An Overview of Inter-Tissue and Inter-Kingdom Communication Mediated by Extracellular Vesicles in the Regulation of Mammalian Metabolism

Figures

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  Figure 1. EV biogenesis in plants, mammals, and bacteria. Aside from apoptotic bodies generated upon programmed cell death, plant and mammalian cells release two main types of EVs: MVs resulting from plasma membrane evaginations and exosomes formed when the membrane of early endosomes invaginates in the intracellular space, engulfing a portion of the cytoplasm and giving rise to a multivesicular body (MVB) that may then fuse with lysosomes to recycle cellular components or with the plasma membrane, hence releasing the exosomes to the extracellular space. Alternatively, Gram-negative bacteria have two routes for bEV formation: blebbing of the outer membrane caused by cell cover disturbances leads to the production of OMVs that do not contain cytoplasmic components, whereas explosive cell lysis initiated by phage-derived endolysin that degrades the peptidoglycan cell wall results in cells bursting and releasing membrane fragments that self-assemble into OIMVs, which contain cytoplasmic components. In Gram-positive bacteria, endolysin triggers bubbling cell death, which is induced by DNA-damaging stress and results in CMVs that contain membrane and cytoplasmic components.

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  Figure 2. EVs and their cargo participate in inter-organ crosstalk to regulate metabolic homeostasis. EVs released by many cell types can be captured by acceptor cells in an autocrine and paracrine manner, initiating biological responses. In addition, EVs can go into the circulation and reach other organs, driving inter-organ crosstalk. M1: M1 macrophages; M2: M2 macrophages. See text for details.

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  Figure 3. Impact of dietary patterns on gut microbiota composition and bEV profile and its effects on metabolic diseases. Unhealthy dietary patterns contribute to obesity and T2D by promoting gut microbiota dysbiosis. The increase in detrimental bEVs may then affect gut barrier permeability and intestinal inflammation. After gaining access to the systemic circulation, bEVs may disturb peripheral organ function, thus impairing metabolic homeostasis and promoting inflammation, thereby increasing the severity of metabolic disorders. Conversely, an increase of beneficial bEVs through a plant-based diet or probiotic supplements could be a strategy to treat metabolic disorders by counteracting dysbiosis, gut permeability, inflammation, metabolic homeostasis disturbances, and nervous system imbalance. See text for details.

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  Figure 4. EVs found in edible vegetables or milk, or released by the gut microbiota and the different organs, participate in a multi-directional, inter-kingdom crosstalk that is required to coordinate metabolic processes and maintain homeostasis in the host. See text for details.