Whole Serum 3D LC-nESI-FTMS Quantitative Proteomics Reveals Sexual Dimorphism in the Milieu Interieur of Overweight and Obese Adults
Whole Serum 3D LC-nESI-FTMS Quantitative Proteomics Reveals Sexual Dimorphism in the Milieu Interieur of Overweight and Obese Adults
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DOI：
10.1021/pr5003406
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发表时间：
2014-11-01
影响因子：
4.4
通讯作者：
Garbis, Spiros D.
中科院分区：
文献类型：
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作者：
Al-Daghri, Nasser M.;Al-Attas, Omar S.;Garbis, Spiros D.
将性别特异性差异与肥胖的分子病因学联系起来主要是基于缺乏内在表型洞察力的基因组和转录组学证据，并且不适用于人体的细胞外液区室或微环境。为了满足这一需求，本研究使用具有合并生物学和技术重复的多重设计来分析年龄匹配的非糖尿病超重和肥胖女性（n = 28）和男性（n = 31）的全血清蛋白质组。为了绕过基于免疫耗竭的策略的基本限制，使用了通过尺寸排阻色谱法（SuPrE-SEC）进行亚蛋白质组富集，然后进行iTRAQ 2D-LC-nESI-FTMS分析。该研究导致了2472种蛋白质的可重复分析（肽FDR <5%，q < 0.05）。共有248种蛋白质在男性和女性之间表现出显著的调节（p < 0.05），其映射到与β-雌二醇、脂质和前列腺素类代谢、维生素D功能、免疫/炎症以及补体和凝血级联相关的途径。全血清中性别特异性差异的这种新的内表型特征证实并扩展了先前生理学和药理学研究的结果，这些研究在组织和细胞的基因组和转录组水平上探索性二态性。总之，人类肥胖的多因素和多效性的性质表现出性二态性的循环蛋白质组的重要性，临床研究设计。
Linking gender-specific differences to the molecular etiology of obesity has been largely based on genomic and transcriptomic evidence lacking endophenotypic insight and is not applicable to the extracellular fluid compartments, or the milieu interieur, of the human body. To address this need, this study profiled the whole serum proteomes of age-matched nondiabetic overweight and obese females (n = 28) and males (n = 31) using a multiplex design with pooled biological and technical replicates. To bypass basic limitations of immunodepletion-based strategies, subproteome enrichment by size-exclusion chromatography (SuPrE-SEC) followed by iTRAQ 2D-LC-nESI-FTMS analysis was used. The study resulted in the reproducible analysis of 2472 proteins (peptide FDR < 5%, q < 0.05). A total of 248 proteins exhibited significant modulation between men and women (p < 0.05) that mapped to pathways associated with beta-estradiol, lipid and prostanoid metabolism, vitamin D function, immunity/inflammation, and the complement and coagulation cascades. This novel endophenotypic signature of gender-specific differences in whole serum confirmed and expanded the results of previous physiologic and pharmacologic studies exploring sexual dimorphism at the genomic and transcriptomic level in tissues and cells. Conclusively, the multifactorial and pleiotropic nature of human obesity exhibits sexual dimorphism in the circulating proteome of importance to clinical study design.