Time-course Effects of Increased Fatty Acid Supply on the Expression of Genes Involved in Lipid/Glucose Metabolism in Muscle Cells
Time-course Effects of Increased Fatty Acid Supply on the Expression of Genes Involved in Lipid/Glucose Metabolism in Muscle Cells
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增加脂肪酸供应对肌肉细胞脂质/葡萄糖代谢相关基因表达的时程影响
DOI：
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发表时间：
2010
影响因子：
--
通讯作者：
A. Palou
中科院分区：
文献类型：
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作者：
A. M. Rodríguez;Juana Sánchez;Aixa Tobaruela;T. Priego;C. Picó;A. Palou
骨骼肌中脂肪酸（FA）过量与肥胖相关的代谢紊乱以及正常的生理反应有关。我们在体内和体外研究了 FA 生理增加的时间反应，分析了对葡萄糖/脂质代谢重要的选定基因的表达。在雄性 Wistar 大鼠中使用禁食（已知会增加循环 FA）和重新喂养的体内连续模型来研究比目鱼肌（氧化性更强）和腓肠肌（糖酵解性更强）肌肉，并在生理浓度的油酸/亚油酸 FA 混合物处理下对 C2C12 肌肉细胞进行时间顺序研究。监测体重、肌糖原和血液参数（葡萄糖、胰岛素、游离脂肪酸-FFA-、甘油三酯）。肌肉肉毒碱棕榈酰转移酶 1 (mCPT1)、GLUT 4、胰岛素受体 (InsR)、MyoD1、过氧化物酶体增殖物激活受体 (PPAR) γ 共激活剂 1α (PGC1α) 和 β (PGC1β)、PPARα、PPARδ、丙酮酸脱氢酶激酶 4 (PDK4) 和解偶联蛋白 (UCP) 2 和 3 的 mRNA 水平通过定量 RT-PCR 进行分析。主要结果是在体内快速诱导PGC1α、UCP3和PDK4（在腓肠肌中更为明显）以及在体外快速诱导PGC1α、PGC1β、InsR、PDK4、UCP2和UCP3。结论是，FA能够快速诱导肌肉细胞中参与分解代谢的关键基因的表达，并且油酸/亚油酸混合物对增加主代谢调节因子及其下游靶基因的表达具有积极作用，促进从更多糖酵解代谢向更多脂质氧化代谢的转变。
Fatty acid (FA) oversupply in skeletal muscle is related with metabolic disorders associated to obesity, and also with normal physiological responses. We studied, in vivo and in vitro, the chronological response to physiological increases of FA, analyzing the expression of selected genes important for glucose/lipid metabolism. An in vivo sequential model of fasting (known to increase circulating FA) and refeeding was used in male Wistar rats to study soleus (more oxidative) and gastrocnemius (more glycolytic) muscles, and a chronological study was made in C2C12 muscle cells under treatment of oleic/linoleic FA mixture, at physiological concentration. Body weight, muscle glycogen and blood parameters (glucose, insulin, free fatty acids -FFA-, triglycerides) were monitored. mRNA levels of muscle carnitine palmitoyl transferase 1 (mCPT1), GLUT 4, insulin receptor (InsR), MyoD1, peroxisome proliferator activated receptor (PPAR) γ coactivator 1α (PGC1α) and β (PGC1β), PPARα, PPARδ, pyruvate dehydrogenase kinase 4 (PDK4) and uncoupling proteins (UCPs) 2 and 3 were analyzed by quantitative RT-PCR. The main results were the quick induction of PGC1α, UCP3 and PDK4 in vivo (more marked in gastrocnemius) and of PGC1α, PGC1β, InsR, PDK4, UCP2 and UCP3 in vitro. It is concluded that FA are able to rapidly induce the expression in muscle cells of key genes involved in their catabolism and that the oleic/linoleic acid mixture has a positive role increasing the expression of master metabolic regulators and their downstream target genes, facilitating the transition from a more glycolytic to a more lipid-oxidative metabolism.
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影响因子：
15.9
作者：
KELLEY, DE;MOKAN, M;MANDARINO, LJ
通讯作者：
MANDARINO, LJ
DOI：
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发表时间：
--
期刊：
--
影响因子：
--
作者：
G. Shulman;Howard
通讯作者：
G. Shulman;Howard
影响因子：
--
作者：
BARON, AD;BRECHTEL, G;EDELMAN, SV
通讯作者：
EDELMAN, SV
影响因子：
3.4
作者：
Muoio, Deborah M.;Koves, Timothy R.
通讯作者：
Koves, Timothy R.
影响因子：
29
作者：
Arany, Zoltan;Lebrasseur, Nathan;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.