Poster Theater Flash Session
Energy and Macronutrient Metabolism
Objectives : To identify metabolites associated with BMIz and insulin resistance (IR) among 108 girls and 98 boys aged 8-14 years. We sought evidence of whether altered mitochondrial nutrient utilization, as indicated by mitochondrial-derived metabolites, mediates the relationship between diet, IR and obesity.
Methods : Anthropometry, fasting untargeted-liquid chromatography/mass spectrometry-derived metabolites and C-Peptide, and semi-quantitative food frequency questionnaires were collected from adolescents in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort. Sex-stratified generalized linear models were used to identify metabolites that are marginally associated BMIz and HOMA C-peptide (HOMA-CP), accounting for puberty, age and muscle and fat area (FDR < 0.1). Assessed the relationship between energy-adjusted macronutrient intake with HOMA-CP and BMIz. Structural equation models coupled with hierarchical clustering identified clusters of metabolites that may mediate the relationship between macronutrient intake with BMIz and HOMA-CP.
Results : Stratification by sex demonstrated sex-specific associations with BMIz. Most notable were girl’s positive association with diacylglycerols and boy’s positive association with branched chain and aromatic amino acids, independent of HOMA-CP. Intermediates in fatty acid metabolism, including medium chain acylcarnitines (acylCN), were inversely associated with HOMA-CP. No direct relationship was observed between macronutrient intake with BMIz and IR. Using mediation analyses, fat intake is positively associated with BMIz and HOMA-CP through increases in levels of dicarboxylic fatty acids (DiC-FA), products of omega-oxidation. Carbohydrate intake is positively associated with HOMA-CP through decreases in levels of medium chain acylCN, products of β-oxidation.
Conclusions : Insulin resistance in children appears to be associated with reduced fatty acid oxidation capacity. When consuming more grams of fat, there is evidence for increased extra-mitochondrial fatty acid metabolism (DiC-FA), while higher carbohydrate intake appears to lead to accumulation of intermediates of β-oxidation. Thus, biomarkers of IR and mitochondrial oxidative capacity may depend on macronutrient intake.
Funding Sources : This work was supported by the NIEHS, EPA and NIDDK