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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 ReceptorsAgonistsAnimalAnimal ExperimentAnimalsAnnexin A1BioinformaticsBiologyC57Bl MouseCell AdhesionCell LineCell StressComputational BiologyConditioned MediumControlled StudyCulture Media, ConditionedDiet, High-FatDrug EffectsElectrosprayExtracellular MatrixFormyl Peptide Receptor 1Formyl Peptide Receptor 2Formyl Peptide Receptor 2 AgonistInsulinInsulin ResistanceInsulin SensitivityInterleukin-6Lipid DietLipocortin 1MaleMetabolismMice, Inbred C57BLMouseMusMuscle Fibers, SkeletalMyotubeNon-HumanOligopeptideOligopeptidesPalmitatesPalmitic AcidPalmitic Acid DerivativePharmacologyPriority JournalProceduresProtein ExpressionProtein PhosphorylationProteomicsRatRatsReceptors, Formyl PeptideSecretion (Process)Signal TransductionSkeletal MuscleSkeletal Muscle CellTreatment OutcomeTrp-Lys-Tyr-Met-Val-MetTumor Necrosis Factor-AlphaUnclassified DrugWestern 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
  • Author Hwang, Daehee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
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Department of New BiologySystems Biology and Medicine Lab1. Journal Articles

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