Biomarkers of Glycolysis and the Tricarboxylic Acid Cycle in Youth with and without Obesity

Introduction: Given the rising prevalence of childhood obesity, it is critical to understand the metabolic consequences of excess adiposity in youth. In particular, investigating alterations in glycolysis and the tricarboxylic acid (TCA) cycle in youth with obesity are essential for elucidating the underlying mechanisms contributing to metabolic dysregulation in this population. Methods: Forty-eight adolescents and young adults aged 15-24 years had plasma obtained after a 12-h fasting to measure levels of glucose, insulin, and TCA cycle intermediates: pyruvate, lactate, fumarate, malate, α-ketoglutarate, cis/trans aconitate, and isocitrate. Additionally, participants underwent an assessment of liver proton-density fat fraction (PDFF) and a 3-h oral glucose tolerance test (OGTT). Results: Nineteen youth without obesity (BMI 21.5 ± 0.5 kg/m2) and twenty-nine youth with obesity (BMI 37.3 ± 1.7 kg/m2) were enrolled in the study. Youth with obesity showed higher plasma concentrations of lactate (p = 0.015) and pyruvate (p = 0.096) and lower plasma concentrations of fumarate (p = 0.022), malate (p = 0.009), cis/trans aconitate (p = 0.03), and citrate/isocitrate (p = 0.012). PDFF was directly correlated with lactate (r = 0.46, p = 0.027). Adipose tissue insulin resistance was not associated with biomarkers of glycolysis. Conclusion: The metabolomic analysis revealed distinct characteristics between adolescents with and without obesity, thus demonstrating lower rates of aerobic glucose utilization in youth with obesity, which may contribute to the development of insulin resistance, type 2 diabetes, and cardiovascular disease.