Open Access

Adipose tissue‑derived extracellular vesicles:
Systemic messengers in health and disease (Review)

  • Authors:
    • Xiaobo Yang
    • Jiayue Hao
    • Jie Luo
    • Xinliang Lu
    • Xianghui Kong
  • View Affiliations

  • Published online on: August 23, 2023
  • Article Number: 189
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Adipose tissue (AT) is a complicated metabolic organ consisting of a heterogeneous population of cells that exert wide‑ranging effects on the regulation of systemic metabolism and in maintaining metabolic homeostasis. Various obesity‑related complications are associated with the development of dysfunctional AT. As an essential transmitter of intercellular information, extracellular vesicles (EVs) have recently been recognized as crucial in regulating multiple physiological functions. AT‑derived extracellular vesicles (ADEVs) have been shown to facilitate cellular communication both inside and between ATs and other peripheral organs. Here, the role of EVs released from ATs in the homeostasis of metabolic and cardiovascular diseases, cancer, and neurological disorders by delivering lipids, proteins, and nucleic acids between different cells is summarized. Furthermore, the differences in the sources of ADEVs, such as adipocytes, AT macrophages, AT‑derived stem cells, and AT‑derived mesenchymal stem cells, are also discussed. This review may provide valuable information for the potential application of ADEVs in metabolic syndrome, cardiovascular diseases, cancer, and neurological disorders.


Obesity has rapidly become a widespread public health concern, the incidence of which has gradually increased over numerous decades. By 2025, the World Health Organization predicts that one in five adults will be obese globally (1). Obesity is a highly heterogeneous and complicated disorder caused by unbalanced energy metabolism. In addition, obesity is also closely associated with the pathogenesis of various metabolic diseases, such as type 2 diabetes mellitus (T2D), dyslipidemia, and cardiovascular diseases (CVDs), including hypertension and stroke, neurological disorders, musculoskeletal disease, and certain types of cancer (for example, breast, liver, ovarian, kidney, prostate and colon cancer) (2). Furthermore, several studies have found that obese patients with associated comorbidities are more susceptible to SARS-CoV-2, exhibiting a higher risk of death (35).

Adipose tissues (ATs) are complex tissues that primarily exhibit a regulatory function. In mammals, ATs are primarily classified into white AT (WATs) and brown AT (BATs). In addition to metabolizing fat into energy, ATs also serve as a critical endocrine organ that can regulate energy metabolism, immunological responses, and cardiovascular balance by secreting a variety of adipokines, peptide hormones, and cytokines (6). Over the years, ~100 adipokines have been identified (7). Adipokines have a wide range of physiological effects on tissues and organs in different systems, such as the nervous system, immune system, and vascular system (8). For example, ATs secrete adiponectin that can promote insulin sensitivity and the antiatherosclerotic properties of cells by binding to adiponectin receptor (AdipoR) 1 and AdipoR2 (911). An inverse association exists between circulating adiponectin and obesity-related cancer incidence (11). Furthermore, adiponectin acts as an essential metabolic reprogramming factor by promoting the interaction between adaptor protein, phosphotyrosine interacting with PH domain, and leucine zipper 1 (APPL1) and AMP-activated protein kinase (AMPK), promoting glucose uptake through glucose transporter 4 (GLUT4) (12). The release of leptin by adipocytes was correlated with alterations in cell metabolism, such as the switch from mitochondrial β-oxidation to aerobic glycolysis (13). Chronic inflammation is another well-established characteristic of obesity (14). In obesity, there is an increase in oxidative stress and inflammation, leading to an increased release of proinflammatory adipokines, which can contribute to insulin resistance in the liver, muscles, and ATs, resulting in metabolic abnormalities (15). Studies have shown a positive correlation between obesity, insulin levels, insulin resistance, and increased tumor necrosis factor (TNF)-α production in human adipocytes (16).

In addition to the classical polypeptide adipokines and cytokines, ATs can also produce and secrete extracellular vesicles (EVs) (17). The composition of all EVs is similar to that of the parent cells, packed with bioactive molecules such as lipids, proteins, and DNA delivered to cells within ATs or in distant organs, mediating intercellular and interorgan communication (14). In this context, AT-derived extracellular vesicles (ADEVs) have been identified as crucial players in the cellular communication of immune and metabolic responses, regulating cellular processes in local and distant tissues (18,19). This review will focus on the compositions and functions of ADEVs from different cellular sources in ATs and their contribution to AT homeostasis and the development of metabolic complications, such as metabolic diseases, CVDs, several types of cancer, and neurological disorders.

Introduction to EVs

Initially, EVs were viewed as a quality control system to eliminate harmful or unnecessary molecules from the cell (20). EVs are now identified as a group of submicron-sized membrane-bound organelles secreted by almost all cells, carrying several biological cargoes, such as lipids, fatty acids (FAs), and nucleic acids, capable of targeting and transferring their contents to various receptor cells within the tissue or distal tissues (Fig. 1). EVs primarily consist of exosomes, microvesicles (MVs) and apoptotic bodies (21). Apoptotic bodies are known to be produced during apoptotic cell death and have a diameter >5 µm (22). MVs are small vesicles (100–1,000 nm size range) formed by plasma membrane fusion and budding. Although the exact process by which MVs are formed is not fully understood, cytoskeletal elements such as actin and microtubules, coat proteins, and fusion machinery, such as SNAREs, are hypothesized to be necessary. Specifically, coat proteins such as clathrin and cytoplasmic coat protein complex, are drawn to the membrane to reshape the flat membranes into rounded buds, cargo, and vesicle-SNAREs (v-SNAREs, primarily including VAMP) are integrated into the budding vesicle by attaching to coat subunits, for example, adaptor protein (AP) complexes (23). In addition, the molecular composition of MVs primarily consists of cytoplasmic and plasma membrane-associated proteins since MVs are formed by the outward budding of the membrane, and they may vary greatly depending on the cell type (24). In addition, MVs were first described as subcellular material originating from platelets and were demonstrated to play a role in blood coagulation (25,26). More recently, they have been reported to transfer cargo to target cells, thus playing an essential role in cell communication (27). Exosomes are vesicles 30–150 nm in diameter secreted by the endosome pathway. During the biogenesis of exosomes, endocytosis-mediated invagination of the plasma membrane (PM) forms early endosomes. Endosomal membranes bud inward into the lumen to create intraluminal vesicles (ILVs). These late endosomes contain ILVs called multivesicular bodies (MVBs). MVBs can fuse with lysosomes to be degraded or fuse with the PM to release ILVs as exosomes into the extracellular environment (28,29).

The nature and abundance of EV cargoes are specific to the cell type. They are frequently affected by the state of donor cells and the molecular processes that result in their biogenesis (30,31). EVs are loaded with various biomolecular components, such as nucleic acids and proteins, contributing to their functional diversity, heterogeneity, and complexity. Proteins commonly found in EVs are those associated with biogenetic mechanisms, including those related to endosomal pathways. Several membrane proteins and transcription factors can also be found in EVs (32,33). EVs are rich in sphingomyelin, cholesterol, desaturated lipids, phosphatidylserine, and ceramide (34). In addition, a range of genetic material is found in EVs, such as DNA, mRNAs, microRNAs (miRNAs), and several noncoding RNAs (ncRNAs). As soon as EVs bind to target cells, they may remain in the PM or be ingested through endocytosis, direct membrane fusion, and ligand binding mechanisms (3537).

