Wigger Leonore, Cruciani-Guglielmacci Céline, Nicolas Anthony, Denom Jessica, Fernandez Neïké, Fumeron Frédéric, Marques-Vidal Pedro, Ktorza Alain, Kramer Werner, Schulte Anke, Le Stunff Hervé, Liechti Robin, Xenarios Ioannis, Vollenweider Peter, Waeber Gérard, Uphues Ingo, Roussel Ronan, Magnan Christophe, Ibberson Mark, Thorens Bernard
Vital-IT Group, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
Unité de Biologie Fonctionnelle et Adaptative (BFA), CNRS UMR 8251, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France.
Cell Rep. 2017 Feb 28;18(9):2269-2279. doi: 10.1016/j.celrep.2017.02.019.
Plasma metabolite concentrations reflect the activity of tissue metabolic pathways and their quantitative determination may be informative about pathogenic conditions. We searched for plasma lipid species whose concentrations correlate with various parameters of glucose homeostasis and susceptibility to type 2 diabetes (T2D). Shotgun lipidomic analysis of the plasma of mice from different genetic backgrounds, which develop a pre-diabetic state at different rates when metabolically stressed, led to the identification of a group of sphingolipids correlated with glucose tolerance and insulin secretion. Quantitative analysis of these and closely related lipids in the plasma of individuals from two population-based prospective cohorts revealed that specific long-chain fatty-acid-containing dihydroceramides were significantly elevated in the plasma of individuals who will progress to diabetes up to 9 years before disease onset. These lipids may serve as early biomarkers of, and help identify, metabolic deregulation in the pathogenesis of T2D.
血浆代谢物浓度反映了组织代谢途径的活性，对其进行定量测定可能有助于了解致病情况。我们寻找了血浆脂质种类，其浓度与葡萄糖稳态的各种参数以及2型糖尿病（T2D）易感性相关。对来自不同遗传背景的小鼠血浆进行鸟枪法脂质组学分析，这些小鼠在代谢应激时以不同速率发展为糖尿病前期状态，结果鉴定出一组与葡萄糖耐量和胰岛素分泌相关的鞘脂。对来自两个基于人群的前瞻性队列个体血浆中的这些脂质及密切相关脂质进行定量分析发现，特定含长链脂肪酸的二氢神经酰胺在疾病发作前长达9年将进展为糖尿病的个体血浆中显著升高。这些脂质可能作为T2D发病机制中代谢失调的早期生物标志物，并有助于识别这种失调。
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