Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties

Alexia Blandin (1) , Jérémy Amosse (2, 3) , Josy Froger (4, 5) , Gregory Hilairet (4) , Maëva Durcin (4) , Lionel Fizanne (6, 7) , Valentine Ghesquière (4) , Xavier Prieur (5) , Julien Chaigneau (6, 7) , Luisa Vergori (4) , Cédric Dray (8) , Jean-Philippe Pradère (8) , Stéphanie Blandin (1) , Joëlle Dupont (9) , Pierre-Henri Ducluzeau (9) , Sèverine Dubois (6) , Jérôme Boursier (6, 7) , Bertrand Cariou (5) , Soazig Le Lay (4, 5)

1 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
2 Irset - Institut de recherche en santé, environnement et travail
3 EHESP - École des Hautes Études en Santé Publique [EHESP]
4 ICAT - SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques
5 ITX-lab - ITX-lab unité de recherche de l'institut du thorax UMR1087 UMR6291
6 CHU Angers - Centre Hospitalier Universitaire d'Angers
7 HIFIH - Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques
8 IBSV - Interactions Biotiques et Santé Végétale
9 PRC - Physiologie de la reproduction et des comportements [Nouzilly]

Recent evidence supporting that adipose tissue (AT)-derived extracellular vesicles (EVs) carry an important part of the AT secretome led us to characterize the EV-adipokine profile. In addition to evidencing a high AT-derived EV secretion ability that is further increased by obesity, we identify enrichment of oligomeric forms of adiponectin in small EVs (sEVs). This adipokine is mainly distributed at the EV external surface as a result of nonspecific adsorption of soluble adiponectin. EVs also constitute stable conveyors of adiponectin in the blood circulation. Adiponectin-enriched sEVs display in vitro insulin-sensitizing effects by binding to regular adiponectin receptors. Adoptive transfer of adiponectin-enriched sEVs in high-fat-diet-fed mice prevents animals from gaining weight and ameliorated insulin resistance and tissue inflammation, with major effects observed in the AT and liver. Our results therefore provide information regarding adiponectin-related metabolic responses by highlighting EVs as delivery platforms of metabolically active forms of adiponectin molecules.

Mots clés: CP: Metabolism; EVs; adipokines; adiponectin; adipose tissue; exosomes; extracellular vesicles; inflammtion; insulin resitance; obesity; type 2 diabetes

Domaines: Sciences du Vivant [q-bio]

Alexia Blandin, Jérémy Amosse, Josy Froger, Gregory Hilairet, Maëva Durcin, et al.. Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties. Cell Reports, 2023, 42 (8), pp.112866. ⟨10.1016/j.celrep.2023.112866⟩. ⟨hal-04198014⟩