Structural Biochemistry Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.
Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Barcelona, Spain.
PLoS One. 2018 Jul 13;13(7):e0199351. doi: 10.1371/journal.pone.0199351. eCollection 2018.
The present study was aimed at determining the metabolic profile of PMNs in obese subjects, and to explore its potential relationship with insulin resistance (IR). To achieve this goal, a pilot clinical study was performed using PMNs from 17 patients with obesity and IR, and 17 lean controls without IR, which was validated in an additional smaller cohort (consisting of 10 patients and 10 controls). PMNs were isolated from peripheral blood and nuclear magnetic resonance was used to perform the metabolomic analysis. A total of 48 metabolites were quantified. The main metabolic change found in PMNs was a significant increase in 2-aminoisobutyric acid with a direct correlation with HOMA-IR (p<0.001), BMI (p<0.000001) and waist circumference (p<0.000001). By contrast, a decrease of 3-hydroxyisovalerate was observed with an inverse correlation with HOMA-IR (p = 0.001), BMI (p = 0.001) and waist circumference (p = 0.0001). Notably, the metabolic profile in plasma was different than that obtained in PMNs. In summary, our results suggest that the change in 3-hydroxyisovalerate and 2-aminoisobutyric is the key metabolic fingerprint in PMNs of obese subjects with IR. In addition, our methodology could be an easy and reliable tool for monitoring the effect of treatments in the setting of precision medicine.
本研究旨在确定肥胖患者中性粒细胞的代谢特征，并探讨其与胰岛素抵抗（IR）的潜在关系。为了实现这一目标，我们进行了一项初步的临床研究，使用来自 17 名肥胖伴 IR 患者和 17 名不伴 IR 的瘦对照者的中性粒细胞进行验证，并在一个较小的队列（包括 10 名患者和 10 名对照者）中进行了验证。从外周血中分离中性粒细胞，并使用核磁共振进行代谢组学分析。共定量了 48 种代谢物。中性粒细胞中发现的主要代谢变化是 2-氨基异丁酸显著增加，与 HOMA-IR（p<0.001）、BMI（p<0.000001）和腰围（p<0.000001）直接相关。相比之下，3-羟基异戊酸减少，与 HOMA-IR（p=0.001）、BMI（p=0.001）和腰围（p=0.0001）呈负相关。值得注意的是，血浆中的代谢谱与中性粒细胞中的代谢谱不同。总之，我们的研究结果表明，3-羟基异戊酸和 2-氨基异丁酸的变化是肥胖伴 IR 患者中性粒细胞的关键代谢特征。此外，我们的方法可以作为一种简单可靠的工具，用于监测精准医学治疗效果。
