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2022-03-15

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cc-by (c) Mleczko, J.E. et al., 2022
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/184497

Extracellular vesicles released by steatotic hepatocytes alter adipocyte metabolism

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https://doi.org/10.1002/jex2.32

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.

Subject

Inflamació, Síndrome metabòlica, Obesitat

Subject (English)

Inflammation, Metabolic syndrome, Obesity

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

Citation

MLECZKO, J.E., et al. Extracellular vesicles released by steatotic hepatocytes alter adipocyte metabolism. Journal of Extracellular Biology. 2022. Vol. 1, num. 2, pags. e32. ISSN 2768-2811. [consulted: 18 of August of 2026]. Available at: https://hdl.handle.net/2445/184497

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