Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity.
Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity.
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DOI：
10.1038/oby.2009.510
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发表时间：
2010-09
期刊：
影响因子：
6.9
通讯作者：
DeLany, James P.
中科院分区：
文献类型：
--
作者：
Mihalik, Stephanie J.;Goodpaster, Bret H.;Kelley, David E.;Chace, Donald H.;Vockley, Jerry;Toledo, Frederico G. S.;DeLany, James P.
脂肪酸氧化失调（FAO）被认为是肥胖和胰岛素抵抗（IR）的重要病理生理学。然而，在人体内证明FAO缺陷需要复杂和侵入性的方法。最近，在粮农组织的遗传块的识别已大大简化，通过使用串联质谱（MS/MS）的干血斑，以指定酰基肉毒碱（AcylCN）的变化特征的每种疾病。该技术最近已被应用于研究肥胖和2型糖尿病（T2 DM）的人类和动物模型中的FAO改变。本研究的重点是表征空腹和胰岛素刺激条件下肥胖和T2 DM个体的人血浆中的AcylCN谱。禁食过夜后，从瘦型（n = 12）、肥胖型非糖尿病（n = 14）和T2 DM（n = 10）参与者中获得血浆，并使用MS/MS分析AcylCN。还在4小时胰岛素刺激的正葡萄糖钳夹结束时获得血浆样品。在肥胖症和2型糖尿病患者中，长链酰基氯化萘在空腹状态下也同样显著增加;游离氯化萘水平也有所升高。此外，BMI相当的T2 DM受试者的短链和中链酰基氯化萘（饱和和羟基）增加，C4-二羧基肉碱（C4 DC-CN）增加，这与血糖控制不良指数相关（HbA 1c; r = 0.74; P < 0.0001）。胰岛素输注降低了所有种类的血浆AcylCN，但这种降低在T2 DM中减弱。肥胖和T2 DM患者血浆长链AcylCN种类增加，表明更多脂肪酸可进入线粒体。在T2 DM中，许多较短的物质积累，表明它们具有普遍的复杂氧化缺陷。
Dysregulation of fatty acid oxidation (FAO) is recognized as important in the pathophysiology of obesity and insulin resistance (IR). However, demonstrating FAO defects in vivo in humans has entailed complex and invasive methodologies. Recently, the identification of genetic blocks in FAO has been vastly simplified by using tandem mass spectrometry (MS/MS) of dried bloodspots to specify acylcarnitine (AcylCN) alterations characteristic for each disorder. This technology has recently been applied to examine FAO alterations in human and animal models of obesity and type 2 diabetes mellitus (T2DM). This study focused on characterizing AcylCN profiles in human plasma from individuals with obesity and T2DM during fasting and insulin-stimulated conditions. Following an overnight fast, plasma was obtained from lean (n = 12), obese nondiabetic (n = 14), and T2DM (n = 10) participants and analyzed for AcylCN using MS/MS. Plasma samples were also obtained at the end of a 4-h insulin-stimulated euglycemic clamp. In obesity and T2DM, long-chain AcylCNs were similarly significantly increased in the fasted state; free-CN levels were also elevated. Additionally, T2DM subjects of comparable BMI had increased short- and medium-chain AcylCNs, both saturated and hydroxy, as well as increased C4-dicarboxylcarnitine (C4DC–CN) that correlated with an index of poor glycemic control (HbA1c; r = 0.74; P < 0.0001). Insulin infusion reduced all species of plasma AcylCN but this reduction was blunted in T2DM. Plasma long-chain AcylCN species are increased in obesity and T2DM, suggesting that more fatty acids can enter mitochondria. In T2DM, many shorter species accumulate, suggesting that they have a generalized complex oxidation defect.
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影响因子：
7.7
作者：
Toledo, Frederico G. S.;Menshikova, Elizabeta V.;Kelley, David E.
通讯作者：
Kelley, David E.
影响因子：
3.9
作者：
Cnop, Miriam;Igoillo-Esteve, Mariana;Eizirik, Decio L.
通讯作者：
Eizirik, Decio L.
影响因子：
7.7
作者：
Ritov, VB;Menshikova, EV;Kelley, DE
通讯作者：
Kelley, DE
DOI：
10.1016/0005-2760(83)90064-4
发表时间：
1983-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
VEERKAMP, JH;VANMOERKERK, HTB;VANHINSBERGH, VWM
通讯作者：
VANHINSBERGH, VWM
影响因子：
7.7
作者：
Prentki, M;Joly, E;Roduit, R
通讯作者：
Roduit, R