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Proteomic Analysis of the Palmitate-induced Myotube Secretome Reveals Involvement of the Annexin A1-Formyl Peptide Receptor 2 (FPR2) Pathway in Insulin Resistance
- Proteomic Analysis of the Palmitate-induced Myotube Secretome Reveals Involvement of the Annexin A1-Formyl Peptide Receptor 2 (FPR2) Pathway in Insulin Resistance
- Yoon, JH[Yoon, Jong Hyuk]; Kim, D[Kim, Dayea]; Jang, JH[Jang, Jin-Hyeok]; Ghim, J[Ghim, Jaewang]; Park, S[Park, Soyeon]; Song, P[Song, Parkyong]; Kwon, Y[Kwon, Yonghoon]; Kim, J[Kim, Jaeyoon]; Hwang, D[Hwang, Daehee]; Bae, YS[Bae, Yoe-Sik]; Suh, PG[Suh, Pann-Ghill]; Berggren, PO[Berggren, Per-Olof]; Ryu, SH[Ryu, Sung Ho]
- DGIST Authors
- Hwang, D[Hwang, Daehee]
- Issue Date
- Molecular and Cellular Proteomics, 14(4), 882-892
- Article Type
- Agents Interacting With Transmitter, Hormone or Drug Receptors; Agonists; Animal; Animal Experiment; Animals; Annexin A1; Bioinformatics; Biology; C57Bl Mouse; Cell Adhesion; Cell Line; Cell Stress; Computational Biology; Conditioned Medium; Controlled Study; Culture Media, Conditioned; Diet, High-Fat; Drug Effects; Electrospray; Extracellular Matrix; Formyl Peptide Receptor 1; Formyl Peptide Receptor 2; Formyl Peptide Receptor 2 Agonist; Insulin; Insulin Resistance; Insulin Sensitivity; Interleukin-6; Lipid Diet; Lipocortin 1; Male; Metabolism; Mice, Inbred C57BL; Mouse; Mus; Muscle Fibers, Skeletal; Myotube; Non-Human; Oligopeptide; Oligopeptides; Palmitates; Palmitic Acid; Palmitic Acid Derivative; Pharmacology; Priority Journal; Procedures; Protein Expression; Protein Phosphorylation; Proteomics; Rat; Rats; Receptors, Formyl Peptide; Secretion (Process); Signal Transduction; Skeletal Muscle; Skeletal Muscle Cell; Treatment Outcome; Trp-Lys-Tyr-Met-Val-Met; Tumor Necrosis Factor-Alpha; Unclassified Drug; Western Blotting
- Elevated levels of the free fatty acid palmitate are found in the plasma of obese patients and induce insulin resistance. Skeletal muscle secretes myokines as extracellular signaling mediators in response to pathophysiological conditions. Here, we identified and characterized the skeletal muscle secretome in response to palmitate-induced insulin resistance. Using a quantitative proteomic approach, we identified 36 secretory proteins modulated by palmitate-induced insulin resistance. Bioinformatics analysis revealed that palmitate-induced insulin resistance induced cellular stress and modulated secretory events. We found that the decrease in the level of annexin A1, a secretory protein, depended on palmitate, and that annexin A1 and its receptor, formyl peptide receptor 2 agonist, played a protective role in the palmitate-induced insulin resistance of L6 myotubes through PKC-θ modulation. In mice fed with a high-fat diet, treatment with the formyl peptide receptor 2 agonist improved systemic insulin sensitivity. Thus, we identified myokine candidates modulated by palmitate-induced insulin resistance and found that the annexin A1-formyl peptide receptor 2 pathway mediated the insulin resistance of skeletal muscle, as well as systemic insulin sensitivity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
- American Society for Biochemistry and Molecular Biology Inc.
- Related Researcher
Hwang, Dae Hee
Systems Biology and Medicine Lab
Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
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