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Cell. 2018 Oct 18;175(3):695-708.e13. doi: 10.1016/j.cell.2018.09.005. Epub 2018 Oct 4.

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

Author information

1
Touchstone Diabetes Center, Department of Internal Medicine, the University of Texas Southwestern Medical Center, Dallas, TX, USA.
2
Touchstone Diabetes Center, Department of Internal Medicine, the University of Texas Southwestern Medical Center, Dallas, TX, USA; Cardiovascular and Metabolic Disease Center (CMDC), Inje University, Busan, South Korea.
3
Touchstone Diabetes Center, Department of Internal Medicine, the University of Texas Southwestern Medical Center, Dallas, TX, USA; Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
4
Department of Internal Medicine, Endocrine Division, the University of Texas Southwestern Medical Center, Dallas, TX, USA.
5
Touchstone Diabetes Center, Department of Internal Medicine, the University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: philipp.scherer@utsouthwestern.edu.

Abstract

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.

KEYWORDS:

adipose tissue; caveolin 1; endothelial cells; exosome; extracellular vesicle; fasting; glucagon; metabolism; obesity

Comment in

PMID:
30293865
PMCID:
PMC6195477
DOI:
10.1016/j.cell.2018.09.005
[Indexed for MEDLINE]
Free PMC Article

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