ESPE Abstracts

Background: Obesity is one of the major risk factor for metabolic and cardiovascular disorders, and its global prevalence has increased exponentially in the last decades. Excessive weight gained during early childhood increases long-term risk; however, reversing this condition during early-life reduces risk, improving children’s quality of life.

Objective and hypotheses: We hypothesized that a lifestyle intervention in obese prepubertal children would result in differential metabolic signatures, in parallel to improvements in BMI. Our aim was to determine the changes in the urine and plasma metabolomics profiles induced by the intervention program.

Method: Longitudinal prospective study of obese (BMI>2SDS) prepubertal children ages 7–10. The lifestyle intervention was primarily educational, focused on children and family for 6 months. Untargeted metabolomics was applied to analyze urine (nuclear magnetic resonance) and plasma (liquid chromatography-mass spectrometry) samples to obtain a comprehensive metabolic profile at baseline and after intervention from 35 subjects.

Results: The intervention decreased BMI z-score (3.5±0.1 vs 3.1±0.1, P<0.001), waist-circumference (83.4±1.6 cm vs 81.6±1.6 cm, P<0.0019), and HbA1c levels (5.35±0.03% vs 5.22±0.03%, P<0.0004) using two-tails paired student t-test. Urine metabolomics identified 33 metabolites. Trimethylamineoxide (TMAO) levels, were significantly lower after intervention (0.72±0.19 vs 0.33±0.07, P=0.019). Plasma metabolomics identified 2566 features, and principal component analysis was applied to consolidate them into principal factors. Factor 1 differed between pre- and post-intervention (P<0.001, significance was maintained after adjusting for multiple comparisons); factor 1 was characterized by lipid metabolites, including triacylgycerols, diacylglycerols and ceramides.

Conclusion: A 6-month lifestyle intervention able to reduce BMI z-score changes the urine and plasma metabolome. In particular, the intervention reduced TMAO levels, a major cardiovascular risk factor, and a number of lipid metabolites, including proinflammatory signals. Together, these data suggest that the intervention improves the cardiovascular and metabolic risk profiles in prepubertal obese children.