title: Proteomic analysis of the palmitate-induced myotube secretome reveals involvement of the annexin A1-formyl peptide receptor 2 (FPR2) pathway in insulin resistance.
abstract: 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.
authors.affiliation: From the ‡Department of Life Sciences.
authors.forename: Jong Hyuk
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: From the ‡Department of Life Sciences.
authors.forename: Dayea
authors.initials: D
authors.lastname: Kim
authors.affiliation: §School of Interdisciplinary Bioscience and Bioengineering.
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Jang
authors.affiliation: From the ‡Department of Life Sciences.
authors.forename: Jaewang
authors.initials: J
authors.lastname: Ghim
authors.affiliation: From the ‡Department of Life Sciences.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Park
authors.affiliation: From the ‡Department of Life Sciences.
authors.forename: Parkyong
authors.initials: P
authors.lastname: Song
authors.affiliation: From the ‡Department of Life Sciences.
authors.forename: Yonghoon
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: ‖The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm SE-171 77, Sweden.
authors.forename: Jaeyoon
authors.initials: J
authors.lastname: Kim
authors.affiliation: §School of Interdisciplinary Bioscience and Bioengineering, ¶Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Kyungbuk 790-784, Republic of Korea, ‖‖Center for Plant Aging Research, Institute for Basic Science and Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 711-873, Republic of Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: **Department of Biological Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea, ‡‡Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, Republic of Korea.
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
authors.affiliation: §§School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, 689-798, Republic of Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.affiliation: ‖The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm SE-171 77, Sweden, Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 790-784, Republic of Korea.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.affiliation: From the ‡Department of Life Sciences, sungho@postech.ac.kr.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000819:agonists / Q000378:metabolism*; D002460:Cell Line; D019295:Computational Biology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D059305:Diet, High-Fat; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010168:Palmitates / Q000494:pharmacology*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000819:agonists* / Q000378:metabolism
chemical_list: D017305:Annexin A1; D017077:Culture Media, Conditioned; D007328:Insulin; D009842:Oligopeptides; D010168:Palmitates; D044042:Receptors, Formyl Peptide; C113617:Trp-Lys-Tyr-Met-Val-Met