ESPEYB16 11 Obesity and Weight Regulation Metabolic Signaling (2 abstracts)
11.8. An endothelial-to-adipocyte extracellular vesicle axis governed by metabolic state
Crewe C , Joffin N , Rutkowski JM , Kim M , Zhang F , Towler DA , Gordillo R & Scherer PE
Touchstone Diabetes Center, Department of Internal Medicine, the University of Texas Southwestern Medical Center, Dallas, TX, USA, philipp.scherer@utsouthwestern.edu
To read the full abstract: Cell. 2018; 175(3): 695–708
This paper demonstrates for the first time the existence of extracellular vesicle (EV)-mediated signaling between cell types within the adipose tissue. The results of various experiments show a network of EV-mediated exchange of cellular material in adipose tissue. This newly discovered EV trafficking in adipose tissue is regulated by the metabolic state of the body.
The authors recognized the phenomenon of EV trafficking by chance when they generated an adipocyte-specific knockout of caveolin 1 (cav1). Caveolin-1 is a protein that regulate many cell functions e.g. membrane transport, endocytosis, regulation of calcium metabolism, lipid metabolism and signal transduction in cell proliferation and programmed cell death. Mutations in the CAV1 gene cause a rare form of lipodystrophy. Although they effectively ablated CAV1 in adipocytes, caveolin 1 protein remained abundant in the same adipocytes. By generating new additional mouse models, they showed in vivo that caveolin 1 protein is transferred in EVs from neighboring endothelial cells to adipocytes. In addition, they showed that adipose tissue-derived EVs contain proteins and lipids which can modulate cellular signaling pathways. Finally, they showed that this transfer is physiologically regulated by fasting and refeeding, and is dependent on fat mass. This suggests that EVs participate in the tissue response to changes in systemic nutrient state. These findings reveal a new mechanism which can be added to the complex signaling mechanisms between adipocytes, stromal vascular cells, and, potentially, distant organs.
Volume 16
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ESPE Yearbook of Paediatric Endocrinology
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