The Crewe lab uses transgenic mouse lines, cell culture and biochemistry to understand extracellular vesicle (EV)-mediated signaling during homeostatic and pathologic metabolic regulation. Crosstalk between adipocytes and cells within the adipose tissue (AT) microenvironment directs healthy tissue expansion in response to overnutrition. In contrast, the inability to coordinate these inter-cellular signals during nutrient stress results in AT hypoxia, inflammation, and fibrosis, all of which contribute to systemic metabolic disturbances in obesity and type 2 diabetes. Our work has uncovered the existence of an expansive EV-mediated signaling network within the AT proper, and from the adipose tissue to other organs. This mostly adipocyte-derived EV population consists of exosome-like vesicles that carry proteins, RNAs and lipid species that can modulate a variety of signaling pathways in recipient cells. The focus of the lab is to determine how the various cargo of adipocyte EVs, signal between cells within the adipose tissue and between the adipose tissue and distal organs to modulate metabolism in obesity.