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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
Open accessAbstract
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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“By this mechanism, ApN increases the transcriptional activity of PPARα and the expression of its target genes, implicated in fatty-acid transport into the mitochondria (carnitine palmitoyltransferase 1, CPT1) and oxidation (Acyl-CoA Oxidase, ACO) [44] (Figure 2).”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [44]
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“AMPK is also implicated in the sequential activation of p38 mitogen-activated protein kinase (MAPK) and PPARα [44] (Figure 2).”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [44]
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“This translocation results from stimulating p38 MAPK via either AMPK [10,44] or interaction with APPL1 [55].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [44]
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Paradoxical Decrease of an Adipose-Specific Protein, Adiponectin, in Obesity
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A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes
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Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
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Plasma Concentrations of a Novel, Adipose-Specific Protein, Adiponectin, in Type 2 Diabetic Patients
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Adiponectin and Adiponectin Receptors
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The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
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AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity
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Novel Modulator for Endothelial Adhesion Molecules
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Pawlak, M., Lefebvre, P., & Staels, B. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2014.10.039 · Cited by 1,578
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Metadata
- Authors
- Yoon, M. J., Lee, G. Y., Chung, J.-J., Ahn, Y. H., Hong, S. H., & Kim, J. B.
- Affiliations
- Seoul National University (KR)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2006-09-01
- Volume
- 55
- Issue
- 9
- Pages
- 2562-2570
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- 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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