ESPE Abstracts (2014) 82 P-D-1-1-111

A Multiplatform Non-targeted Metabolomics Approach to Investigate Insulin Resistance Associated to Obesity in Childhood

Annalaura Mastrangeloa, Gabriel Martos-Morenob, Antonia Garcíaa, Francisco Rupéreza, Julie Chowenb, Luis Pérez-Juradoc, Coral Barbasa & Jesús Argenteb

aCEMBIO, Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Boadilla del Monte, Madrid, Spain; bHospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid, Pediatrics and Pediatric Endocrinology, Instituto de Investigación La Princesa, Centro de Investigación Biomédica en Red de fi, Madrid, Spain; cDepartment of Genetics, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Hospital del Mar Research Institute (IMIM), Universitat Pompeu Fabra, Barcelona, Spain

Background: Childhood obesity is often associated with insulin resistance (IR), which is a key risk factor for the development of comorbidities. The etiologic relation between insulin resistance and obesity is still not completely understood.

Objective: In this study a multiplatform metabolomics approach was applied for the first time to elucidate the metabolic alterations in obese children with or without IR. Metabolomics is the revolutionary strategy of the last century capable of interpreting the interaction of the genetic and environmental factors by studying the final effectors of a process.

Methods: Plasma from 60 prepubertal obese children between 5 and 13 years, 30 males and 30 females, which were insulin (n=30) or non-insulin resistant (n=30) were analyzed by using LC-ESI-MS-QTOF, GC-EI-MS-Q and CE-ESI-MS-QTOF (Agilent, USA) in a non-targeted approach. Together the three techniques provided information about several thousand compounds.

Results: Once the valuable information from the analytical data was mined, the two groups were compared and 85 significant differences (P value <0.05) were unveiled. Subtle differences existed between groups that were magnified when comparisons between sexes were made. Bile acids and their derivatives represented the most prominent changes indicating the influence of the gut microbiota on the host metabolism. In addition, branched-chain amino acids, lactic acid, pyruvic acid, lysophophocholine, and decanamide were significantly different. These are usually altered in obesity and our results suggest they may have a possible function in the predisposition towards complications such as IR.

Conclusion: This study reveals the potential of metabolomics to highlight unexpected pre-pubertal sex differences and to detect subtle differences between two conditions highly linked but not unequivocally correlated to the onset of comorbidities, which could help to elucidate processes in their early stage where the preventive action could play an essential role.