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

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.

Lipidomic analysis of adipose-derived extracellular vesicles reveals specific EV lipid sorting informative of the obesity metabolic state.

Adipose extracellular vesicles (AdEVs) transport lipids that could participate in the development of obesity-related metabolic dysfunctions. This study aims to define mouse AdEV lipid signature by a targeted LC-MS/MS approach in either healthy or obesity context. Distinct clustering of AdEV and visceral adipose tissue (VAT) lipidomes by principal component analysis reveals specific AdEV lipid sorting when compared with secreting VAT. Comprehensive analysis identifies enrichment of ceramides, sphingomyelins, and phosphatidylglycerols species in AdEVs compared with source VAT whose lipid content closely relates to the obesity status and is influenced by the diet. Obesity moreover impacts AdEV lipidome, mirroring lipid alterations retrieved in plasma and VAT. Overall, our study identifies specific lipid fingerprints for plasma, VAT, and AdEVs that are informative of the metabolic status. Lipid species enriched in AdEVs in the obesity context may constitute biomarker candidates or mediators of the obesity-associated metabolic dysfunctions.

[Extracellular vesicles and metabolic diseases: Dangerous liaisons]. / Vésicules extracellulaires et maladies métaboliques - Des liaisons dangereuses.

Extracellular vesicles (EVs) correspond to a heterogeneous set of membrane nanovesicles secreted in the extracellular medium and circulating in the various fluids of the body. These EVs convey biological material (proteins, lipids, nucleic acids) that they can transfer to target cells/tissues thus modulating their response and/or phenotype. The metabolic dysfunctions characterizing metabolic 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 to question about their role in the development of metabolic complications. In this review, we will discuss the literature on circulating EVs as potential markers of metabolic diseases and then detail inter-organ dialogue based on this EV trafficking underlying the development of related obesity. Finally, we will discuss future avenues of research that will help to better understand the link between EVs and metabolic diseases.

TITLE: Vésicules extracellulaires et maladies métaboliques - Des liaisons dangereuses. ABSTRACT: Les vésicules extracellulaires (VE) correspondent à un ensemble hétérogène de nanovésicules membranaires sécrétées dans le milieu extracellulaire et circulant dans les différents fluides de l'organisme. Ces VE véhiculent du matériel biologique (protéines, lipides, acides nucléiques) qu'elles peuvent transférer à des cellules/tissus cibles, modulant ainsi leur réponse et/ou leur phénotype. Les dysfonctions caractérisant les maladies métaboliques liées à l'obésité sont associées à des modifications des concentrations circulantes de VE ainsi qu'à des altérations de leur contenu. L'intérêt grandissant porté aux VE comme nouveaux vecteurs de communication intercellulaire a conduit à s'interroger sur leur rôle dans le développement des complications métaboliques. Dans cette synthèse, nous résumerons la littérature portant sur les VE circulantes comme potentiels marqueurs des maladies métaboliques. Nous détaillerons ensuite le dialogue vésiculaire inter-organes responsable du développement des complications associées à l'obésité. Enfin, nous discuterons les futures pistes de recherche qui contribueront à mieux appréhender le lien entre VE et maladies métaboliques.

Adipocyte-Derived Extracellular Vesicles: State of the Art.

White adipose tissue (WAT) is involved in long-term energy storage and represents 10-15% of total body weight in healthy humans. WAT secretes many peptides (adipokines), hormones and steroids involved in its homeostatic role, especially in carbohydrate-lipid metabolism regulation. Recently, adipocyte-derived extracellular vesicles (AdEVs) have been highlighted as important actors of intercellular communication that participate in metabolic responses to control energy flux and immune response. In this review, we focus on the role of AdEVs in the cross-talks between the different cellular types composing WAT with regard to their contribution to WAT homeostasis and metabolic complications development. We also discuss the AdEV cargoes (proteins, lipids, RNAs) which may explain AdEV's biological effects and demonstrate that, in terms of proteins, AdEV has a very specific signature. Finally, we list and suggest potential therapeutic strategies to modulate AdEV release and composition in order to reduce their deleterious effects during the development of metabolic complications associated with obesity.