Proteins of the tetraspanin family, such as CD81 and CD9, are enriched in EVs and considered unique markers of EVs, including exosomes and MVs (38). However, researchers have demonstrated that CD81, CD63, and CD9 are exosome markers in a recent study on the difference between exosomes and MVs (39). At the same time, they emphasized that Annexin A1 is present in MVs, not exosomes. Furthermore, MVs also contain several biological molecules, such as integrins, selectins, and CD40 ligands, which may facilitate the formation of MVs (40,41). Therefore, more research is required to distinguish them from each other. In the present review, ‘EVs’ is used to refer to exosomes and MVs only.

AT and ADEVs


ATs are complex metabolic organs with profound effects on regulating systemic metabolism, energy storage, and homeostasis. The primary characteristic of BATs is the presence of multilocular lipid droplets and several mitochondria expressing high levels of uncoupling protein 1 (UCP1), responsible for nonshivering thermogenesis, leading to increased energy expenditure (42). WATs primarily consist of white adipocytes, which carry large lipid droplets and fewer mitochondria, making them the primary site for storing and releasing energy (42). In addition, studies have shown that WATs can undergo a process called ‘browning’, during which part of the white adipose tissue can be transformed into beige adipose tissue (BeATs), morphologically distinct from WATs and BATs (43,44). Browning occurs under certain circumstances, such as in the cold and as a result of exercise. Moreover, medicines, such as β-adrenergic receptor and peroxisome proliferator-activated receptor (PPAR)γ agonists, can also trigger browning by promoting the decomposition of triglyceride and glucose in ATs or by inducing the expression of thermogenesis-related genes, respectively, which ultimately encourages lipolysis and thermogenesis (4547). Characteristically, beige adipocytes contain several small lipid droplets, are typically larger than brown adipocytes, have more mitochondria than white adipocytes, and express UCP1 (48). Additionally, these types of ATs differ in critical ways that include aspects of their gene expression profile and secretome. WAT, known as the active endocrine organ, can release cytokines and adipokines such as leptin and adiponectin (6). In contrast, BAT/BeAT have fewer secretory functions than WAT. In addition to UCP1, Cell death-inducing DFFA like effector a, Cytochrome c oxidase subunit 7A1, and ELOVL fatty acid elongase 3 are specifically expressed in BAT, while BeAT expresses T-box transcription factor 1, Solute carrier family 27 member 1, Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1, CD40 and CD137 (49,50). Since the UCP1 expression of beige adipocytes is considerably lower than those of classical brown adipocytes, BeATs were once considered unimportant in whole-body energy expenditure (51). However, in adults with a minimal classic BAT reserve, BeATs are the primary energy source for nonshivering thermogenesis (52). Additionally, BeATs regulate whole-body energy metabolism and glucose homeostasis through an UCP1 independent mechanism (51). According to the report, activation of BeATs with β-adrenergic agonist CL316243 enhanced the selective uptake of fatty acids from triglyceride-rich lipoproteins by ATs, and reduced plasma TG and cholesterol levels, thereby alleviating hypercholesterolemia and atherosclerosis (53). Another study showed that prolonged maintenance of thermogenically active BeATs enhanced whole-body energy expenditure and protected mice from diet-induced obesity and insulin resistance (54). As the most abundant form of AT, WAT is distributed throughout the body and are active endocrine organs. They release free fatty acids and adipokines, such as leptin, adiponectin, TNF-α, and IL-6, which act on distal tissues, including the brain, liver, and muscle tissue, to regulate food intake, energy homeostasis, and insulin sensitivity (55). The ATs found in the hypodermis layer are called subcutaneous ATs (SCATs), and form a connective tissue in the dermis between the aponeurosis and the muscle fascia, insulating and storing energy. SCATs are primarily distributed in the abdominal and gluteofemoral regions of the human body, storing >80% of total body fat (56). Dermal WATs (DATs), located directly below the reticular dermis (primarily above the SCATs), have been reported to be involved in insulation, hair regeneration, wound healing, and the prevention of skin infections (57,58). In addition, WATs that accumulate around internal organs are visceral ATs (VATs), which are primarily found in the intrathoracic region and abdominal cavity, such as epicardial and pericardial fat and perigonadal, mesenteric, perirenal, and retroperitoneal fat, protecting the internal organs of rodents and humans and storing 5–20% of total body fat (59,60).

Cellular composition of ATs

ATs are connective tissues primarily made up of lipid-rich cells known as adipocytes. Adipocytes, the parenchymal cells of ATs, are critical regulators of energy metabolism and endocrine modulators engaged in numerous physiological or pathological processes, such as appetite regulation and immunological response (61,62). In addition to adipocytes, there are several nonadipocyte compartments termed the stromal vascular fraction (SVF), composed of AT-derived stem cells (ADSCs), preadipocytes, endothelial cells, and a broad spectrum of adaptive and innate immune cells (6366). Preadipocytes can differentiate into mature adipocytes to maintain adipogenesis and homeostasis in adipose tissue (67). The ADSCs in ATs are mesenchymal stem cells (MSCs) of mesodermal origin, serving as progenitors responsible for adipocyte regeneration and replenishment. ADSCs also have potent self-renewal capacity and a high capacity for classical adipogenic, osteogenic, and chondrogenic differentiation. In addition to mesenchymal cells, ADSCs can differentiate into nonmesenchymal cell lineages, such as endothelial cells, myocytes, and neuronal lineages (68). Endothelial cells and pericytes provide vasculature to ATs by forming capillaries (6971). The immune cell types and functions of ATs have been widely discussed, primarily in the context of obesity. Various immune cells form a dynamic immunological microenvironment with variable metabolic status, including macrophages, eosinophils, dendritic cells (DCs), invariant natural killer cells (iNKT cells), T cells, and B cells (7274). For example, under conditions of obesity or chronic metabolic stress, increased infiltration and activation of proinflammatory immune cells can accelerate WAT inflammation, thus influencing the effect of insulin and other metabolic hormones on parenchymal cells, thus further damaging the glucose and lipid metabolism process of metabolic organs (7577).

Working model and the source of ADEVs

Although EVs are physiologically released from cells, pathophysiological stimuli can regulate their biogenesis and release. Furthermore, certain proteins and mRNAs can be selectively packaged into EVs during physiological changes or pathological injuries. Similar to normal EVs, ADEVs exert their biological functions by transporting bioactive cargos such as miRNAs, ncRNAs, proteins, and lipids to receptor cells. Studies have shown that ADEVs can not only modulate the immune responses of local ATs through cellular communication but can also regulate systemic insulin sensitivity and glycolipid metabolic processes through their remote effects on other metabolic organs (for example, the brain and liver) (7880) (Fig. 2). Research has shown that ADEVs directly modulate glucose tolerance and insulin sensitivity in adipocytes, myocytes, and hepatocytes through modulation of PPARγ and perhaps fibroblast growth factor 21 (81,82). In the brain, ADEVs derived from adipocytes have been shown to carry the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and to activate the mTOR signaling pathway through miR-181b and miR-144 in hypothalamic anorexigenic pro-opiomelanocortin (POMC) neurons, thereby leading to increased appetite and body weight (83). In addition, analysis of the protein profiles of EVs derived from adipocytes confirmed that EVs from obese mice are enriched in proteins and enzymes involved in the metabolism and transport of lipids, such as caveolin 1, lipoprotein lipase, and aquaporin 7, which may be associated with ectopic lipid accumulation and lead to mitochondrial energy metabolism disturbance, and systemic insulin resistance (84,85). In particular, quantitative proteomic analysis of EVs released by 3T3-L1 adipocytes showed that enzymes related to de novo lipogenesis, including glucose-6-phosphate dehydrogenase and fatty acid synthase, were selectively enriched in EVs from adipocytes, promoting lipid accumulation in recipient adipocytes and preadipocytes (85).

