Mansell Toby, Magnussen Costan G, Nuotio Joel, Laitinen Tomi T, Harcourt Brooke E, Bekkering Siroon, McCallum Zoe, Kao Kung-Ting, Sabin Matthew A, Juonala Markus, Saffery Richard, Burgner David, Saner Christoph
Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC, Australia.
Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
Int J Obes (Lond). 2022 Mar;46(3):646-654. doi: 10.1038/s41366-021-01034-7. Epub 2022 Jan 6.
Obesity in childhood is associated with metabolic dysfunction, adverse subclinical cardiovascular phenotypes and adult cardiovascular disease. Longitudinal studies of youth with obesity investigating changes in severity of obesity with metabolomic profiles are sparse. We investigated associations between (i) baseline body mass index (BMI) and follow-up metabolomic profiles; (ii) change in BMI with follow-up metabolomic profiles; and (iii) change in BMI with change in metabolomic profiles (mean interval 5.5 years).
Participants (n = 98, 52% males) were recruited from the Childhood Overweight Biorepository of Australia study. At baseline and follow-up, BMI and the % >95th BMI-centile (percentage above the age-, and sex-specific 95th BMI-centile) indicate severity of obesity, and nuclear magnetic resonance spectroscopy profiling of 72 metabolites/ratios, log-transformed and scaled to standard deviations (SD), was performed in fasting serum. Fully adjusted linear regression analyses were performed.
Mean (SD) age and % >95th BMI-centile were 10.3 (SD 3.5) years and 134.6% (19.0) at baseline, 15.8 (3.7) years and 130.7% (26.2) at follow-up. Change in BMI over time, but not baseline BMI, was associated with metabolites at follow-up. Each unit (kg/m) decrease in sex- and age-adjusted BMI was associated with change (SD; 95% CI; p value) in metabolites of: alanine (-0.07; -0.11 to -0.04; p < 0.001), phenylalanine (-0.07; -0.10 to -0.04; p < 0.001), tyrosine (-0.07; -0.10 to -0.04; p < 0.001), glycoprotein acetyls (-0.06; -0.09 to -0.04; p < 0.001), degree of fatty acid unsaturation (0.06; 0.02 to 0.10; p = 0.003), monounsaturated fatty acids (-0.04; -0.07 to -0.01; p = 0.004), ratio of ApoB/ApoA1 (-0.05; -0.07 to -0.02; p = 0.001), VLDL-cholesterol (-0.04; -0.06 to -0.01; p = 0.01), HDL cholesterol (0.05; 0.08 to 0.1; p = 0.01), pyruvate (-0.08; -0.11 to -0.04; p < 0.001), acetoacetate (0.07; 0.02 to 0.11; p = 0.005) and 3-hydroxybuturate (0.07; 0.02 to 0.11; p = 0.01). Results using the % >95th BMI-centile were largely consistent with age- and sex-adjusted BMI measures.
In children and young adults with obesity, decreasing the severity of obesity was associated with changes in metabolomic profiles consistent with lower cardiovascular and metabolic disease risk in adults.
儿童肥胖与代谢功能障碍、不良亚临床心血管表型及成人心血管疾病相关。对肥胖青少年进行的纵向研究，调查肥胖严重程度与代谢组学特征变化的情况较为稀少。我们研究了以下几方面的关联：（i）基线体重指数（BMI）与随访代谢组学特征；（ii）BMI变化与随访代谢组学特征；（iii）BMI变化与代谢组学特征变化（平均间隔5.5年）。
参与者（n = 98，52%为男性）来自澳大利亚儿童超重生物样本库研究。在基线和随访时，BMI及BMI百分位数>95%（高于年龄和性别特异性BMI百分位数第95位的百分比）表明肥胖严重程度，并对空腹血清进行72种代谢物/比值的核磁共振波谱分析，进行对数转换并按标准差（SD）进行标准化。进行了完全调整的线性回归分析。
平均（SD）年龄及BMI百分位数>95%在基线时分别为10.3（SD 3.5）岁和134.6%（19.0），随访时分别为15.8（3.7）岁和130.7%（26.2）。随时间变化的BMI改变而非基线BMI与随访时的代谢物相关。经性别和年龄调整的BMI每降低1个单位（kg/m），与以下代谢物的变化（SD；95%置信区间；p值）相关：丙氨酸（-0.07；-0.11至-0.04；p < 0.001）、苯丙氨酸（-0.07；-0.10至-0.04；p < 0.001）、酪氨酸（-0.07；-0.10至-0.04；p < 0.001）、糖蛋白乙酰化物（-0.06；-0.09至-0.04；p < 0.001）、脂肪酸不饱和度程度（0.06；0.02至0.10；p = 0.003）、单不饱和脂肪酸（-0.04；-0.07至-0.01；p = 0.004）、载脂蛋白B/载脂蛋白A1比值（-0.05；-0.07至-0.02；p = 0.001）、极低密度脂蛋白胆固醇（-0.04；-0.06至-0.01；p = 0.01）、高密度脂蛋白胆固醇（0.05；0.08至0.1；p = 0.01）、丙酮酸（-0.08；-0.11至-0.04；p < 0.001）、乙酰乙酸（0.07；0.02至0.11；p = 0.005）和3-羟基丁酸（0.07；0.02至0.11；p = 0.01）。使用BMI百分位数>95%的结果与经年龄和性别调整的BMI测量结果基本一致。
在肥胖儿童和青年中，肥胖严重程度降低与代谢组学特征变化相关，这些变化与成人较低的心血管和代谢疾病风险一致。
