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Human obese white adipose tissue sheds depot-specific extracellular vesicles and reveals candidate biomarkers for monitoring obesity and its comorbidities

  • Tamara Camino
    Affiliations
    Grupo Obesidómica, Área de Endocrinología, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain
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  • Nerea Lago-Baameiro
    Affiliations
    Grupo Obesidómica, Área de Endocrinología, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain
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  • Susana Belén Bravo
    Affiliations
    Unidad de Proteómica, Instituto de Investigación Sanitaria de Santiago (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain
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  • Alberto Molares-Vila
    Affiliations
    Bioinformatics Platform, Instituto de Investigación Sanitaria de Santiago (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain
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  • Aurelio Sueiro
    Affiliations
    Grupo Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Spain
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  • Iván Couto
    Affiliations
    Servicio de Cirugía Plástica y Reparadora, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain
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  • Javier Baltar
    Affiliations
    Grupo Obesidómica, Área de Endocrinología, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain

    Servicio de Cirugía General, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain
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  • Eelipe F Casanueva
    Affiliations
    Grupo Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Spain

    CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Spain
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  • Maria Pardo
    Correspondence
    Reprint requests: María Pardo, Grupo Obesidómica, Área de Endocrinología Lab # 3, Instituto de Investigaciones Sanitarias (IDIS), Xerencia da Xestión Integrada de Santiago (SERGAS), Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain.
    Affiliations
    Grupo Obesidómica, Área de Endocrinología, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), Santiago de Compostela, Spain

    CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Spain
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Published:January 16, 2021DOI:https://doi.org/10.1016/j.trsl.2021.01.006
      Extracellular vesicles (EVs) have been recently postulated as key players in metabolic disorders emerging as an alternative way of paracrine/endocrine communication. However, the nature of EVs shed by adipose tissue (AT) and their role in obesity is still very limited. Here, we isolated human morbid obese visceral (VAT) and subcutaneous (SAT) whole AT shed EVs from donors submitted to bariatric surgery to characterize their protein cargo by qualitative and quantitative/SWATH mass spectrometry analysis. We identified 574 different proteins shed by morbid obese VAT and 401 proteins in those from SAT, establishing the first obese AT EV proteome reference map. Only 50% of identified proteins in VAT vesicles were common to those in SAT; additionally, EVs shed by obese VAT showed more AT and obesity-related adipokines than SAT. Functional classification shows that obese VAT vesicles exhibit an enrichment of proteins implicated in AT inflammation and insulin resistance such as TGFBI, CAVN1, CD14, mimecan, thrombospondin-1, FABP-4 or AHNAK. Selected candidate biomarkers from the quantitative-SWATH analysis were validated in EVs from independent morbid obese and from moderate obese to lean individuals showing that morbid obese VAT vesicles are characterized by a diminution of syntenin 1 and the elevation of TGFBI and mimecan. Interestingly, TGFBI and mimecan containing vesicles could be detected and quantified at circulating level in plasma. Thus, a significant elevation of -TGFBI-EVs was detected on those obese patients with a history of T2D compared to nondiabetic, and an augmentation of mimecan-EVs in obese plasma compared to those in healthy lean individuals. Thus, we conclude that obese AT release functional EVs carrying AT and obesity candidate biomarkers which vary regarding the AT of origin. Our findings suggest that circulating EV-TGFBI may facilitate monitoring T2D status in obese patients, and EV-mimecan may be useful to track adiposity, and more precisely, visceral obesity.

      Abbreviations:

      EVs (extracellular vesicles), VAT (visceral adipose tissue), SAT (subcutaneous adipose tissue), AT (adipose tissue)
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