Roles of extracellular vesicles derived from healthy and obese adipose tissue in inter-organ crosstalk and potential clinical implication

Figures

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  Figure 1. Schematic illustration of EV biogenesis and potential clinical applications. EVs are secreted into extracellular space and can be classified into three subgroups: exosomes (50-150 nm), microvesicles (150-1000 nm), and apoptotic bodies (1-5 µm). Exosomes are formed through the endocytic pathway and secreted by the fusion of MVBs with the plasma membrane. Microvesicles are formed directly from the plasma membrane. And apoptotic bodies are formed by cellular budding and the creation of apoptotic protrusions. EVs can be used as disease biomarkers and therapies. EVs derived from blood or body fluid carry specific cargoes that reflecting the state of parent cells, making them potential biomarkers for multiple diseases. Also, EVs derived from MSC, DC or platelet lysate also serve as promising therapeutic agents in various diseases. MVB, multivesicular body; ILV, intraluminal vesicles; ELISA, enzyme-linked immunosorbent assay; MSC, mesenchymal stem cells; DC, dendritic cells. This figure was created by using BioRender (https://biorender.com/).

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  Figure 2. A graphic workflow for the isolation procedures of AT-EVs. The adipose tissues separated from human or other experimental animals were cut into small pieces on ice and incubated in medium for 24 h at 37 °C. Filtration and low force centrifugation (300 ×g for 15 min and 3,000 ×g for 15 min) were used to remove tissue pieces, cells and debris. After centrifugation at 10,000 ×g for 40 min, the large EVs were collected. The subsequent supernatant, after filtration through a 0.22 µm filter, the small EVs were isolated by multiple methods, including ultracentrifugation, precipitation, membrane affinity, polymer-based precipitation solution, and tangential flow filtration. This figure was created by using BioRender (https://biorender.com/).

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  Figure 3. A graphic summary of the mediation of inter-organ crosstalk by BAT-EVs and WAT-EVs. Under cold stress conditions, BAT-EVs regulate systemic glucose metabolism by promoting hepatic gluconeogenesis through the effects of miR-378a. BAT-EVs also reverse obesity through two mechanisms. Firstly, their abundant mitochondrial components promote the oxygen consumption of recipient cells. Secondly, the NPM3 protein in BAT-EVs enhances the expression of browning related genes, thus inducing WAT browning. Additionally, BAT-EVs participate in the maintenance of reproductive system function by enhancing the mitochondrial function, thereby delaying ovarian aging. WAT-EVs improve skin wound healing through the effects of miR-92a-3p, which enhances the proliferation, migration, and ECM deposition of keratinocytes and fibroblasts. WAT-EVs also contribute to soft tissue healing in specific diseases, such as BRONJ. BAT, brown adipose tissue; WAT, white adipose tissue; NPM3, nucleophosmin3; ECM, extracellular matrix; BRONJ, bisphosphonate-related osteonecrosis of the jaw. This figure was created by using BioRender (https://biorender.com/).

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  Figure 4. The roles of obese AT-EVs in cancer, metabolic disorders and other diseases. The obese adipose tissue exhibits elevated ROS, with adipokines alteration and abundant immune cells infiltration. The obese AT-EVs promote the progression of several types of cancers, including breast cancer and prostate cancer. Also, obese AT-EVs enhance the formation of micronucleus and promote the irradiated cancer cell survival. Additionally, obese AT-EVs can be transferred to distal organs to induce cognitive decline, insulin resistance, colitis, disruption of immune homeostasis and increasing risk of cardiac dysfunction in infants. ROS, reactive oxygen species; AT-EVs, adipose tissue-derived extracellular vesicles. This figure was created by using BioRender (https://biorender.com/).

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  Figure 5. The comparison of ADSC-EVs and lipoaspirate-EVs. The ADSC-EVs were obtained from cell culture and lipoaspirate-EVs were obtained directly from acellular fraction. They vary in the yield, abundance of protein, miRNAs, fatty acids, and glycerolipids. ADSC-EVs and lipoaspirate-EVs both have the function of anti-inflammatory, anti-oxidant, and anti-apoptotic. Additionally, lipoaspirate-EVs have the therapeutic potential in promoting fat graft survival, wound healing, and lung injury recovery. ADSCs, adipose-derived stem cells; TFF, tangential flow filtration. This figure was created by using BioRender (https://biorender.com/).