Serum metabolites associated with increased insulin resistance and low cardiorespiratory fitness in overweight adolescents

Background and Aims Obesity affects metabolism, increasing the risk of developing non-communicable diseases in adolescence, due to excess adipose tissue and low cardiorespiratory fitness (CRF). The metabolomics approach allows the elucidation of metabolites, which may have the concentrations altered by several factors, such as body composition (BC). We aimed to analyze the metabolomic profile of adolescents with normal and overweight and associate the metabolites with clinical markers related to BC, insulin resistance (IR), and CRF. Methods and Results The sample was composed of 57 adolescents, divided into normal-weight (NWG, n = 24) and overweight (OWG, n = 33) groups. They underwent blood collection, anthropometric, BC, and CRF assessment. Blood serum samples were analyzed by 1H-NMR spectroscopy (600 MHz). The OWG presented higher values of body weight (BW), body mass index (BMI), waist circumference (WC), fasting glucose, insulin, IR, cholesterol, percentage of fat mass (% FM), and lower levels of V O2peak compared to NWG. The OWG presented lower concentrations of 3-hydroxyisovalerate, glutamate, and methionine, as well as higher concentrations of aspartate, asparagine, creatine, glycerol, myo-inositol, proline, pyruvate, tyrosine, and valerate compared to NWG. The concentrations of glutamate, myo-inositol, creatine, methionine, and valerate correlated with % FM, pyruvate, and valerate positively correlated with IR, while glutamate, tyrosine, and valerate negatively correlated with CRF. Conclusion Body composition changes the metabolomic profile of adolescents, and the altered metabolites are associated with increased IR and low CRF. These results suggest new targets for health monitoring, prevention of cardiovascular and metabolic diseases in adolescents.