<b>Biomarkers of glycolysis and tricarboxylic acid (TCA) cycle in youth with and without obesity</b>

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.

鉴于儿童肥胖患病率持续攀升，阐明青少年体脂过多所带来的代谢影响至关重要。具体而言，针对肥胖青少年体内糖酵解与三羧酸循环（tricarboxylic acid cycle, TCA）的变化进行研究，对于阐明该人群代谢失调的潜在机制具有关键意义。本研究纳入48名15至24岁的青少年及青年群体，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、胰岛素以及TCA循环中间代谢物水平，包括丙酮酸、乳酸、延胡索酸、苹果酸、α-酮戊二酸、顺/反乌头酸以及异柠檬酸。此外，所有受试者还接受了肝脏质子密度脂肪分数（proton-density fat fraction, PDFF）检测以及3小时口服葡萄糖耐量试验（oral glucose tolerance test, OGTT）。本研究共纳入19名非肥胖青少年（体质指数（Body Mass Index, BMI）21.5 ± 0.5 kg/m²）以及29名肥胖青少年（BMI 37.3 ± 1.7 kg/m²）。与非肥胖青少年相比，肥胖青少年的血浆乳酸（P=0.015）与丙酮酸（P=0.096）水平更高，而血浆延胡索酸（P=0.022）、苹果酸（P=0.009）、顺/反乌头酸（P=0.03）以及柠檬酸/异柠檬酸（P=0.012）水平更低。肝脏质子密度脂肪分数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相关生物标志物并无关联。代谢组学分析结果显示，肥胖与非肥胖青少年具有截然不同的代谢特征，表明肥胖青少年的有氧葡萄糖利用效率更低，这或许会增加胰岛素抵抗、2型糖尿病以及心血管疾病的发病风险。