近日，国际著名杂志《美国国家科学院院刊》（PNAS）在线刊登了中科院大连化学物理研究所许国旺研究员领导的研究组的研究成果，研究小组利用其构建的代谢组学技术平台取得重要科研成果。他们与中科院动物研究所康乐院士研究组合作，首次发现了肉碱类代谢物在飞蝗两型转变过程中的关键调控作用。
代谢组学作为系统生物学的分支，在生命科学研究中具有广阔的应用空间与巨大的实用价值。飞蝗散居型和群居型之间的转变（型变）正是复杂生物现象的典型代表，是蝗灾爆发的关键生物学基础。揭示飞蝗型变背后隐藏的生物调控机制具有重要的现实意义。多年来，康乐研究组致力于利用基因组学手段来破解这一谜题，并深刻认识到型变调控机制的阐释迫切需要系统生物学的深度介入。两个课题组决定开展跨学科协作研究，依托大连化物所的代谢组学平台，从血淋巴代谢物层次上来探寻飞蝗型变的分子基础，提出了新的型变调控机制。
研究人员首先利用超高效液相色谱/质谱和气相色谱/质谱联用方法，剖析了散居型与群居型飞蝗间的代谢表型差异，对氨基酸、脂质与酰基肉碱等差异代谢物进行了生物功能富集分析，明确了型变调控相关的代谢通路。随后，又利用代谢轨迹分析，对种群密度干预过程中飞蝗代谢模式的演变规律进行了动态描述，发现肉碱类代谢物呈现出与型变高度相关的时间序列变化特征。在此基础上，通过药物注射和基因干扰等功能验证实验，证实了肉碱类代谢物在飞蝗型变中发挥的关键调控作用。
这一新发现，不但突破了之前对型变生物机制认识的局限性，而且将为研究其他物种的表型可塑性现象提供启发，是凸显代谢组学巨大生物学研究价值的又一力证。
十年来，大连化物所1808组依托其在色谱领域的深厚积累，始终围绕着“高分辨分离与分析”这一学科发展主线，辅以具有自主知识产权的化学计量学信息处理系统开发，致力于打造国际一流的代谢组学技术平台。构建了以色谱—质谱联用技术为特色的代谢组学研究平台。除飞蝗的研究外，该组最近与第二军医大学附属东方肝胆外科医院王红阳院士在肝癌标志物的代谢组学研究（Mol Cell Proteomics. 2012 Feb；11(2)：M111.010694.）、与复旦大学附属妇产科医院徐丛剑教授等在卵巢癌早期诊断标志物的代谢组学研究（J Proteome Res. 2011 May 6；10(5)：2625-32.）也取得了广受关注的成果。（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.
