DOI: 10.2337/db05-1322. 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

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

10.2337/db05-1322

Crossref journal-article

American Diabetes Association

Diabetes (1167)

Abstract

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 5′–AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK) are involved in the activation of peroxisome proliferator–activated receptor (PPAR)α by adiponectin in muscle cells. Adiponectin increases the transcriptional activity of PPARα 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 PPARα 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 PPARα.

Bibliography

Yoon, M. J., Lee, G. Y., Chung, J.-J., Ahn, Y. H., Hong, S. H., & Kim, J. B. (2006). Adiponectin Increases Fatty Acid Oxidation in Skeletal Muscle Cells by Sequential Activation of AMP-Activated Protein Kinase, p38 Mitogen-Activated Protein Kinase, and Peroxisome ProliferatorâActivated Receptor Î±. Diabetes, 55(9), 2562â2570.

Authors 6

Myeong Jin Yoon (first)
Gha Young Lee (additional)
Jun-Jae Chung (additional)
Young Ho Ahn (additional)
Seung Hwan Hong (additional)
Jae Bum Kim (additional)

References 47 Referenced 448

Dates

Type	When
Created	19 years ago (Aug. 25, 2006, 5:48 p.m.)
Deposited	2 years, 10 months ago (Nov. 2, 2022, 12:05 p.m.)
Indexed	6 days, 18 hours ago (Aug. 31, 2025, 7:28 p.m.)
Issued	19 years ago (Sept. 1, 2006)
Published	19 years ago (Sept. 1, 2006)
Published Print	19 years ago (Sept. 1, 2006)

Funders 0

None

BibTeX

@article{Yoon_2006, title={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}, volume={55}, ISSN={1939-327X}, url={http://dx.doi.org/10.2337/db05-1322}, DOI={10.2337/db05-1322}, number={9}, journal={Diabetes}, publisher={American Diabetes Association}, author={Yoon, Myeong Jin and Lee, Gha Young and Chung, Jun-Jae and Ahn, Young Ho and Hong, Seung Hwan and Kim, Jae Bum}, year={2006}, month=sep, pages={2562–2570} }

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  "abstract": "<jats:p>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 5\u2032\u2013AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK) are involved in the activation of peroxisome proliferator\u2013activated receptor (PPAR)\u03b1 by adiponectin in muscle cells. Adiponectin increases the transcriptional activity of PPAR\u03b1 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\u03b1 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\u03b1.</jats:p>",
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