Cited by 549Peroxisome Proliferator-Activated ReceptorsAdipose Tissue and MetabolismMetabolism, Diabetes, and Cancer

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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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Yoon, Myeong Jin, Lee, Gha Young, Chung, Jun-Jae, Ahn, Young Ho, Hong, Seung Hwan, Kim, Jae Bum·2006·Diabetes

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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)alpha by adiponectin in muscle cells. Adiponectin increases the transcriptional activity of PPARalpha 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 PPARalpha 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 PPARalpha.

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Authors: Yoon, M. J., Lee, G. Y., Chung, J.-J., Ahn, Y. H., Hong, S. H., & Kim, J. B.
Affiliations: Seoul National University (KR)
ORCID: Chung, Jun-Jae
Hong, Seung Hwan
Kim, Jae Bum
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2006-09-01
Volume: 55
Issue: 9
Pages: 2562-2570
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/db05-1322
OpenAlex: W2139409926
Cited by: 546
References: 48
Citations by year: 2026: 18 · 2025: 27 · 2024: 20 · 2023: 24 · 2022: 20 · 2021: 26 · 2020: 32 · 2019: 28 · 2018: 28 · 2017: 24 · 2016: 25 · 2015: 31 · 2014: 34 · 2013: 33 · 2012: 27
FWCI: 11.89
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: Ministry of Education and Human Resources Development
Directorate for Education and Human Resources
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: adiponectin, fatty acid oxidation, skeletal muscle, AMPK, p38 MAPK, PPARα, C2C12 myotubes, PPARα target genes, acetyl-CoA oxidase, carnitine palmitoyltransferase 1, fatty acid binding protein 3, insulin resistance
MeSH terms: Animals, Carnitine O-Palmitoyltransferase, Cells, Cultured, Enzyme Activation, Fatty Acids, Humans, Multienzyme Complexes, Oxidation-Reduction, Transcription, Genetic, Signal Transduction, Protein Serine-Threonine Kinases, Muscle, Skeletal, Acyl-CoA Oxidase, PPAR alpha, p38 Mitogen-Activated Protein Kinases, Mice, Adiponectin, AMP-Activated Protein Kinases

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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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