An Endothelial-to-Adipocyte Extracellular Vesicle Axis Governed by Metabolic State.

Summary We have uncovered the existence of extracellular vesicle (EV)-mediated signaling between cell types within the adipose tissue (AT) proper. This phenomenon became evident in our attempts at generating an adipocyte-specific knockout of caveolin 1 (cav1) protein. Although we effectively ablated the CAV1 gene in adipocytes, cav1 protein remained abundant. With the use of newly generated mouse models, we show that neighboring endothelial cells (ECs) transfer cav1-containing EVs to adipocytes in vivo , which reciprocate by releasing EVs to ECs. AT-derived EVs contain proteins and lipids capable of modulating cellular signaling pathways. Furthermore, this mechanism facilitates transfer of plasma constituents from ECs to the adipocyte. The transfer event is physiologically regulated by fasting/refeeding and obesity, suggesting EVs participate in the tissue response to changes in the systemic nutrient state. This work offers new insights into the complex signaling mechanisms that exist among adipocytes, stromal vascular cells, and, potentially, distal organs. Graphical Abstract Highlights • A network of EV-mediated exchange of cellular material exists in adipose tissue • This exchange can replace protein levels in adipocytes despite gene disruption • EV trafficking in adipose tissue is regulated by the systemic metabolic state • Endothelial cells pack extracellular molecules in EVs for release to adipose tissue Extracellular vesicles exchange protein and lipid signals between endothelial cells and adipocytes conveying information about nutrient state changes from the blood in adipose tissues. [ABSTRACT FROM AUTHOR]