Extracellular vesicles and inter-organ communication in cardiometabolic diseases

Soazig Le Lay

Investigator : Soazig Le Lay
Support staff : Josy-Anne Froger, Julie Magusto

Extracellular vesicles (EVs) characterize a heterogeneous set of membrane nanovesicles secreted by any kind of cells in the extracellular medium and circulating in the various fluids of the body. EVs convey biological material (proteins, lipids, nucleic acids, mitochondria) that they can transfer to target cells/tissues thus modulating their response and/or phenotype. The metabolic dysfunctions characterizing cardiometabolic diseases associated with obesity are associated with changes in circulating EV concentrations as well as alterations in their content.

The growing interest in EVs as new vectors of intercellular communication has led my group to question about their role in the development of obesity-associated metabolic complications. Part of my research’s activity takes place in Angers with local active collaboration with HIFIH/UPRES EA 3859 (Dir J.Boursier) on non-alcoholic steatohepatitis (NASH), reinforced by the FHU GO-NASH (coordinated by B.Cariou and J.Boursier).

Over the last decade, we actively contributed to demonstrate the involvement of EVs in adipose tissue pathophysiological remodeling processes associated with obesity. Particularly, we highlighted (i) the ability of Sonic Hedgehog-associated EVs to modulate adipocyte differentiation (Fleury et al, Sc Reports 2016), (ii) specific protein and lipid signatures of adipocyte-derived EV subtypes predictive of their metabolic responses (Durcin et al, JEV 2017), (iii) increased plasma EV concentrations with obesity, correlating with BMI and HOMA-IR, used as active secretion pathway of MIF cytokine (Amosse et al, Mol Metab 2018).
Our current program aims to study how adipose tissue-derived EVs participate to obesity-associated cardiometabolic complications development. To this purpose, the role of adipose EVs secreted in a lean or obesity context is investigated in pertinent cellular and murine preclinical models to assess and delineate their involvement in the development of cardiometabolic dysfunctions. The potential of EVs to serve as prognostic or diagnostic markers is moreover explored through circulating EV analysis in clinical cohorts displaying cardiometabolic diseases. Finally, a special effort is dedicated to EV functionalization (with industrial partnership), especially through a dedicated program aiming at using EVs as “molecular cabs” for adiponectin in the perspective to develop innovative EV-based anti-diabetic therapy.

Learn more about our projects

• Fondation Francophone pour la Recherche sur le Diabète (FFRD) : Soazig Le Lay (2023 - 2026)
• ANR EVADIPO : Soazig Le Lay (2022 - 2025)
• EVEXPONASH : Soazig Le Lay (2024 - 2027)

Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties. Blandin A, Amosse J, Froger J, Hilairet G, Durcin M, Fizanne L, Ghesquière V, Prieur X, Chaigneau J, Vergori L, Dray C, Pradère JP, Blandin S, Dupont J, Ducluzeau PH, Dubois S, Boursier J, Cariou B, Le Lay S. Cell Rep. 2023 Aug 29;42(8):112866. doi: 10.1016/j.celrep.2023.112866. Epub 2023 Aug 21.

Lipidomic analysis of adipose-derived extracellular vesicles reveals specific EV lipid sorting informative of the obesity metabolic state.Blandin A, Dugail I, Hilairet G, Ponnaiah M, Ghesquière V, Froger J, Ducheix S, Fizanne L, Boursier J, Cariou B, Lhomme M, Le Lay S. Cell Rep. 2023 Mar 28;42(3):112169. doi: 10.1016/j.celrep.2023.112169. Epub 2023 Mar 1.

Adipocyte-derived extracellular vesicles in health and diseases: Nano-packages with vast biological properties.Le Lay S, Rome S, Loyer X, Nieto L. FASEB Bioadv. 2021 Mar 4;3(6):407-419. doi: 10.1096/fba.2020-00147. eCollection 2021 Jun.

Phenotyping of circulating extracellular vesicles (EVs) in obesity identifies large EVs as functional conveyors of Macrophage Migration Inhibitory Factor. Amosse J, Durcin M, Malloci M, Vergori L, Fleury A, Gagnadoux F, Dubois S, Simard G, Boursier J, Hue O, Martinez MC, Andriantsitohaina R, Le Lay S. Mol Metab. 2018 Dec;18:134-142.

Characterisation of adipocyte-derived extracellular vesicle subtypes identifies distinct protein and lipid signatures for large and small extracellular vesicles. Durcin M, Fleury A, Taillebois E, Hilairet G, Krupova Z, Henry C, Truchet S, Trötzmüller M, Köfeler H, Mabilleau G, Hue O, Andriantsitohaina R, Martin P, Le Lay S. J Extracell Vesicles. 2017 Apr 10;6(1):1305677. doi: 10.1080/20013078.2017.1305677. eCollection 2017

This program has been supported by :

• Agence Nationale de la Recherche
• Fondation Francophone pour la Recherche sur le Diabète (FFRD)
• Société Francophone du Diabète
• Fédération Hospitalo-Universitaire, FHU GO-NASH
• Région Pays de la Loire
• EU FP7 « LipidomicNet »
• Genavie