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Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

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Grupo Obesidómica, Área de Endocrinología, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), 15706 Santiago de Compostela, Spain
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Unidad de Proteómica, Instituto de Investigación Sanitaria de Santiago (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), 15706 Santiago de Compostela, Spain
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Grupo Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), 15706 Santiago de Compostela, Spain
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CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, 15706 Santiago de Compostela, Spain
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Servicio de Cirugía Plástica y Reparadora, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), 15706 Santiago de Compostela, Spain
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Servicio de Cirugía General, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), 15706 Santiago de Compostela, Spain
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(6), 2252; https://doi.org/10.3390/ijms21062252
Received: 28 February 2020 / Revised: 17 March 2020 / Accepted: 19 March 2020 / Published: 24 March 2020
(This article belongs to the Section Molecular Endocrinology and Metabolism)
Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNFα expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established. View Full-Text
Keywords: extracellular vesicles; adipocytes; insulin resistance; lipid hypertrophy; inflammation; proteomics; SWATH extracellular vesicles; adipocytes; insulin resistance; lipid hypertrophy; inflammation; proteomics; SWATH
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MDPI and ACS Style

Tamara, C.; Nerea, L.-B.; Belén, B.S.; Aurelio, S.; Iván, C.; Fernando, S.; Javier, B.; Felipe, C.F.; María, P. Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes. Int. J. Mol. Sci. 2020, 21, 2252.

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