Extracellular vesicles in metabolic disease

Abstract

Extracellular vesicles (EVs) are submicron-sized lipid envelopes that are produced and released from a parent cell and can be taken up by a recipient cell. EVs are capable of mediating cellular signalling by carrying nucleic acids, proteins, lipids and cellular metabolites between cells and organs. Metabolic dysfunction is associated with changes in plasma concentrations of EVs as well as alterations in their EV cargo. Since EVs can act as messengers between parent and recipient cells, they could be involved in cell-to-cell and organ-to-organ communication in metabolic diseases. Recent literature has shown that EVs are produced by cells within metabolic tissues, such as adipose tissue, pancreas, muscle and liver. These vesicles have therefore been proposed as a novel intercellular communication mode in systemic metabolic regulation. In this review, we will describe and discuss the current literature that investigates the role of adipose-derived EVs in the regulation of obesity-associated metabolic disease. We will particularly focus on the EV-dependent communication between adipocytes, the vasculature and immune cells in type 2 diabetes.

Keywords: Adipocytes; Diabetes; Diagnostic; Endothelial cells; Exosomes; Extracellular vesicle; Immune cells; Macrophages; Metabolic dysfunction; Platelets; Review; Therapeutic.

Fig. 1

The EV landscape at a glance from biogenesis to isolation and characterisation. (a) A schematic representation of the cellular origins of EV sub-populations, their respective classifications based on EV size, and associated markers. Apoptotic bodies are generated by apoptotic blebbing and microvesicles by budding of the plasma membrane. Exosomes are generated from late endosomal MVBs, which fuse with the plasma membrane and release small exosomes. ALIX, ALG-2-interacting protein X; HSP70, heat shock protein 70; TSG101, tumour susceptibility gene 101. (b) The stages of exosome biogenesis. Late endosomes mature into MVBs, which are targeted for degradation or fuse with the plasma membrane to release exosomes. ER, endoplasmic reticulum. (c) The most commonly used techniques for EV isolation from biological fluids: ultracentrifugation, immunoaffinity capture and size-exclusion chromatography. This figure is available as a downloadable slide