Plasmalemmal fatty acid transport is regulated in heart and skeletal muscle by contraction, insulin and leptin, and in obesity and diabetes
Plasmalemmal fatty acid transport is regulated in heart and skeletal muscle by contraction, insulin and leptin, and in obesity and diabetes
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DOI：
10.1046/j.1365-201x.2003.01157.x
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发表时间：
2003-08-01
期刊：
影响因子：
--
通讯作者：
Luiken, JJFP
中科院分区：
文献类型：
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作者：
Bonen, A;Benton, CR;Luiken, JJFP
长链脂肪酸被认为是通过被动扩散进入骨骼肌、心肌和其他组织的。近年来，我们的工作表明，LCFA摄取骨骼肌是一个高度调控的过程。利用从骨骼肌和心脏获得的巨大肌膜小泡，已经证明LCFA是通过涉及40 kDa质膜相关脂肪酸结合蛋白(FABPpm)和88 kDa脂肪酸转位酶(人类CD36(FAT/CD36)的同源物)的蛋白质介导机制被摄取到这些组织中的。两者都是普遍表达的蛋白质，与LCFA在心脏和肌肉中的摄取相关，这与这些组织中LCFA代谢的已知差异是一致的。最近发现，脂肪/CD36存在于细胞内(内体)室，通过肌肉收缩和胰岛素在几分钟内将其转运到质膜，从而刺激LCFA的摄取。在肥胖和1型糖尿病的啮齿动物模型中，心肌和肌肉对LCFA的摄取也增加，要么通过永久地将脂肪/CD36重新定位到质膜而不改变其表达(肥胖)，要么通过增加脂肪/CD36和FABPpm的表达(1型糖尿病)。慢性瘦素治疗减少了LCFA转运蛋白和肌肉中的转运。显然，最近的证据表明，LCFA在心脏和肌肉中的摄取受到尖锐和长期的调节。
It has been assumed that the uptake of long chain fatty acids (LCFAs) into skeletal muscle and the heart muscle, as well as other tissues, occurred via passive diffusion. In recent years our work has shown that the LCFA uptake into skeletal muscle is a highly regulated process. The use of giant sarcolemmal vesicles obtained from skeletal muscle and heart has been used to demonstrate that LCFA uptake into these tissues occurs via a protein-mediated mechanism involving the 40 kDa plasma membrane associated fatty acid binding protein (FABPpm) and the 88 kDa fatty acid translocase, the homologue of human CD36 (FAT/CD36). Both are ubiquitously expressed proteins and correlate with LCFA uptake into heart and muscle, consistent with the known differences in LCFA metabolism in these tissues. It has recently been found that FAT/CD36 is present in an intracellular (endosomal) compartment from which it can be translocated to the plasma membrane within minutes by muscle contraction and by insulin, to stimulate LCFA uptake. In rodent models of obesity and type 1 diabetes LCFA uptake into heart and muscle is also increased, either by permanently relocating FAT/CD36 to the plasma membrane without altering its expression (obesity) or by increasing the expression of both FAT/CD36 and FABPpm (type 1 diabetes). Chronic leptin treatment decreases LCFA transporters and transport in muscle. Clearly, recent evidence has established that LCFA uptake into heart and muscle is regulated acutely and chronically.