Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans
Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans
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DOI：
10.1016/j.celrep.2017.02.019
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发表时间：
2017-02-28
期刊：
影响因子：
8.8
通讯作者：
Thorens, Bernard
中科院分区：
文献类型：
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作者：
Wigger, Leonore;Cruciani-Guglielmacci, Celine;Thorens, Bernard
血浆代谢物浓度反映了组织代谢途径的活性，其定量测定可提供有关致病条件的信息。我们寻找血浆脂质种类，其浓度与葡萄糖稳态的各种参数和2型糖尿病（T2D）的易感性相关。来自不同遗传背景的小鼠血浆的鸟枪式脂质组学分析导致鉴定了一组与葡萄糖耐量和胰岛素分泌相关的鞘脂，所述小鼠在代谢应激时以不同速率发展糖尿病前期状态。对来自两个基于人群的前瞻性队列的个体的血浆中这些和密切相关的脂质的定量分析显示，在疾病发作前9年将进展为糖尿病的个体的血浆中，特定的长链含脂肪酸的二氢神经酰胺显著升高。这些脂质可作为T2D发病机制中代谢失调的早期生物标志物，并有助于识别。
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.