Proteomic Analysis of the Palmitate-induced Myotube Secretome Reveals Involvement of the Annexin A1-Formyl Peptide Receptor 2 (FPR2) Pathway in Insulin Resistance*

Yoon, Jong Hyuk; Kim, Dayea; Jang, Jin Hyeok; Ghim, Jaewang; Park, Soyeon; Song, Parkyong; Kwon, Yonghoon; Kim, Jaeyoon; Hwang, Daehee; Bae, Yoe Sik; Suh, Pann Ghill; Berggren, Per Olof; Ryu, Sung Ho

doi:10.1074/mcp.m114.039651

Cited by 40 publications

(44 citation statements)

References 45 publications

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“…gDetected in conditioned medium from murine muscle cells or explants cells with mass spectrometry analysis [13], [14], [15], [16], [20], [34], [35], [36].…”

Section: Figurementioning

confidence: 99%

“…In several proteomics studies, scientists have identified peptides in medium conditioned by cultured human [9], [10], [11], [12] or murine myocytes [13], [14], [15], [16]. To explain some of the positive effects of physical activity, several studies focused on identifying myokines that are elevated in response to exercise or muscle contraction [11], [17], [18], [19], [20].…”

Section: Introductionmentioning

confidence: 99%

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Global mRNA sequencing of human skeletal muscle: Search for novel exercise-regulated myokines

Pourteymour

Eckardt

Holen

et al. 2017

Molecular Metabolism

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ObjectiveSkeletal muscle is an important secretory organ, producing and releasing numerous myokines, which may be involved in mediating beneficial health effects of physical activity. More than 100 myokines have been identified by different proteomics approaches, but these techniques may not detect all myokines. We used mRNA sequencing as an untargeted approach to study gene expression of secreted proteins in skeletal muscle upon acute as well as long-term exercise.MethodsTwenty-six middle-aged, sedentary men underwent combined endurance and strength training for 12 weeks. Skeletal muscle biopsies from m. vastus lateralis and blood samples were taken before and after an acute bicycle test, performed at baseline as well as after 12 weeks of training intervention. We identified transcripts encoding secretory proteins that were changed more than 1.5-fold in muscle after exercise. Secretory proteins were defined based on either curated UniProt annotations or predictions made by multiple bioinformatics methods.ResultsThis approach led to the identification of 161 candidate secretory transcripts that were up-regulated after acute exercise and 99 that where increased after 12 weeks exercise training. Furthermore, 92 secretory transcripts were decreased after acute and/or long-term physical activity. From these responsive transcripts, we selected 17 candidate myokines sensitive to short- and/or long-term exercise that have not been described as myokines before. The expression of these transcripts was confirmed in primary human skeletal muscle cells during in vitro differentiation and electrical pulse stimulation (EPS). One of the candidates we identified was macrophage colony-stimulating factor-1 (CSF1), which influences macrophage homeostasis. CSF1 mRNA increased in skeletal muscle after acute and long-term exercise, which was accompanied by a rise in circulating CSF1 protein. In cultured muscle cells, EPS promoted a significant increase in the expression and secretion of CSF1.ConclusionWe identified 17 new, exercise-responsive transcripts encoding secretory proteins. We further identified CSF1 as a novel myokine, which is secreted from cultured muscle cells and up-regulated in muscle and plasma after acute exercise.

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“…gDetected in conditioned medium from murine muscle cells or explants cells with mass spectrometry analysis [13], [14], [15], [16], [20], [34], [35], [36].…”

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Global mRNA sequencing of human skeletal muscle: Search for novel exercise-regulated myokines

Pourteymour

Eckardt

Holen

et al. 2017

Molecular Metabolism

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“…More importantly, excess FFAs are implicated in the inhibition of pancreatic β-cell insulin secretory responsiveness and the induction of β-cell apoptosis [3]. Furthermore, the excess of saturated FFAs, such as palmitate (Palm), which induces lipotoxicity in primary human and mouse hepatocytes, have been implicated in insulin resistance in liver and muscle cells [4,5].…”

Section: Type 2 Diabetes Mellitus Is Characterized Bymentioning

confidence: 99%

Neutral ceramidase activity inhibition is involved in palmitate-induced apoptosis in INS-1 cells

Luo

Feng

et al. 2017

Endocr J

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Abstract. Neutral ceramidase (NCDase) is a class of ceramidases, a key enzyme in ceramide degradation. Recently, it was observed that NCDase activity was suppressed by saturated fatty acids to increase ceramide content in rat muscle. However, little is known about its changes in activity and roles in palmitate (Palm)-induced lipotoxicity in pancreatic β cells. Here, we demonstrated that Palm treatment significantly down-regulated NCDase activity, mRNA and protein levels in rat INS-1 cells. In addition, Palm caused a significant accumulation of ceramide, while SPH level remained unchanged, suggesting that inhibition of NCDase activity led to no change of SPH level after treatment with Palm for 24 h. Furthermore, NCDase overexpression significantly reduced Palm-induced apoptosis in INS-1 cells. Conversely, NCDase siRNA knockdown markedly exacerbated Palm-induced apoptosis. In conclusion, Palm treatment suppressed the activity of NCDase and down-regulated its mRNA and protein expression. Furthermore, NCDase inhibition was involved in Palm-induced apoptosis by blocking ceramide degradation in INS-1 cells.

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“…Chronic inflammation is also observed in obesity [68]. Interestingly, AnxA1 KO mice on a high-fat diet are 6 more prone to obesity than the control animals [69], and FPR2 activation improved systemic insulin sensitivity [70].…”

Section: Extracellular Functions-annexins As Ligands Of Defined Inflamentioning

confidence: 99%

Annexins in Translational Research: Hidden Treasures to be Found

Schloer

Pajonczyk

Rescher

2018

Preprint

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The vertebrate annexin superfamily (AnxA) consists of 12 calcium (Ca 2+ ) and phospholipid binding proteins which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca 2+ -controlled regulation of membrane events. In this review, we discuss several themes of potential therapeutic value, namely the regulation of the immune response and the control of tissue homeostasis, that repeatedly surface in the annexin action profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically clinical point of view.Preprints (www.preprints.org) | NOT PEER-REVIEWED |

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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*

Cited by 40 publications

References 45 publications

Global mRNA sequencing of human skeletal muscle: Search for novel exercise-regulated myokines

Global mRNA sequencing of human skeletal muscle: Search for novel exercise-regulated myokines

Neutral ceramidase activity inhibition is involved in palmitate-induced apoptosis in INS-1 cells

Annexins in Translational Research: Hidden Treasures to be Found

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