Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 105, Issue 7, Pages 2442-2455Publisher
ENDOCRINE SOC
DOI: 10.1210/clinem/dgaa260
Keywords
metabolome; insulin resistance; BMI; adolescents; macronutrient; fatty acid oxidation
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Funding
- National Institute for Environmental Health Sciences [P20 ES018171, P01 ES022844]
- US Environmental Protection Agency [RD83543601]
- National Institutes of Health [R24 DK097153, P30 DK089503, U24 DK097153]
- Taubman Institute of the University of Michigan
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Context: A person's intrinsic metabolism, reflected in the metabolome, may describe the relationship between nutrient intake and metabolic health. Objectives: Untargeted metabolomics was used to identify metabolites associated with metabolic health. Path analysis classified how habitual dietary intake influences body mass index z-score (BMIz) and insulin resistance (IR) through changes in the metabolome. Design: Data on anthropometry, fasting metabolites, C-peptide, and dietary intake were collected from 108 girls and 98 boys aged 8 to 14 years. Sex-stratified linear regression identified metabolites associated with BMIz and homeostatic model assessment of IR using C-peptide (HOMA-CP), accounting for puberty, age, and muscle and fat area. Path analysis identified clusters of metabolites that underlie the relationship between energy-adjusted macronutrient intake with BMIz and HOMA-CP. Results: Metabolites associated with BMIz include positive associations with diglycerides among girls and positive associations with branched chain and aromatic amino acids in boys. Intermediates in fatty acid metabolism, including medium-chain acylcarnitines (AC), were inversely associated with HOMA-CP. Carbohydrate intake is positively associated with HOMA-CP through decreases in levels of AC, products of beta-oxidation. Approaching significance, fat intake is positively associated with HOMA-CP through increases in levels of dicarboxylic fatty acids, products of omega-oxidation. Conclusions: This cross-sectional analysis suggests that IR in children is associated with reduced fatty acid oxidation capacity. When consuming more grams of fat, there is evidence for increased extramitochondrial fatty acid metabolism, while higher carbohydrate intake appears to lead to decreases in intermediates of beta-oxidation. Thus, biomarkers of IR and mitochondrial oxidative capacity may depend on macronutrient intake.
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