Most of the current body of knowledge on ADEVs comes from studies using 3T3-L1 cells. These studies found that ADEVs are highly adipocyte-specific and can be identified from complicated heterogeneous origins, such as plasma (86,87). Currently, multiple types of cells in ATs, such as adipocytes, ADSCs, and macrophages, have been shown to release EVs, mediating intercellular and interorgan crosstalk and regulating ATs and systemic homeostasis (88,89). EVs derived from adipocytes have been reported to carry proteins or enzymes involved in fatty acid oxidation (FAO), which can induce metabolic reprogramming and stimulate the migration and invasion of melanoma cells when EVs are taken up by tumor cells, thus amplifying the deleterious dialog between cancer cells and adipocytes (78,90). Furthermore, EVs derived from AT macrophages (ATMs) can modulate mouse glucose tolerance and insulin sensitivity (81,91). ADSCs have a high capacity for differentiation into multiple cell types and play an essential role in immune regulation (9294). EVs released from ADSCs may at least be partially responsible for some of these functions. ADSC-derived EVs (ADSC-EVs) obtained from patients with or without cancer show equivalent miRNA content, which suggests that ADSC-EVs have the same therapeutic paracrine effects regardless of the health status of the donor (95). Previous studies have found that delivering ADSC-EVs from lean mice to obese mice showed desirable effects on alleviating obesity and IR (96). Additionally, ADSC-EVs obtained from human WATs and BATs can induce ADSCs to differentiate into WATs and BATs, respectively, attenuating diet-induced obesity, glucose tolerance, and liver steatosis (97). These findings suggest that ADEVs can be used as cell-free therapeutics for AT regeneration and remodeling.

ADEVs in disease

ADEVs regulate metabolic disorders

AT dysfunction is accompanied by chronic low-grade inflammation, in which excessive adipokine synthesis and secretion are closely related to cardiovascular, chronic liver, and kidney diseases as well as other systemic metabolic disorders (98,99). The inflammation of WATs caused by obesity is characterized by the accumulation of macrophages, including monocyte-derived macrophages (moMacs). Moreover, obese WAT monocytes can differentiate locally into moMacs and contribute to ATM pools (100). During the development of obesity, macrophages transition from an anti-inflammatory phenotype to a proinflammatory phenotype, producing proinflammatory factors and exacerbating adipose inflammation (101). Initially, ADEVs were shown to be taken up by peripheral monocytes, which then differentiated into macrophages that increased TNF-α and IL-6 secretion, leading to insulin resistance and glucose intolerance through the Toll-like receptor 4/TIR domain-containing adaptor molecule 1 pathway (102). Notably, a recent study revealed a mechanism by which adipocytes regulate ATM polarization through EVs. ADEVs derived from mature adipocytes containing miR-34a inhibited macrophage M2 polarization by downregulating Krüppel-like factor 4, a crucial transcription factor for maintaining an adipose M2 macrophage phenotype, thereby leading to adipose inflammation (103). Several immunomodulatory proteins, such as macrophage migration inhibitory factor, retinol-binding protein 4, and soluble adiponectin, have been identified in EVs from cultured human adipocytes and human AT explants, which may induce monocytes to differentiate into M1-phenotype macrophages, exacerbating adipose inflammation and insulin resistance (86).

Insulin resistance (IR) is a disordered biological response in which the body cannot respond to high insulin levels or absorb and utilize glucose normally, causing the body to produce more insulin in response. It is the critical cause of several metabolic syndromes, such as T2D and obesity (104). As mentioned above, ADEVs from the VATs of obese mice were enriched in fatty acid binding protein 4 (FABP4) and induced the differentiation of macrophages to the M1 phenotype. In addition, those ADEVs were shown to be taken up by monocytes and to induce IR (102). Ying et al (91) found that injecting ATM-derived EVs from obese mice into lean mice inhibited the expression of PPARγ, which can promote whole-body lipid metabolism and insulin sensitivity, and GLUT4 (a PPARγ target gene), thereby reducing adipocyte sensitivity to insulin. Specifically, EVs containing miR-155 derived from ATMs target PPARγ in adipocytes, the liver, and the muscle, regulating insulin activity (91). In addition, adipocytes secrete EVs containing miR-27a, a negative regulator of PPARγ, leading to PPARγ-dependent obesity-induced IR by directly binding to the 3′UTR of PPARγ (105). Subsequently, ATM-derived EVs from obese mice were confirmed to possess miR-29a and to cause IR by binding to the 3′UTR of PPARδ (a potent modulator of insulin sensitivity) in adipocytes, myocytes, and hepatocytes (81). Another study showed that miR-222 from gonadal WAT-derived EVs promoted IR in the liver and skeletal muscle by suppressing IRS-1 expression via binding to the 3′UTR of IRS-1 (106). In contrast, ADSC-EVs facilitated metabolic homeostasis and improved insulin sensitivity in obese mice by alternatively activating M2 macrophage polarization and reducing inflammation by activating arginase-1 through STAT3 carried by EVs (96). In addition, miR-27a was enriched in adipocyte-derived EVs isolated from the VATs of obese individuals, and those EVs were shown to contribute to IR in the liver and skeletal muscle by inhibiting insulin-induced Akt phosphorylation and PPARα expression (107).

Given that obesity is a risk factor for the development of T2D, research has focused on the relationship between ATs and diabetes/diabetic complications. As no definitive marker of ADEVs has yet been identified, it is challenging to elucidate the detailed role of ADEVs in obesity and metabolic syndromes such as T2D. The production and specific cargo of ADEVs are altered under metabolic stresses (108). Perilipin A levels were higher in circulating adipocyte-derived EVs from obese mice and humans with metabolic diseases (109). AT-derived miRNAs are the main circulating EV miRNAs (18). A study showed that miR-20b-5p was abundant in serum EVs of T2D patients, and miR-20b-5p modulated insulin action in skeletal muscle by downregulating Akt interacting protein (AKTIP) and STAT3 expression (110). In addition, certain ADEVs exert beneficial effects on T2D. A previous study assessed the relationship between metabolic syndrome and adipose tissue-derived EV markers, and revealed that individuals with CD14-positive EVs had a 16% lower risk of developing T2D after 6.5 years of follow-up (111). EVs derived from activated beige adipocytes contain diabetes-preventing factors. When administered to primary white adipocytes, these EVs improved insulin sensitivity and insulin-stimulated glucose uptake (112). Together, based on these studies, adipose-derived EVs are viewed as a novel cellular communication tool within ATs and perhaps between ATs and distant organs to regulate T2D.


Dysfunctional ATs in obese individuals can lead to an increased risk of CVD, which remains one of the principal causes of death worldwide, despite advances in risk factor management (113115). To date, efficient treatments for CVD are lacking. Recently, ADEVs have emerged as critical actors in the crosstalk between obesity and CVD progression.

Aside from polarization, macrophage foaming also plays a vital role in the progression of atherosclerotic lesions. ADEVs from VATs in obese mice facilitate macrophage foam cell generation by downregulating ATP binding cassette subfamily A member 1 (ABCA1) and ATP binding cassette subfamily G member 1 (ABCG1)-mediated cholesterol efflux and exacerbated atherosclerosis (116). ADEVs from adipocytes and their miRNA contents were confirmed to reduce macrophage cholesterol efflux by targeting ABCA1, thus promoting the development of atherosclerosis (117). In contrast, another study identified the beneficial effects of EVs derived from ADSCs in cardiac recovery, highlighting their potential in regenerative therapy (118). In addition, studies on 3T3-L1 models showed that adipocyte-derived EVs containing miR-802-5p promoted IR in cardiomyocytes by downregulating heat shock protein 60, which has been proven to prevent inflammation, mitochondrial dysfunction, and even insulin resistance (119).

