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Jul 13, 2018 - and Metabolism Research Unit, Vall d'Hebron Research Institute, .... 14) and Vall d'Hebron University Hospital (protocol number PR(AG) ...
RESEARCH ARTICLE

Metabolic fingerprint of insulin resistance in human polymorphonuclear leucocytes Martina Palomino-Scha¨tzlein1*, Rafael Simo´2,3*, Cristina Herna´ndez2,3, Andreea Ciudin2,3, Pablo Mateos-Gregorio1, Antonio Herna´ndez-Mijares4, Antonio Pineda-Lucena1,5, Jose´ Rau´l Herance6*

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1 Structural Biochemistry Laboratory, Centro de Investigacio´n Prı´ncipe Felipe, Valencia, Spain, 2 Diabetes and Metabolism Research Unit, Vall d’Hebron Research Institute, Barcelona, Spain, 3 CIBERDEM (Instituto de Salud Carlos III), Madrid, Spain, 4 Service of Endocrinology, University Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain, 5 Drug Discovery Unit, Instituto de Investigacio´n Sanitaria La Fe, Hospital Universitario y Polite´cnico La Fe, Valencia, Spain, 6 Medical Molecular Imaging Research Group, Vall d’Hebron Research Institute, CIBBIMNanomedicine, CIBERbbn, Barcelona, Spain * [email protected] (JRH); [email protected] (MP); [email protected] (RS)

Abstract OPEN ACCESS Citation: Palomino-Scha¨tzlein M, Simo´ R, Herna´ndez C, Ciudin A, Mateos-Gregorio P, Herna´ndez-Mijares A, et al. (2018) Metabolic fingerprint of insulin resistance in human polymorphonuclear leucocytes. PLoS ONE 13(7): e0199351. https://doi.org/10.1371/journal. pone.0199351 Editor: Clemens Fu¨rnsinn, Medical University of Vienna, AUSTRIA Received: February 9, 2018 Accepted: June 6, 2018 Published: July 13, 2018 Copyright: © 2018 Palomino-Scha¨tzlein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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