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

被引:456
作者
Yoon, Myeong Jin
Lee, Gha Young
Chung, Jun-Jae
Ahn, Young Ho
Hong, Seung Hwan
Kim, Jae Bum
机构
[1] Seoul Natl Univ, Res Ctr Funct Cellulom, Dept Biol Sci, Lab Adipocyte & Metab Res, Seoul 151742, South Korea
[2] Seoul Natl Univ, Dept Biol Sci, Cell Biol Lab, Seoul 151, South Korea
关键词
ADIPOSE-SPECIFIC PROTEIN; INSULIN SENSITIVITY; PPAR-ALPHA; GLUCOSE-TRANSPORT; METABOLIC STRESS; DEFICIENT MICE; MALONYL-COA; GENE; OBESITY; PLASMA;
D O I
10.2337/db05-1322
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:2562 / 2570
页数:9
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