Coronary artery disease and atherosclerosis are caused by endothelial dysfunction during the early stages of the disease (120). It is not well understood how EVs are exchanged between adipocytes and endothelial cells during obesity despite extensive evidence of proinflammatory crosstalk between ATMs and ADEVs. It was found that hypertrophic and dysfunctional adipocytes release EVs that impair vascular endothelial cell function, potentially contributing to obesity-related atherosclerosis (121). In addition, research has demonstrated that hypoxia and inflammation promote synergistic EV production from adipocytes. These ADEVs promote the expression of endothelial vascular cell adhesion molecule 1 (VCAM-1), which increases the subsequent attachment of leukocytes to endothelial cells and exacerbates vascular disease in obesity (122).

One of the causes of heart failure is cardiac hypertrophy (CH). Research has shown that miR-200a in ADEVs derived from adipocytes can be transferred into cardiomyocytes to inhibit TSC1 and activate the mTOR pathway, leading to CH. It was also shown that inhibition of miR-200a could abrogate CH (123). In addition, Gan et al (124) demonstrated that ADEVs derived from diabetic adipocytes were delivered to cardiomyocytes where they facilitated the pathogenic interaction between the heart and defective ATs, aggravating ischemic heart damage in obese/diabetic individuals. miR-130b-3p was found to be a vital agent mediating this proapoptotic effect of diabetic adipocyte-derived EVs and identified AMPK as a novel target of miR-130b-3p, in which miR-130b-3p was shown to impair the expression of AMPK, the latter of which is a crucial regulator of metabolic disorder-induced cellular malfunction and cell death (124). However, the precise role of ADEVs is still poorly understood in the context of CVD and requires further investigation.

ADEVs as major actors in cancer

An increasing body of data from animal and human studies indicates that obesity increases the risk of developing cancer, cancer-associated mortality, and cancer recurrence following treatment (125). Previously, studies on the communication between adipocytes and tumor cells have been limited to cytokines such as endorphin, leptin, or chemokines. Then, the discovery of cancer-associated adipocytes (CAAs) revealed a vicious cycle in which tumors activate CAAs, and CAAs can further contribute to tumor progression by secreting adipokines, inflammatory cytokines, and metabolites (126,127). More recently, the role of ADEVs in tumor–adipose tissue communication has also been confirmed, and obesity modifies ADEV secretion quantitatively and qualitatively, thus amplifying their effect on tumor aggressiveness.

The first line of evidence linking ADEVs with cancer showed that ADEVs from different adipocyte models enhanced melanoma cell migration, invasion, and lung metastases in the context of obesity (90). Subsequently, Wang et al (128) showed that EVs derived from 3T3-L1 adipocytes induced lung tumor metastasis by increasing MMP9 activity of 3LL lung cancer cells, in which MMP9 has been shown to promote tumor invasion and metastasis. Another study demonstrated that ADEVs from AT-derived mesenchymal stem cells (ADMSCs) could foster the invasion, migration, and proliferation of osteosarcoma cells by increasing galactosyl transferase 2 and MMP2/9 expression (129). Gangadaran et al (130) demonstrated that ADSC-EVs contain angiogenic proteins such as IL-8, CCL2, TIMP-1, TIMP-2, and VEGF-D. Following internalization of ADSC-EVs, endothelial cells undergo differentiation, develop a tube-like formation and promote angiogenesis in vitro and in vivo. Khanh et al (131) showed that in patients with T2D, ADEVs derived from ADMSCs can promote breast cancer metastasis by targeting the JAK/STAT3 pathway. In conditions of obesity, ADEVs from AT macrophages are rich in miR-155, which is not only involved in IR but also plays an oncogenic/antiapoptotic role through caspase-3 and Bcl-2 in breast cancer cells (132).

By contributing local FAs to the process of FAO within tumor cells, a novel beneficial metabolic route is activated that increases tumor aggressiveness and proliferation, and adipocytes also aid in the evolution of tumors through metabolic collaboration (90,133,134). The proteins, including the enzymes needed for FAO, can be transferred to cancer cells or across farther distances by ADEVs released by adipocytes. Lazar et al (90) demonstrated that proteins implicated in FAO were enriched in ADEVs, which were then taken up by melanoma cells, leading to increased lung metastases and an increase in FAO in tumor cells. Clement et al (78) revealed the role of ADEVs in the crosstalk between melanoma cells and adipocytes, which triggers metabolic remodeling and ultimately facilitates the FAO process and tumor aggressiveness. In addition to FAO enzyme transfer, ADEVs also deliver FAs to tumor cells to enhance the FAO process, reinforcing the effect of ADEVs on obesity. Together, this research revealed that ADEVs are involved in guiding the growth, invasion, metabolic reprogramming, and metastasis of cancer cells by modulating the acquisition and maintenance of cancer markers.

Effects of ADEVs on neurological disorders

Neurological disorders, including neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as ischemic stroke, are often characterized by neuroinflammation. Treating neurological disorders has long been challenging as many therapeutics do not cross the blood-brain barrier (BBB). To date, EVs carrying biological molecules are recognized as an excellent tool for treating central nervous system (CNS)-related ailments since they are prospective drug delivery systems that can cross the BBB (135).

The deposition of β-amyloid peptide (Aβ) in the brain and neurofibrillary tangles (NFTs) formed by hyperphosphorylated Tau protein plays a critical role in the pathogenesis of AD (136,137). According to Katsuda et al (138), ADSC-derived EVs carried enzymatically active neprilysin (NEP), the brain's most important Aβ-degrading enzyme. Furthermore, Aβ levels were decreased when ADSC-derived EVs were transfused into N2a neuroblastoma cells in vitro. Another study demonstrated that ADSC-derived EVs inhibited inflammatory polarization of activated human microglia, which has been shown to mediate several CNS inflammatory processes, such as AD (139). In another rat model of ischemic stroke, ADSC-derived EVs containing miR-126 were shown to prevent ischemic stroke, promote neurogenesis, and vasculogenesis following ischemic stroke, and inhibit ischemic stroke-induced microglial activation and inflammatory responses (140). Jiang et al (141) showed that EVs derived from ADSCs suppress autophagy by inhibiting the expression of Beclin-1 and Atg5 via miR-30d-5p, thereby promoting microglial M2 polarization and ultimately preventing acute ischemic stroke. These characteristics make ADSC-derived EVs promising candidates for therapeutic relevance in neurodegenerative diseases.

Conclusions and future directions

In addition to the classical polypeptide adipokines and cytokines, the critical role of ADEVs in communication between ATs and other organs has been gradually deciphered. More recently, growing evidence from both epidemiologic and preclinical studies further highlights the effects of ADEVs on mediating cell-to-cell communication within ATs, and between ATs and other peripheral organs. A comprehensive understanding of the interaction patterns between ATs and other tissues and the molecular changes in AT dysfunction during obesity, such as ADEVs and their cargoes, may provide novel avenues for developing new therapeutic interventions in obesity-related metabolic diseases.

EVs have long been recognized as crucial intercellular communication tools. In addition, EV-mediated cellular communication is implicated in various diseases and biological events, including certain immune responses such as inflammation. Therefore, EVs are also considered a therapeutic target for multiple diseases (142). In addition, due to their endogenous origin, EVs have been widely explored as next-generation nanoscale drug delivery systems, allowing them to circumvent certain drawbacks associated with existing therapies (143). The impact of obesity on the biological components of ADEVs from different cell origins has been described previously (144). Therefore, the critical function of ADEVs and the role of ADEVs and their cargoes in multiple diseases were emphasized here.

