Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor α
Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor α
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DOI：
10.2337/db05-1322
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发表时间：
2006-09-01
期刊：
影响因子：
7.7
通讯作者：
Kim, Jae Bum
中科院分区：
文献类型：
--
作者：
Yoon, Myeong Jin;Lee, Gha Young;Kim, Jae Bum
脂联素由于其对胰岛素抵抗和代谢紊乱的有益作用而受到广泛关注。脂联素发挥这种作用的机制之一涉及肌肉和肝脏中脂肪酸氧化的增加。在本研究中，我们证明，W-AMP活化蛋白激酶（AMPK）和p38丝裂原活化蛋白激酶（MAPK）参与激活过氧化物酶体增殖物激活受体（PPAR）α的脂联素在肌肉细胞。脂联素增加C2 C12肌管中PPAR α的转录活性及其靶基因（包括ACO、CPT 1和FABP 3）的表达。这些影响被抑制的显性负性形式的AMPK的过度表达。此外，AMPK和p38 MAPK的化学抑制剂有效地抑制脂肪酸氧化和脂联素对PPAR α靶基因表达的诱导。有趣的是，AMPK抑制剂araA阻止了p38 MAPK的激活，而p38 MAPK抑制剂SB 203580不影响AMPK的激活，表明p38 MAPK是AMPK的下游信号传导因子。综上所述，这些结果表明，脂联素刺激肌肉细胞中的脂肪酸氧化的AMPK，p38 MAPK，和PPAR α的顺序激活。
Adiponectin has recently received a great deal of attention due to its beneficial effects on insulin resistance and metabolic disorders. One of the mechanisms through which adiponectin exerts such effects involves an increase in fatty acid oxidation in muscle and liver. In the present study, we demonstrate that W-AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK) are involved in the activation of peroxisome proliferator-activated receptor (PPAR)alpha by adiponectin in muscle cells. Adiponectin increases the transcriptional activity of PPAR alpha and the expression of its target genes, including ACO, CPT1, and FABP3 in C2C12 myotubes. These effects were suppressed by the overexpression of a dominant-negative form of AMPK. Moreover, chemical inhibitors of AMPK and p38 MAPK potently repressed fatty acid oxidation and the induction of PPAR alpha target gene expression by adiponectin. Interestingly, araA, an AMPK inhibitor, prevented the activation of p38 MAPK, whereas SB203580, a p38 MAPK inhibitor, did not affect AMPK activation, suggesting that p38 MAPK is a downstream signaling factor of AMPK. Taken together, these results suggest that adiponectin stimulates fatty acid oxidation in muscle cells by the sequential activation of AMPK, p38 MAPK, and PPAR alpha.