Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
Waters Corporation, Wilmslow, United Kingdom.
Prostaglandins Leukot Essent Fatty Acids. 2020 Sep;160:102157. doi: 10.1016/j.plefa.2020.102157. Epub 2020 Jun 27.
Obesity is associated with adipose tissue inflammation which in turn drives insulin resistance and the development of type 2 diabetes. Oxylipins are a collection of lipid metabolites, subdivided in different classes, which are involved in inflammatory cascades. They play important roles in regulating adipose tissue homeostasis and inflammation and are therefore putative biomarkers for obesity-associated adipose tissue inflammation and the subsequent risk of type 2 diabetes onset. The objective for this study is to design an assay for a specific oxylipin class and evaluate these as potential prognostic biomarker for obesity-associated adipose tissue inflammation and type 2 diabetes.
An optimized workflow was developed to extract oxylipins from plasma using solid-phase extraction followed by analysis using ultra-high performance liquid chromatography coupled to a triple quadrupole mass spectrometer in multiple reaction monitoring mode. This workflow was applied to clinical plasma samples obtained from obese-type 2 diabetes patients and from lean and obese control subjects.
The assay was analytically validated and enabled reproducible analyses of oxylipins extracted from plasma with acceptable sensitivities. Analysis of clinical samples revealed discriminative values for four oxylipins between the type 2 diabetes patients and the lean and obese control subjects, viz. PGF, PGE, 15-keto-PGE and 13,14-dihydro-15-keto-PGE. The combination of PGF and 15-keto-PGE had the most predictive value to discriminate type 2 diabetic patients from lean and obese controls.
This proof-of-principle study demonstrates the potential value of oxylipins as biomarkers to discriminate obese individuals from obese-type 2 diabetes patients.
肥胖与脂肪组织炎症有关，而脂肪组织炎症又会导致胰岛素抵抗和 2 型糖尿病的发生。氧化脂质是一类脂质代谢物的集合，可分为不同的类别，它们参与炎症级联反应。它们在调节脂肪组织稳态和炎症方面发挥着重要作用，因此被认为是肥胖相关脂肪组织炎症和随后 2 型糖尿病发病风险的潜在生物标志物。本研究的目的是设计一种特定氧化脂质类别的测定方法，并评估其作为肥胖相关脂肪组织炎症和 2 型糖尿病潜在预后生物标志物的潜力。
开发了一种优化的工作流程，使用固相萃取从血浆中提取氧化脂质，然后使用超高效液相色谱-三重四极杆质谱联用仪在多重反应监测模式下进行分析。该工作流程应用于从肥胖 2 型糖尿病患者和瘦和肥胖对照受试者获得的临床血浆样本。
该测定方法经过分析验证，能够对从血浆中提取的氧化脂质进行可重复的分析，具有可接受的灵敏度。对临床样本的分析显示，在 2 型糖尿病患者和瘦和肥胖对照组之间，四种氧化脂质（PGF、PGE、15-酮-PGE 和 13,14-二氢-15-酮-PGE）具有可区分的值。PGF 和 15-酮-PGE 的组合具有区分 2 型糖尿病患者与瘦和肥胖对照组的最大预测价值。
这项原理验证研究表明，氧化脂质作为生物标志物，有潜力区分肥胖个体和肥胖 2 型糖尿病患者。