The present review summarizes the composition and function of ADEVs derived from different cell sources in ATs, such as adipocytes, preadipocytes, macrophages, and MSCs. In addition, ADEVs participate in developing pathologies associated with metabolic diseases, CVDs, and several types of cancer (Table I). Understanding the mechanisms behind the effects of ADEVs on obesity or metabolic disorders and CVDs may contribute to the development of novel therapeutic strategies. However, the vast majority of current research is currently in the early stages, and no definitive marker of ADEV has yet been identified, complicating the isolation of ADEVs from ATs with high purity. In current research models, ADEVs from different sources are frequently derived from in vitro cell cultures. Therefore, further investigation is required to reveal the detailed characteristics of ADEVs.

Table I.

Summary of ADEV cargos and their functions in recipient cells.

Table I.

Summary of ADEV cargos and their functions in recipient cells.

A, ADEVs in metabolic disorders

Adipose tissue-EVsN.D.Promote M1 polarization of macrophages; Induce IR(102)
Adipocyte-EVsmiR-34aInhibit M2 polarization of macrophages(103)
Human adipocyte-EVsMIF, M-CSF, TNF-αPromote M1 polarization of macrophages(86)
ATM-EVsmiR-155Reduce the insulin sensitivity in adipocytes, the liver, and the muscle(91)
Adipocyte-EVsmiR-27aInduce hepatic and skeletal muscle IR(105,107)
ATM-EVsmiR-29aInduce IR in adipocytes, myocytes, and hepatocytes(81)
WAT-EVsmiR-222Promote IR in the liver and skeletal muscle(106)
Human adipocyte-EVsmiR-20b-5pImpair insulin action in skeletal muscle(110)

B, ADEVs and CVDs

OriginCargo Functions(Refs.)

VAT-EVsN.D.Facilitate macrophage foam cell generation and exacerbate atherosclerosis(116)
Adipocyte-EVsmiRNAsIncrease macrophage cholesterol efflux(117)
3T3-L1-EVsmiR-802-5pPromote insulin resistance in cardiomyocytes(119)
Adipocyte-EVsN.D.Impair the function of vascular endothelial cells(121)
Adipocyte-EVsN.D.Promote the attachment of leukocytes to endothelial cells(122)
Adipocyte-EVsmiR-200aImpair the function of cardiomyocytes, and promote the process of cardiac hypertrophy(123)
Adipocyte-EVsmiR-130b-3pExacerbate ischemic heart injury(124)

C, ADEVs in cancer

OriginCargo Functions(Refs.)

Adipocyte-EVsMMP3Promote lung tumor metastasis(128)
ADMSC-EVsN.D.Promote the invasion, migration, and proliferation of osteosarcoma cells(129)
ADSC-EVsAngiogenic proteinsPromote the tube-like formation of endothelial cells(130)
ADMSC-EVsN.D.Promote the metastasis of breast cancer cells(131)
Adipocyte-EVsFA substrates, proteins implicated in FAOPromote lung tumor metastasis(90)
Adipocyte-EVsFAO enzyme, FA substratesTrigger metabolic remodeling, facilitate FAO and tumor aggressiveness(78)

[i] N.D., not detected; ADEVs, adipose tissue-derived extracellular vesicles; ATM, adipose tissue macrophage; WAT, white adipose tissue; VAT, visceral adipose tissue; ADSC, adipose tissue-derived stem cells; ADMSC, adipose tissue-derived mesenchymal stem cells; FAO, fatty acid oxidation; FA, fatty acids; miR/miRNA, microRNA; IR, insulin resistance; MIF, macrophage migration inhibitory factor; M-CSF, macrophage colony stimulating factor 1; TNF-α, tumor necrosis factor-α; MMP3, matrix metallopeptidase 3.


Not applicable.


This work was supported by the National Natural Science Foundation of China (grant no. 82000003), the Natural Science Foundation of Zhejiang Province, China (grant no. LY23HO60009), the Natural Science Foundation of Zhejiang Province, China (grant no. LGF20H040009), and the China Postdoctoral Science Foundation (grant no. 2020M671748).

Availability of data and materials

Not applicable.

Authors' contributions

XBY, JYH, and JL wrote the manuscript. XHK and XLL conceived the subject of review and edited the manuscript. XHK designed and created the schematic representations. Data authentication is not applicable. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.





extracellular vesicles


adipose tissue-derived extracellular vesicles


type 2 diabetes


cardiovascular disease


Alzheimer's disease


cardiac hypertrophy


white adipose tissues


brown adipose tissues


beige adipose tissues




intraluminal vesicles


multivesicular bodies


noncoding RNAs




subcutaneous ATs


dermal WATs


visceral ATs


adipose tissue-derived stem cells


adipose tissue macrophages


insulin resistance


glucose transporter 4


peroxisome proliferator-activated receptor


fatty acids


fatty acid oxidation



Mohammed MS, Sendra S, Lloret J and Bosch I: Systems and WBANs for Controlling Obesity. J Healthc Eng. 2018:15647482018. View Article : Google Scholar : PubMed/NCBI


Kusminski CM, Bickel PE and Scherer PE: Targeting adipose tissue in the treatment of obesity-associated diabetes. Nat Rev Drug Discov. 15:639–660. 2016. View Article : Google Scholar : PubMed/NCBI


Abu-Farha M, Al-Mulla F, Thanaraj TA, Kavalakatt S, Ali H, Abdul Ghani M and Abubaker J: Impact of Diabetes in Patients Diagnosed With COVID-19. Front Immunol. 11:5768182020. View Article : Google Scholar : PubMed/NCBI


Goodman KE, Magder LS, Baghdadi JD, Pineles L, Levine AR, Perencevich EN and Harris AD: Impact of sex and metabolic comorbidities on coronavirus disease 2019 (COVID-19) mortality risk across age groups: 66 646 inpatients across 613 U.S. Hospitals. Clin Infect Dis. 73:e4113–e4123. 2021. View Article : Google Scholar : PubMed/NCBI


Piroth L, Cottenet J, Mariet AS, Bonniaud P, Blot M, Tubert-Bitter P and Quantin C: Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: A nationwide, population-based retrospective cohort study. Lancet Respir Med. 9:251–259. 2021. View Article : Google Scholar : PubMed/NCBI


Ottaviani E, Malagoli D and Franceschi C: The evolution of the adipose tissue: A neglected enigma. Gen Comp Endocrinol. 174:1–4. 2011. View Article : Google Scholar : PubMed/NCBI


Unamuno X, Gomez-Ambrosi J, Rodriguez A, Becerril S, Fruhbeck G and Catalan V: Adipokine dysregulation and adipose tissue inflammation in human obesity. Eur J Clin Invest. 48:e129972018. View Article : Google Scholar : PubMed/NCBI


Burhans MS, Hagman DK, Kuzma JN, Schmidt KA and Kratz M: Contribution of adipose tissue inflammation to the development of type 2 diabetes Mellitus. Compr Physiol. 9:1–58. 2018. View Article : Google Scholar : PubMed/NCBI


Berg AH, Combs TP, Du X, Brownlee M and Scherer PE: The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med. 7:947–953. 2001. View Article : Google Scholar : PubMed/NCBI


Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, et al: Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 423:762–769. 2003. View Article : Google Scholar : PubMed/NCBI


