Preliminary evidence of glycine as a biomarker of cardiovascular disease risk in children with obesity.

Glycine (GLY) is a substrate for a wide range of metabolic processes. Several preclinical and adult studies demonstrated inverse associations of GLY with obesity, cardiovascular disease (CVD) and diabetes. However, little evidence is available on relationships between GLY and CVD risk in children. We assessed links between circulating GLY and biomarkers of CVD in children with obesity. Participants included both male and females with normal weight (NW, n = 6) and obesity (OB, n = 15), with age 14-18 years and Tanner stage >IV. Concentrations of GLY, branched chain amino acids (BCAA), and 25-hydroxy vitamin-D [25(OH)D], glucose, insulin, adiponectin, high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured using established techniques, and body composition by DXA. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Our study identified major relationships of GLY (p-value < 0.01 for all) of GLY with visceral fat (r2 = 0.40), BCAA (r2 = 0.44), HOMA-IR (r2 = 0.33), 25(OH)D (r2 = 0.48), IL-6 (r2 = 0.46) and adiponectin (r2 = 0.39). Given that CVD progression is a continuum and the disease itself is not present in children and biomarkers are typically used to monitor CVD in children, the links between GLY and biomarkers of CVD provide evidence for the first time of a potential role for GLY in CVD in children with obesity.

Branched-chain Amino Acids and Relationship With Inflammation in Youth With Obesity: A Randomized Controlled Intervention Study.

CONTEXT: Elevated concentrations of branched-chain amino acids (BCAA) are strong predictors of type 2 diabetes mellitus (T2DM). Their association with cardiovascular disease (CVD) remains uncertain, particularly in youth. OBJECTIVE: We investigated the role of BCAA and aromatic amino acids (AAA) in obesity, their relationships with novel biomarkers of CVD, and response to a physical activity-based lifestyle intervention (PAL-I) in a randomized controlled study in youth with normal weight (NW) and obesity (OB). METHODS: Age (14-18 years) and Tanner stage (≥IV) matched youth (OB, n = 15 and NW, n = 6) were studied; the 15 participants with OB underwent a 3-month randomized controlled PAL-I. Circulating amino acid profile, glucose, insulin, lipids, adiponectin, retinol binding protein-4, fibrinogen, high-sensitivity C-reactive protein, interleukin-6, and 25-hydroxy vitamin-D, along with body composition, were measured at baseline and after PAL-I. Independent t tests, analysis of covariance, and mixed-effect models were used for analysis of the data. RESULTS: Compared with NW, the concentration of various amino acids, including BCAA and AAA, were altered in OB (P < 0.05). BCAA and AAA showed baseline correlations with body composition and novel biomarkers of CVD, particularly inflammatory factors (all P < 0.05). The PAL-I produced only negligible effects (P > 0.05) on BCAA and AAA. Glutamine, glycine, and aspartic acid decreased with PAL-I (all P < 0.05). CONCLUSION: The novel finding of the BCAA-inflammation relationship, along with strong correlations with nontraditional biomarkers of CVD, may raise the prospect of BCAA as a biomarker of CVD and evoke a potential link between obesity, T2DM, and CVD.