An Amino Acid Signature Associated with Obesity Predicts 2-Year Risk of Hypertriglyceridemia in School-Age Children

Sofia Moran-Ramos,Paola León-Mimila,Ruth Gutierrez-Aguilar,Blanca E Del-Río-Navarro,Elvira Ocampo-Medina,Carlos A Aguilar-Salinas,Samuel Canizales-Quinteros,Blanca E López-Contreras,Adriana Huertas-Vázquez,Isabel Ibarra-Gonzalez,Ricardo Villarruel-Vazquez,Roxana Gutierrez-Vidal,Hugo Villamil-Ramírez,Erandi Serrano-Carbajal,Marcela Vela-Amieva,Joel Vega-Badillo,Luis Macías-Kauffer,Teresa Villarreal-Molina

doi:10.1038/s41598-017-05765-4

Abstract

Childhood obesity is associated with a number of metabolic abnormalities leading to increased cardiovascular risk. Metabolites can be useful as early biomarkers and new targets to promote early intervention beginning in school age. Thus, we aimed to identify metabolomic profiles associated with obesity and obesity-related metabolic traits. We used data from the Obesity Research Study for Mexican children (ORSMEC) in Mexico City and included a case control (n = 1120), cross-sectional (n = 554) and a longitudinal study (n = 301) of 6–12-year-old children. Forty-two metabolites were measured using electrospray MS/MS and multivariate regression models were used to test associations of metabolomic profiles with anthropometric, clinical and biochemical parameters. Principal component analysis showed a serum amino acid signature composed of arginine, leucine/isoleucine, phenylalanine, tyrosine, valine and proline significantly associated with obesity (OR = 1.57; 95%CI 1.45–1.69, P = 3.84 × 10−31) and serum triglycerides (TG) (β = 0.067, P = 4.5 × 10−21). These associations were validated in the cross-sectional study (P < 0.0001). In the longitudinal cohort, the amino acid signature was associated with serum TG and with the risk of hypertriglyceridemia after 2 years (OR = 1.19; 95%CI 1.03-1.39, P = 0.016). This study shows that an amino acid signature significantly associated with childhood obesity, is an independent risk factor of future hypertriglyceridemia in children.

Highlights

Obesity represents a major global health problem in adults and children
The objective of the present study was to identify metabolomic profiles associated with obesity and metabolic traits in Mexican children using both a case-control study and a longitudinal cohort-based approach
To analyze the metabolomics profile, we used principal component analysis (PCA) that cluster metabolites into highly correlated species

Summary

Introduction

Obesity represents a major global health problem in adults and children. In Mexico, according to the National Health and Nutrition survey 2012, the prevalence of overweight and obesity is 71.2% in adults and 34.3% in children[1]. Pediatric obesity is strongly associated with a number of metabolic abnormalities such as dyslipidemia, insulin resistance and hypertension. All the latter are well known risk factors for cardiovascular disease[2], the leading worldwide cause of mortality[3]. Branched-chain (BCAA) and aromatic amino acid (AA) serum levels are increased in obesity in humans and animal models[9, 10], and have been associated with current and future development of insulin resistance in adults and children[11,12,13]. The objective of the present study was to identify metabolomic profiles associated with obesity and metabolic traits in Mexican children using both a case-control study and a longitudinal cohort-based approach

Objectives

Methods

Results

Conclusion