Hefetz-Sela S and Scherer PE: Adipocytes: Impact on tumor growth and potential sites for therapeutic intervention. Pharmacol Ther. 138:197–210. 2013. View Article : Google Scholar : PubMed/NCBI


Igata M, Motoshima H, Tsuruzoe K, Kojima K, Matsumura T, Kondo T, Taguchi T, Nakamaru K, Yano M, Kukidome D, et al: Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression. Circ Res. 97:837–844. 2005. View Article : Google Scholar : PubMed/NCBI


Douros JD, Baltzegar DA, Reading BJ, Seale AP, Lerner DT, Grau EG and Borski RJ: Leptin stimulates cellular glycolysis through a STAT3 dependent mechanism in Tilapia. Front Endocrinol (Lausanne). 9:4652018. View Article : Google Scholar : PubMed/NCBI


Huang Z and Xu A: Adipose extracellular vesicles in intercellular and inter-organ crosstalk in metabolic health and diseases. Front Immunol. 12:6086802021. View Article : Google Scholar : PubMed/NCBI


Padilla J, Vieira-Potter VJ, Jia G and Sowers JR: Role of perivascular adipose tissue on vascular reactive oxygen species in type 2 diabetes: A give-and-take relationship. Diabetes. 64:1904–1906. 2015. View Article : Google Scholar : PubMed/NCBI


Kern PA, Ranganathan S, Li C, Wood L and Ranganathan G: Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 280:E745–E751. 2001. View Article : Google Scholar : PubMed/NCBI


Keller S, Sanderson MP, Stoeck A and Altevogt P: Exosomes: From biogenesis and secretion to biological function. Immunol Lett. 107:102–108. 2006. View Article : Google Scholar : PubMed/NCBI


Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M, Wolfrum C, Rao TN, Winnay JN, Garcia-Martin R, Grinspoon SK, et al: Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 542:450–455. 2017. View Article : Google Scholar : PubMed/NCBI


Rome S, Blandin A and Le Lay S: Adipocyte-Derived extracellular vesicles: State of the art. Int J Mol Sci. 22:17882021. View Article : Google Scholar : PubMed/NCBI


Vidal M: Exosomes: Revisiting their role as ‘garbage bags’. Traffic. 20:815–828. 2019. View Article : Google Scholar : PubMed/NCBI


van der Pol E, Boing AN, Harrison P, Sturk A and Nieuwland R: Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev. 64:676–705. 2012. View Article : Google Scholar : PubMed/NCBI


Tricarico C, Clancy J and D'Souza-Schorey C: Biology and biogenesis of shed microvesicles. Small GTPases. 8:220–232. 2017. View Article : Google Scholar : PubMed/NCBI


Cai H, Reinisch K and Ferro-Novick S: Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle. Dev Cell. 12:671–682. 2007. View Article : Google Scholar : PubMed/NCBI


Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O and Geuze HJ: Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem. 273:20121–20127. 1998. View Article : Google Scholar : PubMed/NCBI


Giebel B and Helmbrecht C: Methods to Analyze EVs. Methods Mol Biol. 1545:1–20. 2017. View Article : Google Scholar : PubMed/NCBI


Wolf P: The nature and significance of platelet products in human plasma. Br J Haematol. 13:269–288. 1967. View Article : Google Scholar : PubMed/NCBI


Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A and Rak J: Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol. 10:619–624. 2008. View Article : Google Scholar : PubMed/NCBI


Harding C, Heuser J and Stahl P: Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: Demonstration of a pathway for receptor shedding. Eur J Cell Biol. 35:256–263. 1984.PubMed/NCBI


Pan BT, Teng K, Wu C, Adam M and Johnstone RM: Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol. 101:942–948. 1985. View Article : Google Scholar : PubMed/NCBI


Kalra H, Drummen GP and Mathivanan S: Focus on extracellular vesicles: Introducing the next small big thing. Int J Mol Sci. 17:1702016. View Article : Google Scholar : PubMed/NCBI


Minciacchi VR, Freeman MR and Di Vizio D: Extracellular vesicles in cancer: Exosomes, microvesicles and the emerging role of large oncosomes. Semin Cell Dev Biol. 40:41–51. 2015. View Article : Google Scholar : PubMed/NCBI


Raposo G and Stoorvogel W: Extracellular vesicles: Exosomes, microvesicles, and friends. J Cell Biol. 200:373–383. 2013. View Article : Google Scholar : PubMed/NCBI


Mulcahy LA, Pink RC and Carter DR: Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles. 3:2014. View Article : Google Scholar : PubMed/NCBI


Llorente A, Skotland T, Sylvanne T, Kauhanen D, Rog T, Orlowski A, Vattulainen I, Ekroos K and Sandvig K: Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim Biophys Acta. 1831:1302–1309. 2013. View Article : Google Scholar : PubMed/NCBI


Laulagnier K, Javalet C, Hemming FJ, Chivet M, Lachenal G, Blot B, Chatellard C and Sadoul R: Amyloid precursor protein products concentrate in a subset of exosomes specifically endocytosed by neurons. Cell Mol Life Sci. 75:757–773. 2018. View Article : Google Scholar : PubMed/NCBI


Vargas A, Zhou S, Ethier-Chiasson M, Flipo D, Lafond J, Gilbert C and Barbeau B: Syncytin proteins incorporated in placenta exosomes are important for cell uptake and show variation in abundance in serum exosomes from patients with preeclampsia. FASEB J. 28:3703–3719. 2014. View Article : Google Scholar : PubMed/NCBI


Kamerkar S, LeBleu VS, Sugimoto H, Yang S, Ruivo CF, Melo SA, Lee JJ and Kalluri R: Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature. 546:498–503. 2017. View Article : Google Scholar : PubMed/NCBI


van Niel G, D'Angelo G and Raposo G: Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 19:213–228. 2018. View Article : Google Scholar : PubMed/NCBI


Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q, Zimmerman LJ, Liebler DC, Ping J, Liu Q, Evans R, et al: Reassessment of exosome composition. Cell. 177:428–445. e182019. View Article : Google Scholar : PubMed/NCBI


Corrado C, Raimondo S, Saieva L, Flugy AM, De Leo G and Alessandro R: Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an interleukin 8-dependent survival of leukemia cells. Cancer Lett. 348:71–76. 2014. View Article : Google Scholar : PubMed/NCBI


Ailawadi S, Wang X, Gu H and Fan GC: Pathologic function and therapeutic potential of exosomes in cardiovascular disease. Biochim Biophys Acta. 1852:1–11. 2015. View Article : Google Scholar : PubMed/NCBI


van Marken Lichtenbelt W: Brown adipose tissue and the regulation of nonshivering thermogenesis. Curr Opin Clin Nutr Metab Care. 15:547–552. 2012. View Article : Google Scholar : PubMed/NCBI


Lee YH, Kim SN, Kwon HJ and Granneman JG: Metabolic heterogeneity of activated beige/brite adipocytes in inguinal adipose tissue. Sci Rep. 7:397942017. View Article : Google Scholar : PubMed/NCBI


Keipert S and Jastroch M: Brite/beige fat and UCP1 - is it thermogenesis? Biochim Biophys Acta. 1837:1075–1082. 2014. View Article : Google Scholar : PubMed/NCBI


Wang Z, Ning T, Song A, Rutter J, Wang QA and Jiang L: Chronic cold exposure enhances glucose oxidation in brown adipose tissue. EMBO Rep. 21:e500852020. View Article : Google Scholar : PubMed/NCBI


Shamsi BH, Ma C, Naqvi S and Xiao Y: Effects of pioglitazone mediated activation of PPAR-ү on CIDEC and obesity related changes in mice. PLoS One. 9:e1069922014. View Article : Google Scholar : PubMed/NCBI


