近日，國(guó)際著名雜志《美國(guó)國(guó)家科學(xué)院院刊》（PNAS）在線(xiàn)刊登了中科院大連化學(xué)物理研究所許國(guó)旺研究員領(lǐng)導(dǎo)的研究組的研究成果,，研究小組利用其構(gòu)建的代謝組學(xué)技術(shù)平臺(tái)取得重要科研成果,。他們與中科院動(dòng)物研究所康樂(lè)院士研究組合作,，首次發(fā)現(xiàn)了肉堿類(lèi)代謝物在飛蝗兩型轉(zhuǎn)變過(guò)程中的關(guān)鍵調(diào)控作用。
代謝組學(xué)作為系統(tǒng)生物學(xué)的分支,，在生命科學(xué)研究中具有廣闊的應(yīng)用空間與巨大的實(shí)用價(jià)值,。飛蝗散居型和群居型之間的轉(zhuǎn)變（型變）正是復(fù)雜生物現(xiàn)象的典型代表，是蝗災(zāi)爆發(fā)的關(guān)鍵生物學(xué)基礎(chǔ),。揭示飛蝗型變背后隱藏的生物調(diào)控機(jī)制具有重要的現(xiàn)實(shí)意義,。多年來(lái)，康樂(lè)研究組致力于利用基因組學(xué)手段來(lái)破解這一謎題,，并深刻認(rèn)識(shí)到型變調(diào)控機(jī)制的闡釋迫切需要系統(tǒng)生物學(xué)的深度介入,。兩個(gè)課題組決定開(kāi)展跨學(xué)科協(xié)作研究，依托大連化物所的代謝組學(xué)平臺(tái),，從血淋巴代謝物層次上來(lái)探尋飛蝗型變的分子基礎(chǔ),，提出了新的型變調(diào)控機(jī)制。
研究人員首先利用超高效液相色譜/質(zhì)譜和氣相色譜/質(zhì)譜聯(lián)用方法,，剖析了散居型與群居型飛蝗間的代謝表型差異,，對(duì)氨基酸,、脂質(zhì)與酰基肉堿等差異代謝物進(jìn)行了生物功能富集分析,，明確了型變調(diào)控相關(guān)的代謝通路,。隨后，又利用代謝軌跡分析,，對(duì)種群密度干預(yù)過(guò)程中飛蝗代謝模式的演變規(guī)律進(jìn)行了動(dòng)態(tài)描述,，發(fā)現(xiàn)肉堿類(lèi)代謝物呈現(xiàn)出與型變高度相關(guān)的時(shí)間序列變化特征。在此基礎(chǔ)上,，通過(guò)藥物注射和基因干擾等功能驗(yàn)證實(shí)驗(yàn),，證實(shí)了肉堿類(lèi)代謝物在飛蝗型變中發(fā)揮的關(guān)鍵調(diào)控作用。
這一新發(fā)現(xiàn),，不但突破了之前對(duì)型變生物機(jī)制認(rèn)識(shí)的局限性,，而且將為研究其他物種的表型可塑性現(xiàn)象提供啟發(fā)，是凸顯代謝組學(xué)巨大生物學(xué)研究?jī)r(jià)值的又一力證,。
十年來(lái),，大連化物所1808組依托其在色譜領(lǐng)域的深厚積累，始終圍繞著“高分辨分離與分析”這一學(xué)科發(fā)展主線(xiàn),，輔以具有自主知識(shí)產(chǎn)權(quán)的化學(xué)計(jì)量學(xué)信息處理系統(tǒng)開(kāi)發(fā),，致力于打造國(guó)際一流的代謝組學(xué)技術(shù)平臺(tái)。構(gòu)建了以色譜—質(zhì)譜聯(lián)用技術(shù)為特色的代謝組學(xué)研究平臺(tái),。除飛蝗的研究外,，該組最近與第二軍醫(yī)大學(xué)附屬東方肝膽外科醫(yī)院王紅陽(yáng)院士在肝癌標(biāo)志物的代謝組學(xué)研究（Mol Cell Proteomics. 2012 Feb；11(2)：M111.010694.）,、與復(fù)旦大學(xué)附屬婦產(chǎn)科醫(yī)院徐叢劍教授等在卵巢癌早期診斷標(biāo)志物的代謝組學(xué)研究（J Proteome Res. 2011 May 6,；10(5)：2625-32.）也取得了廣受關(guān)注的成果。（生物谷Bioon.com）
doi:10.1073/pnas.1119155109
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Metabolomic analysis reveals that carnitines are key regulatory metabolites in phase transition of the locusts
Rui Wua,1, Zeming Wub,1, Xianhui Wanga,1, Pengcheng Yanga, Dan Yua, Chunxia Zhaob, Guowang Xub,2, and Le Kanga,2
Phenotypic plasticity occurs prevalently and plays a vital role in adaptive evolution. However, the underlying molecular mechanisms responsible for the expression of alternate phenotypes remain unknown. Here, a density-dependent phase polyphenism of Locusta migratoria was used as the study model to identify key signaling molecules regulating the expression of phenotypic plasticity. Metabolomic analysis, using high-performance liquid chromatography and gas chromatography–mass spectrometry, showed that solitarious and gregarious locusts have distinct metabolic profiles in hemolymph. A total of 319 metabolites, many of which are involved in lipid metabolism, differed significantly in concentration between the phases. In addition, the time course of changes in the metabolic profiles of locust hemolymph that accompany phase transition was analyzed. Carnitine and its acyl derivatives, which are involved in the lipid β-oxidation process, were identified as key differential metabolites that display robust correlation with the time courses of phase transition. RNAi silencing of two key enzymes from the carnitine system, carnitine acetyltransferase and palmitoyltransferase, resulted in a behavioral transition from the gregarious to solitarious phase and the corresponding changes of metabolic profiles. In contrast, the injection of exogenous acetylcarnitine promoted the acquisition of gregarious behavior in solitarious locusts. These results suggest that carnitines mediate locust phase transition possibly through modulating lipid metabolism and influencing the nervous system of the locusts.
