Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36
Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36
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DOI：
10.1096/fj.03-1065fje
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发表时间：
2004-05-01
期刊：
影响因子：
4.8
通讯作者：
Dyck, DJ
中科院分区：
文献类型：
--
作者：
Bonen, A;Parolin, ML;Dyck, DJ
我们研究了在人类肥胖和 2 型糖尿病中，长链脂肪酸 (LCFA) 向骨骼肌的转运是否上调并导致肌内三酰甘油积累过多。在从人类骨骼肌制备的巨大肌膜囊泡中，LCFA 转运率上调了约 4 倍，并且与肥胖个体和 2 型糖尿病患者肌内三酰甘油含量增加相关。在这些个体中，肌膜 LCFA 转运率的增加与 FAT/CD36 或 FABPpm 表达的改变无关。相反，LCFA 转运率的增加与肌膜 FAT/CD36 的增加有关，但与肌膜 FABPpm 的增加无关。从肥胖受试者获得的分离的人体肌肉条中，脂肪酸酯化率增加了三倍，而同时脂肪酸氧化率没有改变。因此，脂肪酸转运速率的增加可能导致人体骨骼肌中三酰甘油积累速率的增加。肥胖受试者和 2 型糖尿病患者肌肉中 FAT/CD36 运输的改变与 GLUT4 运输中已知的改变并列，即已知 GLUT4 保留在其细胞内库中，而 FAT/CD36 保留在肌膜中。 FAT/CD36向肌膜的重新分布可能有助于人类肌肉胰岛素抵抗的病因学，因此，FAT/CD36为预防和/或治疗胰岛素抵抗提供了另一个潜在的治疗靶点。
We examined whether, in human obesity and type 2 diabetes, long chain fatty acid (LCFA) transport into skeletal muscle is upregulated and contributes to an excess intramuscular triacylglycerol accumulation. In giant sarcolemmal vesicles prepared from human skeletal muscle, LCFA transport rates were upregulated similar to4-fold and were associated with an increased intramuscular triacylglycerol content in obese individuals and in type 2 diabetics. In these individuals, the increased sarcolemmal LCFA transport rate was not associated with an altered expression of FAT/CD36 or FABPpm. Instead, the increase in the LCFA transport rate was associated with an increase in sarcolemmal FAT/CD36 but not sarcolemmal FABPpm. Rates of fatty acid esterification were increased threefold in isolated human muscle strips obtained from obese subjects, while concomitantly rates of fatty acid oxidation were not altered. Thus, the increased rate of fatty acid transport may contribute to the increased rates of triacylglycerol accumulation in human skeletal muscle. The altered FAT/CD36 trafficking in muscle from obese subjects and type 2 diabetics juxtaposes the known alterations in GLUT4 trafficking, i.e., GLUT4 is known to be retained in its intracellular depots while FAT/CD36 is retained at the sarcolemma. This redistribution of FAT/CD36 to the sarcolemma may contribute to the etiology of insulin resistance in human muscle, and hence, FAT/CD36 provides another potential therapeutic target for the prevention and/or treatment of insulin resistance.