Rosiglitazone increases fatty acid oxidation and fatty acid translocase (FAT/CD36) but not carnitine palmitoyltransferase I in rat muscle mitochondria
Rosiglitazone increases fatty acid oxidation and fatty acid translocase (FAT/CD36) but not carnitine palmitoyltransferase I in rat muscle mitochondria
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DOI：
10.1113/jphysiol.2007.146563
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发表时间：
2008-03-15
影响因子：
5.5
通讯作者：
Bonen, Arend
中科院分区：
文献类型：
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作者：
Benton, Carley R.;Holloway, Graham P.;Bonen, Arend
过氧化物酶体增殖物激活受体（PPARs）改变参与调节脂质代谢的基因的表达。罗格列酮是一种PPAR γ激动剂，对脂质代谢具有组织特异性影响;然而，其在骨骼肌中的作用方式尚不清楚。由于脂肪酸移位酶（FAT/CD 36）最近被确定为骨骼肌脂肪酸转运和线粒体脂肪酸氧化的可能调节因子，我们在该组织中检查了罗格列酮输注（7天，1 mg/天（-1））对脂肪酸移位酶（FAT/CD 36）的影响mRNA和蛋白质、其质膜含量和脂肪酸转运。此外，在分离的肌膜下（SS）和肌原纤维间（IMF）线粒体，我们检查了脂肪酸氧化率，FAT/CD 36和肉毒碱棕榈酰转移酶I（CPTI）蛋白，和CPTI和β-羟酰辅酶A脱氢酶（β-HAD）的活动。罗格列酮对FAT/CD 36 mRNA、蛋白表达、细胞膜含量及脂肪酸转运率无明显影响（P > 0.05）。相反，罗格列酮增加了SS（+21%）和IMF线粒体（+36%）中的脂肪酸氧化速率。这伴随着肌膜下（SS）（+43%）和肌原纤维间（IMF）线粒体（+46%）中FAT/CD 36的增加，而SS和IMF CPTI蛋白含量以及CPTI次最大和最大活性（P > 0.05）没有改变。同样，罗格列酮也不影响SS和IMF线粒体中柠檬酸合酶（CS）和β-HAD活性（P > 0.05）。这些研究提供了另一个例子，其中线粒体脂肪氧化的变化与线粒体FAT/CD 36的伴随变化相关，而不依赖于CPTI的任何变化。此外，这些研究首次确定了罗格列酮刺激骨骼肌脂肪酸氧化的机制，即FAT/CD 36向线粒体的慢性亚细胞迁移。
Peroxisome proliferator-activated receptors (PPARs) alter the expression of genes involved in regulating lipid metabolism. Rosiglitazone, a PPAR gamma agonist, induces tissue-specific effects on lipid metabolism; however, its mode of action in skeletal muscle remains unclear. Since fatty acid translocase (FAT/CD36) was recently identified as a possible regulator of skeletal muscle fatty acid transport and mitochondrial fatty acid oxidation, we examined in this tissue the effects of rosiglitazone infusion (7 days, 1 mg day(-1)) on FAT/CD36 mRNA and protein, its plasmalemmal content and fatty acid transport. In addition, in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria we examined rates of fatty acid oxidation, FAT/CD36 and carnitine palmitoyltransferase I (CPTI) protein, and CPTI and beta-hydroxyacyl CoA dehydrogenase (beta-HAD) activities. Rosiglitazone did not alter FAT/CD36 mRNA or protein expression, FAT/CD36 plasmalemmal content, or the rate of fatty acid transport into muscle (P > 0.05). In contrast, rosiglitazone increased the rates of fatty acid oxidation in both SS (+21%) and IMF mitochondria (+36%). This was accompanied by concomitant increases in FAT/CD36 in subsarcolemmal (SS) (+43%) and intermyofibrillar (IMF) mitochondria (+46%), while SS and IMF CPTI protein content, and CPTI submaximal and maximal activities (P > 0.05) were not altered. Similarly, citrate synthase (CS) and beta-HAD activities were also not altered by rosiglitazone in SS and IMF mitochondria (P > 0.05). These studies provide another example whereby changes in mitochondrial fatty oxidation are associated with concomitant changes in mitochondrial FAT/CD36 independent of any changes in CPTI. Moreover, these studies identify for the first time a mechanism by which rosiglitazone stimulates fatty acid oxidation in skeletal muscle, namely the chronic, subcellular relocation of FAT/CD36 to mitochondria.