Association of Whole Blood Amino Acid and Acylcarnitine Metabolome with Anthropometry and IGF-I Serum Levels in Healthy Children and Adolescents in Germany

Abstract

Background: Physiological changes of blood amino acids and acylcarnitines during healthy child development are poorly studied. The LIFE (Leipziger Forschungszentrum für Zivilisationserkrankungen) Child study offers a platform with a large cohort of healthy children to investigate these dynamics. We aimed to assess the intra-person variability of 28 blood metabolites and their associations with anthropometric parameters related to growth and excess body fat.

Methods: Concentrations of 22 amino acids (AA), 5 acylcarnitines (AC) and free carnitine of 2213 children aged between 3 months and 19 years were analyzed using liquid chromatography/tandem mass spectrometry. Values were transformed into standard deviation scores (SDS) to account for sex- and age-related variations. The stability of metabolites was assessed through the coefficient of determination. Associations with parameters for body composition and insulin-like growth factor-I (IGF-I) SDS were determined by the Pearson correlation and linear regression.

Results: Our research revealed substantial within-person variation in metabolite concentrations during childhood and adolescence. Most metabolites showed a positive correlation with body composition parameters, with a notable influence of sex, pubertal status and weight group. Glycine exhibited negative associations with parameters of body fat distribution, especially in normal weight girls, overweight/obese boys and during puberty.

Conclusion: Blood AA and AC measurements may contribute to elucidating pathogenesis pathways of adiposity-related comorbidities, but the specific timings and conditions of development during childhood and adolescence need to be taken into consideration.

Keywords: acylcarnitines; amino acids; anthropometry; body composition; metabolomics; pediatrics.

Figure 1

Linear trends of year-to-year correlations of the consecutive metabolite concentration SDS across age for aromatic AAs (a) his = histidine, phe = phenylalanine, trp = tryptophan, tyr = tyrosine and ACs (b) c0 = free carnitine, c2 = acetylcarnitine, c3 = propionylcarnitine, c16 = palmitoylcarnitine, c18 = stearoylcarnitine, mma = methylmalonyl carnitine.

Figure 2

Heatmap showing Pearson correlation values (blue = positive, yellow = negative) between selected metabolite concentrations and anthropometric parameters in female and male children and adolescents (sf = skinfold, WHR = waist-to-hip ratio, BMI = body mass index).

Figure 3

Linear regression models showing the association between anthropometric parameters and mean SDS levels of proline; proline had a stronger positive association with anthropometric parameters in females.

Figure 4

Linear regression models showing the relationship between anthropometric parameters and mean SDS levels of C3. Male individuals showed a stronger association, particularly in the biceps and iliac crest skinfold as well as in BMI and waist circumference.

Figure 5

Heatmaps showing Pearson correlations (blue = positive, yellow = negative) between selected metabolite concentrations and anthropometric parameters in female (a) and male (b) children and adolescents (sf = skinfold thickness, WHR = waist-to-hip ratio, BMI = body mass index). The group designated overweight includes both individuals with overweight and obesity (BMI SDS < 1.28).

Figure 5

Heatmaps showing Pearson correlations (blue = positive, yellow = negative) between selected metabolite concentrations and anthropometric parameters in female (a) and male (b) children and adolescents (sf = skinfold thickness, WHR = waist-to-hip ratio, BMI = body mass index). The group designated overweight includes both individuals with overweight and obesity (BMI SDS < 1.28).