Extracellular vesicles released by steatotic hepatocytes alter adipocyte metabolism
Authors
Mleczko, JE
Royo, F
Samuelson, I
Williams, C
Cabrera, D
Azparren‐Angulo, M
Gonzalez, E
Garcia‐Vallicrosa, C
Carobbio, S
Rodriguez‐Cuenca, S
Azkargorta, M
Liempd, S
Elortza, F
Vidal‐Puig, A
Mora, S
Publication Date
2022-02Journal Title
Journal of Extracellular Biology
ISSN
2768-2811
Publisher
Wiley
Volume
1
Issue
2
Language
en
Type
Article
This Version
AO
VoR
Metadata
Show full item recordCitation
Mleczko, J., Royo, F., Samuelson, I., Clos‐Garcia, M., Williams, C., Cabrera, D., Azparren‐Angulo, M., et al. (2022). Extracellular vesicles released by steatotic hepatocytes alter adipocyte metabolism. Journal of Extracellular Biology, 1 (2) https://doi.org/10.1002/jex2.32
Abstract
Abstract: The composition of extracellular vesicles (EVs) is altered in many pathological conditions, and their molecular content provides essential information on features of parent cells and mechanisms of crosstalk between cells and organs. Metabolic Syndrome (MetS) is a cluster of clinical manifestations including obesity, insulin resistance, dyslipidemia and hypertension that increases the risk of cardiovascular disease and type 2 diabetes mellitus. Here, we investigated the crosstalk between liver and adipocytes by characterizing EVs secreted by primary hepatocytes isolated from Zucker rat model, and studied the effect they have on 3T3‐L1 adipocytes. We found that steatotic hepatocytes secrete EVs with significantly reduced exosomal markers in comparison with their lean counterpart. Moreover, proteomic analysis revealed that those EVs reflect the metabolic state of the parent cell in that the majority of proteins upregulated relate to fat metabolism, fatty acid synthesis, glycolysis, and pentose phosphate pathway. In addition, hepatocytes‐secreted EVs influenced lipolysis and insulin sensitivity in recipient 3T3‐L1 adipocytes. Untargeted metabolomic analysis detected alterations in different adipocyte metabolic pathways in cells treated with hepatic EVs. In summary, our work showed that steatosis has a significant impact in the amount and composition of EVs secreted by hepatocytes. Moreover, our data point to the involvement of hepatic‐EVs in the development of pathologies associated with MetS.
Keywords
RESEARCH ARTICLE, RESEARCH ARTICLES, adipocytes, exosomes, extracellular vesicles, hepatocytes, inflammation, liver steatosis, metabolic syndrome, microvesicles, obesity, Zucker model
Sponsorship
Spanish Ministry of Science and Innovation (RTI2018‐094969‐B‐I00)
Identifiers
jex232
External DOI: https://doi.org/10.1002/jex2.32
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335006
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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