Giampietro L, Gallorini M, De Filippis B, Amoroso R, Cataldi A and di Giacomo V: PPAR-ү agonist GL516 reduces oxidative stress and apoptosis occurrence in a rat astrocyte cell line. Neurochem Int. 126:239–245. 2019. View Article : Google Scholar : PubMed/NCBI


Jung SM, Sanchez-Gurmaches J and Guertin DA: Brown adipose tissue development and metabolism. Handb Exp Pharmacol. 251:3–36. 2019. View Article : Google Scholar : PubMed/NCBI


Lau P, Tuong ZK, Wang SC, Fitzsimmons RL, Goode JM, Thomas GP, Cowin GJ, Pearen MA, Mardon K, Stow JL and Muscat GE: Roralpha deficiency and decreased adiposity are associated with induction of thermogenic gene expression in subcutaneous white adipose and brown adipose tissue. Am J Physiol Endocrinol Metab. 308:E159–E171. 2015. View Article : Google Scholar : PubMed/NCBI


Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, et al: Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 150:366–376. 2012. View Article : Google Scholar : PubMed/NCBI


Ikeda K, Maretich P and Kajimura S: The common and distinct features of brown and beige adipocytes. Trends Endocrinol Metab. 29:191–200. 2018. View Article : Google Scholar : PubMed/NCBI


Pinckard KM and Stanford KI: The heartwarming effect of brown adipose tissue. Mol Pharmacol. 102:460–471. 2022. View Article : Google Scholar : PubMed/NCBI


Berbee JF, Boon MR, Khedoe PP, Bartelt A, Schlein C, Worthmann A, Kooijman S, Hoeke G, Mol IM, John C, et al: Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development. Nat Commun. 6:63562015. View Article : Google Scholar : PubMed/NCBI


Altshuler-Keylin S, Shinoda K, Hasegawa Y, Ikeda K, Hong H, Kang Q, Yang Y, Perera RM, Debnath J and Kajimura S: Beige adipocyte maintenance is regulated by autophagy-induced mitochondrial clearance. Cell Metab. 24:402–419. 2016. View Article : Google Scholar : PubMed/NCBI


Rosen ED and Spiegelman BM: Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 444:847–853. 2006. View Article : Google Scholar : PubMed/NCBI


Arner P: Regional adipocity in man. J Endocrinol. 155:191–192. 1997. View Article : Google Scholar : PubMed/NCBI


Chen SX, Zhang LJ and Gallo RL: Dermal white adipose tissue: A newly recognized layer of skin innate defense. J Invest Dermatol. 139:1002–1009. 2019. View Article : Google Scholar : PubMed/NCBI


Zhang LJ, Guerrero-Juarez CF, Hata T, Bapat SP, Ramos R, Plikus MV and Gallo RL: Innate immunity. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science. 347:67–71. 2015. View Article : Google Scholar : PubMed/NCBI


Fruhbeck G: Overview of adipose tissue and its role in obesity and metabolic disorders. Methods Mol Biol. 456:1–22. 2008. View Article : Google Scholar : PubMed/NCBI


Salvador J, Silva C, Pujante P and Fruhbeck G: Abdominal obesity: An indicator of cardiometabolic risk. Endocrinol Nutr. 55:420–432. 2008.(In English, Spanish). View Article : Google Scholar : PubMed/NCBI


Scheja L and Heeren J: The endocrine function of adipose tissues in health and cardiometabolic disease. Nat Rev Endocrinol. 15:507–524. 2019. View Article : Google Scholar : PubMed/NCBI


Stern JH, Rutkowski JM and Scherer PE: Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk. Cell Metab. 23:770–784. 2016. View Article : Google Scholar : PubMed/NCBI


Eto H, Suga H, Matsumoto D, Inoue K, Aoi N, Kato H, Araki J and Yoshimura K: Characterization of structure and cellular components of aspirated and excised adipose tissue. Plast Reconstr Surg. 124:1087–1097. 2009. View Article : Google Scholar : PubMed/NCBI


Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP and Hedrick MH: Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Eng. 7:211–228. 2001. View Article : Google Scholar : PubMed/NCBI


Brown JC, Shang H, Li Y, Yang N, Patel N and Katz AJ: Isolation of adipose-derived stromal vascular fraction cells using a novel point-of-care device: Cell characterization and review of the literature. Tissue Eng Part C Methods. 23:125–135. 2017. View Article : Google Scholar : PubMed/NCBI


Wu H and Ballantyne CM: Metabolic inflammation and insulin resistance in obesity. Circ Res. 126:1549–1564. 2020. View Article : Google Scholar : PubMed/NCBI


Hollenberg CH and Vost A: Regulation of DNA synthesis in fat cells and stromal elements from rat adipose tissue. J Clin Invest. 47:2485–2498. 1969. View Article : Google Scholar : PubMed/NCBI


Panina YA, Yakimov AS, Komleva YK, Morgun AV, Lopatina OL, Malinovskaya NA, Shuvaev AN, Salmin VV, Taranushenko TE and Salmina AB: Plasticity of adipose tissue-derived stem cells and regulation of angiogenesis. Front Physiol. 9:16562018. View Article : Google Scholar : PubMed/NCBI


Cao Y: Adipose tissue angiogenesis as a therapeutic target for obesity and metabolic diseases. Nat Rev Drug Discov. 9:107–115. 2010. View Article : Google Scholar : PubMed/NCBI


Mahlakoiv T, Flamar AL, Johnston LK, Moriyama S, Putzel GG, Bryce PJ and Artis D: Stromal cells maintain immune cell homeostasis in adipose tissue via production of interleukin-33. Sci Immunol. 4:eaax04162019. View Article : Google Scholar : PubMed/NCBI


Sun C, Berry WL and Olson LE: PDGFRα controls the balance of stromal and adipogenic cells during adipose tissue organogenesis. Development. 144:83–94. 2017. View Article : Google Scholar : PubMed/NCBI


Mclaughlin T, Ackerman SE, Shen L and Engleman E: Role of innate and adaptive immunity in obesity-associated metabolic disease. J Clin Invest. 127:5–13. 2017. View Article : Google Scholar : PubMed/NCBI


Rochette L, Mazini L, Malka G, Zeller M, Cottin Y and Vergely C: The crosstalk of adipose-derived stem cells (ADSC), oxidative stress, and inflammation in protective and adaptive responses. Int J Mol Sci. 21:92622020. View Article : Google Scholar : PubMed/NCBI


Hui X, Zhang M, Gu P, Li K, Gao Y, Wu D, Wang Y and Xu A: Adipocyte SIRT1 controls systemic insulin sensitivity by modulating macrophages in adipose tissue. EMBO Rep. 18:645–657. 2017. View Article : Google Scholar : PubMed/NCBI


Hotamisligil GS: Inflammation, metaflammation and immunometabolic disorders. Nature. 542:177–185. 2017. View Article : Google Scholar : PubMed/NCBI


Hotamisligil GS: Foundations of immunometabolism and implications for metabolic health and disease. Immunity. 47:406–420. 2017. View Article : Google Scholar : PubMed/NCBI


Man K, Kutyavin VI and Chawla A: Tissue immunometabolism: Development, physiology, and pathobiology. Cell Metab. 25:11–26. 2017. View Article : Google Scholar : PubMed/NCBI


Clement E, Lazar I, Attane C, Carrie L, Dauvillier S, Ducoux-Petit M, Esteve D, Menneteau T, Moutahir M, Le Gonidec S, et al: Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells. EMBO J. 39:e1025252020. View Article : Google Scholar : PubMed/NCBI


