mitogen-activated protein kinase)信號通路，MAPK信號通路被激活后，可以引發(fā)細胞一系列轉(zhuǎn)錄事件和細胞應(yīng)答[35]。Ling等[36]發(fā)現(xiàn)在3T3-L1分化過程中，miR-375能抑制ERK1?2 (Extracellular signal regulated kinases 1/2)磷酸化，通過ERK途徑上調(diào)PPARγ、C/EBPα，增加ap2表達和甘油三脂聚集，從而促進成脂。Chen等[37]在研究miR-143對脂肪干細胞(Adipose derived stem cells, ADSC)分化作用時發(fā)現(xiàn)，miR-143可以與MAPKK家族成員的3′UTR區(qū)結(jié)合影響脂肪形成，但是在不同分化階段中作用并非完全一致。在克隆擴增階段，過表達miR-143抑制分化，而在接觸抑制和終末分化階段，過表達miR-143促進分化。另外，Liu等[38]發(fā)現(xiàn)在3T3-L1分化中加入TNF-α引起miR-155的上調(diào)，miR-155可以與(cAMP- response element binding protein)的3′UTR區(qū)作用，通過cAMP/PKA/CREB信號通路抑制脂肪細胞分化。Mi等[39]發(fā)現(xiàn)miR-139-5p可以與和的3′UTR區(qū)結(jié)合，下調(diào)Notch1和IRS1表達，通過Notch信號通路和 IRS1/PI3K/Akt信號通路阻礙3T3-L1從克隆增殖期向終末分化期轉(zhuǎn)換，從而抑制脂肪細胞分化。

3.2 miRNA與棕色脂肪細胞分化

PGC-1α、PRDM16、PPARγ和C/EBPs等是棕色脂肪形成非常重要的轉(zhuǎn)錄因子，其中PRDM16是決定祖細胞向棕色脂肪細胞分化的開關(guān)[24]。Trajkovski等[40]和Yin等[41]發(fā)現(xiàn)小鼠在冷刺激后棕色脂肪增多，線粒體活性增強，而miR-133表達下降，進一步研究發(fā)現(xiàn)miR-133可以與的3′UTR區(qū)結(jié)合下調(diào)其表達量，因此冷刺激引起miR-133下調(diào)能夠促進棕色脂肪細胞分化。Chen 等[42]發(fā)現(xiàn)在棕色脂肪細胞分化過程中miR-155可以結(jié)合的3′UTR區(qū)抑制其表達，同時，一些成脂激素引起C/EBPβ上升可抑制miR-155的轉(zhuǎn)錄，miR-155和C/EBPβ構(gòu)成的雙向負反饋回路共同調(diào)控棕色脂肪形成。Sun等[43]用芯片鑒定出miR- 193b-365在棕色脂肪細胞分化過程中表達量顯著上升，miR-193b可以與(Insulin-like growth factor binding protein 5)和這兩個成肌相關(guān)的細胞因子結(jié)合，促進棕色脂肪細胞分化，抑制肌肉形成。Pan等[44]研究發(fā)現(xiàn)miR-378轉(zhuǎn)基因小鼠BAT增多，在BAT中miR-378可以與磷酸二酯酶(Phosphodiesterase, Pde1b)的3′UTR區(qū)結(jié)合抑制cAMP降解，胞內(nèi)cAMP含量升高，進而促進棕色脂肪形成。

3.3 miRNA與米色脂肪細胞分化

最新研究發(fā)現(xiàn)miRNA可以調(diào)控白色脂肪細胞棕色化，從而影響米色脂肪形成。Fu等[45]用慢病毒介導(dǎo)飲食誘導(dǎo)肥胖小鼠體內(nèi)miR-34a下調(diào)，發(fā)現(xiàn)其血脂降低，脂肪組織線粒體拷貝數(shù)和氧化功能增強，同時米色脂肪標志蛋白CD137和UCP-1表達顯著升高。后續(xù)研究發(fā)現(xiàn)miR-34a可以與成纖維細胞生長因子受體(Fibroblast growth factor-1 receptor,)的3′UTR區(qū)結(jié)合，引起FGFR1表達降低。當(dāng)miR-34a下調(diào)時，F(xiàn)GFR1表達升高，成纖維細胞生長因子21(FGF21)信號增強，而FGF21可以介導(dǎo)胞外調(diào)節(jié)激酶(ERK)磷酸化，通過MAPK信號通路促進米色脂肪形成。miR-34a的下調(diào)還可以增加PGC-1α脫乙酰作用，增強PGC-1α的轉(zhuǎn)錄活性，因此miR-34a可以抑制米色脂肪細胞分化。Hu等[46]用β3-腎上腺素激動劑處理或冷刺激小鼠，發(fā)現(xiàn)小鼠體內(nèi)miR-30b/c表達升高，且miR-30b/c可以靶向作用于(Receptor-interacting protein 140)，RIP140是脂肪代謝相關(guān)途徑酶或轉(zhuǎn)錄因子的輔阻遏物，RIP140的表達下降可以增加解偶聯(lián)蛋白UCP-1和Cidea表達，增加WAT產(chǎn)熱和棕色化。

