Lipidomics Reveals Associations of Phospholipids With Obesity and Insulin Resistance in Young Adults
Lipidomics Reveals Associations of Phospholipids With Obesity and Insulin Resistance in Young Adults
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DOI：
10.1210/jc.2015-3525
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发表时间：
2016-03-01
影响因子：
5.8
通讯作者：
Oddy, Wendy H.
中科院分区：
文献类型：
--
作者：
Rauschert, Sebastian;Uhl, Olaf;Oddy, Wendy H.
背景：肥胖及相关疾病已成为全球公共卫生负担。识别生物标志物将有助于更好地理解与肥胖相关的潜在机制以及导致胰岛素抵抗（IR）和糖尿病的途径。目的：本研究旨在通过以人群为基础的青年队列血浆样本，确定与肥胖和IR相关的脂质组学生物标志物。设计与背景：西澳大利亚妊娠队列（Raine）研究从1989年到1991年招募了2900名孕妇。2010年3月至2012年4月期间进行了为期20年的随访。参与者和样本：使用基于质谱的代谢组学分析了1176名20岁受试者的血浆样本。主要结局指标：分析物与肥胖和IR标志物的关联，包括体重指数、腰围、稳态模型评估（HOMA-IR）和胰岛素。分析以体重指数分层，并根据生活方式和其他因素进行调整。结果：腰围与7种鞘磷脂和5种二酰基磷脂酰胆碱呈正相关，与2种溶血磷脂酰胆碱呈负相关。HOMA-IR与两种二酰基磷脂酰胆碱呈负相关，与一种溶血磷脂酰胆碱和一种二酰基磷脂酰胆碱呈正相关。在HOMA-IR模型中，肥胖/超重组未发现显著相关性。正常体重组溶血磷脂酰胆碱增加1个。结论：鞘磷脂，特别是具有两个双键的鞘磷脂和溶血磷脂在正常体重和肥胖受试者之间可能存在区别作用，而不受低密度脂蛋白胆固醇和高密度脂蛋白胆固醇浓度的影响。我们的研究结果表明，IR的发展与体重状态相关，溶血磷脂酰胆碱C14:0是非肥胖IR的关键代谢物。
Context: Obesity and related diseases have become a global public health burden. Identifying biomarkers will lead to a better understanding of the underlying mechanisms associated with obesity and the pathways leading to insulin resistance (IR) and diabetes.Objective: This study aimed to identify the lipidomic biomarkers associated with obesity and IR using plasma samples from a population-based cohort of young adults.Design and Setting: The Western Australian Pregnancy Cohort (Raine) study enrolled 2900 pregnant women from 1989 to 1991. The 20-year follow-up was conducted between March 2010 and April 2012.Participants and Samples: Plasma samples from 1176 subjects aged 20 years were analyzed using mass spectrometry-based metabolomics.Main Outcome Measures: Associations of analytes with markers of obesity and IR including body mass index, waist circumference, homeostasis model assessment (HOMA-IR), and insulin were examined. Analyses were stratified by body mass index and adjusted for lifestyle and other factors.Results: Waist circumference was positively associated with seven sphingomyelins and five diacylphosphatidylcholines and negatively associated with two lysophosphatidylcholines. HOMA-IR was negatively associated with two diacylphosphatidylcholines and positively with one lysophosphatidylcholine and one diacylphosphatidylcholine. No significant association was found in the obese/overweight group of the HOMA-IR model. In the normal-weight group, one lysophosphatidylcholine was increased.Conclusion: A possible discriminative effect of sphingomyelins, particularly those with two double bonds, and lysophosphatidylcholines was identified between subjects with normal weight and obesity independent of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentrations. Our results suggest weight status-dependent mechanisms for the development of IR with lysophosphatidylcholine C14:0 as a key metabolite in nonobese IR.