Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Diabetes Care. 2012 Mar;35(3):605-11. doi: 10.2337/DC11-1577. Epub 2012 Jan 20.
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 [(2)H(5)]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.
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）青少年的酰基辅酶 A（AcylCN）种类、常见氨基酸和脂肪氧化（FOX）副产物以及血浆氨基酸。
采用串联质谱法分析空腹血浆，双能 X 射线吸收法和计算机断层扫描法分析身体成分，[(2)H5]甘油和间接测热法分别分析全身脂肪分解和底物氧化。通过 3 小时高胰岛素-正常血糖钳夹试验评估体内胰岛素敏感性（IS）。
三种人群的长链 AcylCN（C18:2-CN 至 C14:0-CN）相似。与 NW 相比，2 型糖尿病患者的中短链 AcylCN（除 C8 和 C10 外）明显降低，与 OB 相比，C2-、C6-和 C10-CN 降低。与 NW 相比，2 型糖尿病患者的氨基酸浓度较低。与 NW 相比，OB 和 2 型糖尿病患者的空腹脂肪分解和 FOX 较高，在控制肥胖、Tanner 分期和性别后，FOX 与 C10:1 的负相关关系消失。OB 和 2 型糖尿病患者的 IS 较低，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。
这些代谢组学结果以及体内 FOX 率的增加，不支持肥胖和青少年 2 型糖尿病患者的脂肪酸或氨基酸代谢缺陷。这些观察结果与青少年早期的适应性代谢可塑性一致，随着时间的推移——随着肥胖和衰老的持续——可能会变得功能失调，就像在成年人中观察到的那样。