4 展望

肥胖的發(fā)病率愈來愈高，肥胖引起的脂肪代謝紊亂并發(fā)癥正逐年上升，肥胖已經(jīng)成為影響人類健康的最大殺手[1]。近年來發(fā)現(xiàn)的米色脂肪細胞源于WAT，高表達線粒體內(nèi)膜標志蛋白UCP-1，可以增加脂肪組織產(chǎn)熱，為肥胖和脂肪代謝異常的治療開辟新途徑[25]。目前已經(jīng)發(fā)現(xiàn)了一些調(diào)控脂肪細胞分化的miRNA，它們作用于成脂相關(guān)的轉(zhuǎn)錄因子和信號通路共同調(diào)控脂肪形成，以維持機體脂肪代謝穩(wěn)態(tài)[3, 5]。但是miRNA對脂肪形成調(diào)控網(wǎng)絡(luò)尚需要進一步完善，尤其是調(diào)控米色脂肪形成的miRNA還需深度挖掘。研究3種脂肪細胞的起源及分化的分子機制，構(gòu)建miRNA對脂肪組織形成的調(diào)控網(wǎng)絡(luò)，利用miRNA介導(dǎo)和啟動BAT與WAT前體脂肪細胞產(chǎn)熱程序?qū)⒊蔀槲磥碇委煼逝值男路较騕47]。

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MicroRNA regulates animal adipocyte differentiation

Jinwei Zhang, Yi Luo, Yuhao Wang, Liujun He, Mingzhou Li, Xun Wang

Adipose tissues play a critical role in the regulation of energy metabolism and homeostasis, and is also an important endocrine organ. Adipocyte differentiation is a complicated physiological process during which mesenchymal stem cells differentiate into adipocytes. This process is synergistically regulated by a large number of transcription factors, hormones and signaling pathway molecules. As a class of endogenous non-coding RNA (ncRNA), microRNAs (miRNAs) regulate gene expression mainly through post-transcriptional translational repression. In recent years, numerous studies have demonstrated that miRNA could have an impact on adipocyte differentiation and adipogenesis by modulating the expression levels of several adipogenic transcription factors and key signaling molecules. In this review, we summarize the mechanism of miRNA in regulating the differentiation of white/brown/beige adipocytes and the relevant signaling pathways and key factors, in the hope of providing theoretical guidance and new thoughts for treating obesity and other metabolic diseases.

miRNA; white adipocyte; brown adipocyte; beige adipocyte; differentiation

2015-05-20;

2015-08-17

國家高技術(shù)研究發(fā)展計劃(863計劃)項目(編號：2013AA102502)，四川省教育廳重點項目(編號：15ZA0008/15ZA0003)，四川省青年科技創(chuàng)新研究團隊(編號：2015TD0012)，長江學(xué)者和創(chuàng)新團隊發(fā)展計劃(編號：IRT13083)和重慶市農(nóng)發(fā)資金項目(編號：13410)資助

張進威，碩士研究生，專業(yè)方向：豬遺傳育種與繁殖。E-mail: JinweiZhang50@163.com

王訊，副教授，碩士生導(dǎo)師，研究方向：豬遺傳育種與繁殖。E-mail:wangxun99@163.com

10.16288/j.yczz.15-233

網(wǎng)絡(luò)出版時間: 2015-9-23 17:06:41

URL: http://www.cnki.net/kcms/detail/11.1913.R.20150923.1706.004.html

(責(zé)任編委: 李輝)