Biomarkers of glycolysis and tricarboxylic acid (TCA) cycle in youth with and without obesity

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 is essential for elucidating the underlying mechanisms contributing to metabolic dysregulation in this population.Forty-eight adolescents and young adults aged 15-24 years had plasma obtained after a 12-hour 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-hour oral glucose tolerance test (OGTT).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. 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.随着儿童肥胖患病率的不断攀升，明确青年群体体脂过剩所带来的代谢后果至关重要。具体而言，探究肥胖青年群体糖酵解与三羧酸循环（tricarboxylic acid cycle, TCA循环）的变化，对于阐明该人群代谢紊乱的潜在机制具有关键意义。本研究纳入了48名15~24岁的青少年及青年人群，所有受试者均在12小时空腹状态下采集血浆，用于检测葡萄糖、胰岛素及三羧酸循环中间产物的水平，包括丙酮酸、乳酸、延胡索酸、苹果酸、α-酮戊二酸、顺/反乌头酸及异柠檬酸。此外，所有受试者均接受了肝脏质子密度脂肪分数（proton-density fat fraction, PDFF）检测及3小时口服葡萄糖耐量试验（oral glucose tolerance test, OGTT）。本研究共纳入19名非肥胖青年（体重指数（Body Mass Index, BMI）：21.5 ± 0.5 kg/m²）及29名肥胖青年（BMI：37.3 ± 1.7 kg/m²）。与非肥胖青年相比，肥胖青年的血浆乳酸水平显著升高（P=0.015），丙酮酸水平亦呈升高趋势但差异无统计学意义（P=0.096）；而血浆延胡索酸（P=0.022）、苹果酸（P=0.009）、顺/反乌头酸（P=0.03）及柠檬酸/异柠檬酸（P=0.012）水平均显著降低。肝脏质子密度脂肪分数（PDFF）与血浆乳酸水平呈显著正相关（r=0.46，P=0.027）。脂肪组织胰岛素抵抗与糖酵解生物标志物无显著关联。代谢组学分析结果显示，肥胖与非肥胖青少年及青年人群具有截然不同的代谢特征，提示肥胖青年的有氧葡萄糖利用速率更低，这可能参与了胰岛素抵抗、2型糖尿病及心血管疾病的发生发展。