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

Abstract

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 knock out of caveolin 1 (cav1) protein. While 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 between adipocytes, stromal vascular cells and potentially distal organs.

Adipocyte‐derived extracellular vesicles modulate appetite and weight through mTOR signalling in the hypothalamus

“…22,[24][25][26][27] Consistent with their results, we adopted the same method and found that 3T3-L1 adipocytes can secrete exosome-enriched EVs. 22,[24][25][26][27] Consistent with their results, we adopted the same method and found that 3T3-L1 adipocytes can secrete exosome-enriched EVs.…”

“…[22][23][24][25][26][27] A variety of EV populations are produced and released by cells, including apoptotic bodies, large microvesicles (200 nm-1 µm) and nanometric exosomes (30-200 nm), which carry proteins and nucleic acids capable of modulating the activity of target cells. [22][23][24][25][26][27] A variety of EV populations are produced and released by cells, including apoptotic bodies, large microvesicles (200 nm-1 µm) and nanometric exosomes (30-200 nm), which carry proteins and nucleic acids capable of modulating the activity of target cells.…”

Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells

“…In accord, elegant studies demonstrated the importance of EV in the dialog between adipocytes and endothelial cells (Crewe et al, 2018), as well as AT macrophages (Flaherty et al, 2019). Here, we show that a metabolic cooperation exists between adipocytes and tumor cells and is amplified in obesity, suggesting that obese cancer patients would likely benefit from FAO inhibitors and/or molecules that inhibit EV uptake.…”

Tumoral microvesicle–activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma

“…As an emerging hallmark of cancer, metabolic interaction is an important aspect of tumor‐stroma interaction (2). EVs trafficking between different kinds of cells was associated with metabolism (34). In ourprevious study, we performed a Kyoto Encyclopedia of Genes and Genomes pathway analysis of overlapping proteins in TMVs and found that proteins involved in metabolic pathways were the most abundant (11).…”