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

Autor: Iván Couto, Tamara Camino, Aurelio M. Sueiro, Nerea Lago-Baameiro, Fernando Santos, María Pardo, Javier Baltar, Felipe F. Casanueva, Susana B. Bravo
Přispěvatelé: Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina
Rok vydání: 2020
Předmět:
Proteomics
0301 basic medicine
Lipid hypertrophy
Cell
Adipose tissue
lcsh:Chemistry
Mice
chemistry.chemical_compound
0302 clinical medicine
Transforming Growth Factor beta
insulin resistance
Lipid droplet
Adipocyte
Adipocytes
lcsh:QH301-705.5
lipid hypertrophy
Spectroscopy
Extracellular Matrix Proteins
Chemistry
Ceruloplasmin
General Medicine
Extracellular vesicles
Computer Science Applications
Cell biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
medicine.symptom
extracellular vesicles
SWATH
Perilipin-1
adipocytes
Inflammation
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
proteomics
Insulin resistance
Adipokines
medicine
Animals
Obesity
Physical and Theoretical Chemistry
Molecular Biology
Interleukin-6
Tumor Necrosis Factor-alpha
Organic Chemistry
Lipid Droplets
medicine.disease
RAW 264.7 Cells
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
inflammation
Zdroj: Minerva: Repositorio Institucional de la Universidad de Santiago de Compostela
Universidad de Santiago de Compostela (USC)
Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname
International Journal of Molecular Sciences
Volume 21
Issue 6
International Journal of Molecular Sciences, Vol 21, Iss 6, p 2252 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21062252
Popis: 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 TNF&alpha
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.
Databáze: OpenAIRE
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