Increased intramyocellular lipid content but normal skeletal muscle mitochondrial oxidative capacity throughout the pathogenesis of type 2 diabetes
Increased intramyocellular lipid content but normal skeletal muscle mitochondrial oxidative capacity throughout the pathogenesis of type 2 diabetes
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DOI：
10.1096/fj.08-112318
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发表时间：
2008-11-01
期刊：
影响因子：
4.8
通讯作者：
Prompers, Jeanine J.
中科院分区：
文献类型：
--
作者：
De Feyter, Henk M.;Lenaers, Ellen;Prompers, Jeanine J.
目前遗传性或获得性骨骼肌线粒体功能障碍与脂肪酸代谢失调有关，导致肌细胞内脂质（IMCL）和脂质中间体水平升高，诱导胰岛素抵抗。本研究旨在阐明IMCL水平和骨骼肌线粒体功能在Zucker糖尿病脂肪（ZDF）大鼠2型糖尿病发展过程中的变化顺序。IMCL水平和骨骼肌氧化能力在体内测定，分别使用本地化H-1磁共振波谱（MRS）和动态P-31 MRS。同时，从参与脂肪酸氧化、三羧酸循环和电子传递链的酶测量体外活性。在对应于2型糖尿病的不同阶段的3个不同年龄研究Fa/fa ZDF大鼠，而fa/+大鼠作为对照。在整个研究期间，Fa/fa ZDF大鼠的IMCL含量高于对照组。在体内肌肉氧化能力是没有不同的FA/FA动物相比，对照组，在体外酶活性数据表明改善功能的酶参与脂肪氧化2型糖尿病动物。因此，我们可以得出结论，在ZDF大鼠模型中，2型糖尿病在没有骨骼肌线粒体功能障碍的情况下发展。- 德·费特M.，Lenaers，E.，Houten，S. M.，Schrauwen，P.，Hesselink，M. K.，万德斯河J.A.，Nicolay，K.，Prompers，J. J.在2型糖尿病的发病过程中，肌细胞内脂质含量增加，但骨骼肌线粒体氧化能力正常。FASEB J. 22，3947-3955（2008）
Currently inherited or acquired skeletal muscle mitochondrial dysfunction is linked to dysregulated fatty acid metabolism, resulting in increased levels of intramyocellular lipids (IMCLs) and lipid intermediates, inducing insulin resistance. The present study aimed to clarify the order of changes in IMCL levels and skeletal muscle mitochondrial function during the development of type 2 diabetes in Zucker diabetic fatty (ZDF) rats. IMCL levels and skeletal muscle oxidative capacity were determined in vivo, using localized H-1 magnetic resonance spectroscopy (MRS) and dynamic P-31 MRS, respectively. In parallel, in vitro activities were measured from enzymes involved in fatty acid oxidation, the tricarboxylic acid cycle and the electron transport chain. Fa/fa ZDF rats were studied at 3 different ages corresponding to different stages of type 2 diabetes, whereas fa/+ rats served as controls. Fa/fa ZDF rats had higher IMCL contents than controls throughout the duration of the study. In vivo muscle oxidative capacity was not different in fa/fa animals compared to controls, and in vitro enzyme activity data suggested improved functionality of enzymes involved in fat oxidation in type 2 diabetic animals. Accordingly, we can conclude that in the ZDF rat model, type 2 diabetes develops in the absence of skeletal muscle mitochondrial dysfunction. -De Feyter, H. M., Lenaers, E., Houten, S. M., Schrauwen, P., Hesselink, M. K., Wanders, R. J. A., Nicolay, K., Prompers, J. J. Increased intramyocellular lipid content but normal skeletal muscle mitochondrial oxidative capacity throughout the pathogenesis of type 2 diabetes. FASEB J. 22, 3947-3955 (2008)