Metabolomic profiling of fatty acid and amino acid metabolism in youth with obesity and type 2 diabetes: evidence for enhanced mitochondrial oxidation.
Metabolomic profiling of fatty acid and amino acid metabolism in youth with obesity and type 2 diabetes: evidence for enhanced mitochondrial oxidation.
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DOI：
10.2337/dc11-1577
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发表时间：
2012-03
期刊：
影响因子：
16.2
通讯作者：
Arslanian SA
中科院分区：
文献类型：
--
作者：
Mihalik SJ;Michaliszyn SF;de las Heras J;Bacha F;Lee S;Chace DH;DeJesus VR;Vockley J;Arslanian SA
我们比较了正常体重（NW, n = 39）、肥胖（OB, n = 64）和2型糖尿病（n = 17）青少年的酰基肉碱（AcylCN）种类、常见氨基酸和脂肪氧化（FOX）副产物以及血浆氨基酸。空腹血浆采用串联质谱法分析，体成分采用双能x线吸收仪和计算机断层扫描法分析，全身脂肪分解和底物氧化分别采用[2H5]甘油和间接量热法分析。体内胰岛素敏感性（IS）通过3小时高胰岛素-血糖钳夹进行评估。长链AcylCNs （C18:2-CN至C14:0-CN）在三组间相似。2型糖尿病中-短链AcylCNs（除C8和C10外）与NW相比显著降低，与OB相比，C2-， C6-和C10- cn均较低。与NW相比，2型糖尿病的氨基酸浓度较低。OB和2型糖尿病患者的空腹脂肪分解和FOX高于NW，在控制肥胖、Tanner分期和性别后，FOX与C10:1的负相关消失。OB和2型糖尿病患者的IS较低，在调整肥胖、Tanner分期和性别后，IS与精氨酸、组氨酸和丝氨酸呈正相关。这些代谢组学结果，加上体内FOX的增加率，不支持青少年肥胖和2型糖尿病中脂肪酸或氨基酸代谢缺陷的说法。这些观察结果与青少年早期的适应性代谢可塑性是一致的，随着时间的推移，随着持续的肥胖和衰老，可能会变得功能失调，正如在成年人中观察到的那样。
We compared acylcarnitine (AcylCN) species, common amino acid and fat oxidation (FOX) byproducts, and plasma amino acids in normal weight (NW; n = 39), obese (OB; n = 64), and type 2 diabetic (n = 17) adolescents. Fasting plasma was analyzed by tandem mass spectrometry, body composition by dual energy X-ray absorptiometry and computed tomography, and total-body lipolysis and substrate oxidation by [2H5]glycerol and indirect calorimetry, respectively. In vivo insulin sensitivity (IS) was assessed with a 3-h hyperinsulinemic-euglycemic clamp. Long-chain AcylCNs (C18:2-CN to C14:0-CN) were similar among the three groups. Medium- to short-chain AcylCNs (except C8 and C10) were significantly lower in type 2 diabetes compared with NW, and when compared with OB, C2-, C6-, and C10-CN were lower. Amino acid concentrations were lower in type 2 diabetes compared with NW. Fasting lipolysis and FOX were higher in OB and type 2 diabetes compared with NW, and the negative association of FOX to C10:1 disappeared after controlling for adiposity, Tanner stage, and sex. IS was lower in OB and type 2 diabetes with positive associations between IS and arginine, histidine, and serine after adjusting for adiposity, Tanner stage, and sex. These metabolomics results, together with the increased rates of in vivo FOX, are not supportive of defective fatty acid or amino acid metabolism in obesity and type 2 diabetes in youth. Such observations are consistent with early adaptive metabolic plasticity in youth, which over time—with continued obesity and aging—may become dysfunctional, as observed in adults.