Hartwig S, De Filippo E, Goddeke S, Knebel B, Kotzka J, Al-Hasani H, Roden M, Lehr S and Sell H: Exosomal proteins constitute an essential part of the human adipose tissue secretome. Biochim Biophys Acta Proteins Proteom. 1867:1401722019. View Article : Google Scholar : PubMed/NCBI


Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ and Lotvall JO: Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 9:654–659. 2007. View Article : Google Scholar : PubMed/NCBI


Liu T, Sun YC, Cheng P and Shao HG: Adipose tissue macrophage-derived exosomal miR-29a regulates obesity-associated insulin resistance. Biochem Biophys Res Commun. 515:352–358. 2019. View Article : Google Scholar : PubMed/NCBI


Geng L, Lam K and Xu A: The therapeutic potential of FGF21 in metabolic diseases: From bench to clinic. Nat Rev Endocrinol. 16:654–667. 2020. View Article : Google Scholar : PubMed/NCBI


Gao J, Li X, Wang Y, Cao Y, Yao D, Sun L, Qin L, Qiu H and Zhan X: Adipocyte-derived extracellular vesicles modulate appetite and weight through mTOR signalling in the hypothalamus. Acta Physiol (Oxf). 228:e133392020. View Article : Google Scholar : PubMed/NCBI


Lee JE, Moon PG, Lee IK and Baek MC: Proteomic Analysis of extracellular vesicles released by adipocytes of otsuka long-evans tokushima fatty (OLETF) Rats. Protein J. 34:220–235. 2015. View Article : Google Scholar : PubMed/NCBI


Sano S, Izumi Y, Yamaguchi T, Yamazaki T, Tanaka M, Shiota M, Osada-Oka M, Nakamura Y, Wei M, Wanibuchi H, et al: Lipid synthesis is promoted by hypoxic adipocyte-derived exosomes in 3T3-L1 cells. Biochem Biophys Res Commun. 445:327–333. 2014. View Article : Google Scholar : PubMed/NCBI


Kranendonk ME, Visseren FL, van Balkom BW, Nolte-'t Hoen EN, van Herwaarden JA, de Jager W, Schipper HS, Brenkman AB, Verhaar MC, Wauben MH and Kalkhoven E: Human adipocyte extracellular vesicles in reciprocal signaling between adipocytes and macrophages. Obesity (Silver Spring). 22:1296–1308. 2014. View Article : Google Scholar : PubMed/NCBI


Phoonsawat W, Aoki-Yoshida A, Tsuruta T and Sonoyama K: Adiponectin is partially associated with exosomes in mouse serum. Biochem Biophys Res Commun. 448:261–266. 2014. View Article : Google Scholar : PubMed/NCBI


Crewe C and Scherer PE: Intercellular and interorgan crosstalk through adipocyte extracellular vesicles. Rev Endocr Metab Disord. 23:61–69. 2022. View Article : Google Scholar : PubMed/NCBI


Connolly KD, Wadey RM, Mathew D, Johnson E, Rees DA and James PE: Evidence for adipocyte-derived extracellular vesicles in the human circulation. Endocrinology. 159:3259–3267. 2018. View Article : Google Scholar : PubMed/NCBI


Lazar I, Clement E, Dauvillier S, Milhas D, Ducoux-Petit M, Legonidec S, Moro C, Soldan V, Dalle S, Balor S, et al: Adipocyte Exosomes Promote Melanoma Aggressiveness through Fatty Acid Oxidation: A Novel Mechanism Linking Obesity and Cancer. Cancer Res. 76:4051–4057. 2016. View Article : Google Scholar : PubMed/NCBI


Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A, Seo JB, Ofrecio JM, Wollam J, Hernandez-Carretero A, Fu W, et al: Adipose tissue macrophage-derived exosomal miRNAs Can modulate in vivo and in vitro insulin sensitivity. Cell. 171:372–384.e12. 2017. View Article : Google Scholar : PubMed/NCBI


Bassi EJ, Moraes-Vieira PM, Moreira-Sa CS, Almeida DC, Vieira LM, Cunha CS, Hiyane MI, Basso AS, Pacheco-Silva A and Camara NO: Immune regulatory properties of allogeneic adipose-derived mesenchymal stem cells in the treatment of experimental autoimmune diabetes. Diabetes. 61:2534–2545. 2012. View Article : Google Scholar : PubMed/NCBI


Mizuno H, Tobita M and Uysal AC: Concise review: Adipose-derived stem cells as a novel tool for future regenerative medicine. Stem Cells. 30:804–810. 2012. View Article : Google Scholar : PubMed/NCBI


Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D and Delgado M: Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology. 136:978–989. 2009. View Article : Google Scholar : PubMed/NCBI


Garcia-Contreras M, Vera-Donoso CD, Hernandez-Andreu JM, Garcia-Verdugo JM and Oltra E: Therapeutic potential of human adipose-derived stem cells (ADSCs) from cancer patients: A pilot study. PLoS One. 9:e1132882014. View Article : Google Scholar : PubMed/NCBI


Zhao H, Shang Q, Pan Z, Bai Y, Li Z, Zhang H, Zhang Q, Guo C, Zhang L and Wang Q: Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and beiging in white adipose tissue. Diabetes. 67:235–247. 2018. View Article : Google Scholar : PubMed/NCBI


Jung YJ, Kim HK, Cho Y, Choi JS, Woo CH, Lee KS, Sul JH, Lee CM, Han J, Park JH, et al: Cell reprogramming using extracellular vesicles from differentiating stem cells into white/beige adipocytes. Sci Adv. 6:eaay67212020. View Article : Google Scholar : PubMed/NCBI


Fuster JJ, Ouchi N, Gokce N and Walsh K: Obesity-Induced changes in adipose tissue microenvironment and their impact on cardiovascular disease. Circ Res. 118:1786–1807. 2016. View Article : Google Scholar : PubMed/NCBI


Zhao S, Kusminski CM and Scherer PE: Adiponectin, leptin and cardiovascular disorders. Circ Res. 128:136–149. 2021. View Article : Google Scholar : PubMed/NCBI


Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL and Ferrante AJ: CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest. 116:115–124. 2006. View Article : Google Scholar : PubMed/NCBI


Lumeng CN, Bodzin JL and Saltiel AR: Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 117:175–184. 2007. View Article : Google Scholar : PubMed/NCBI


Deng ZB, Poliakov A, Hardy RW, Clements R, Liu C, Liu Y, Wang J, Xiang X, Zhang S, Zhuang X, et al: Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes. 58:2498–2505. 2009. View Article : Google Scholar : PubMed/NCBI


Pan Y, Hui X, Hoo RLC, Ye D, Chan CYC, Feng T, Wang Y, Lam KSL and Xu A: Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation. J Clin Invest. 129:834–849. 2019. View Article : Google Scholar : PubMed/NCBI


James DE, Stockli J and Birnbaum MJ: The aetiology and molecular landscape of insulin resistance. Nat Rev Mol Cell Biol. 22:751–771. 2021. View Article : Google Scholar : PubMed/NCBI


Yu Y, Du H, Wei S, Feng L, Li J, Yao F, Zhang M, Hatch GM and Chen L: Adipocyte-Derived exosomal MiR-27a induces insulin resistance in skeletal muscle through repression of PPARү. Theranostics. 8:2171–2188. 2018. View Article : Google Scholar : PubMed/NCBI


Li D, Song H, Shuo L, Wang L, Xie P, Li W, Liu J, Tong Y, Zhang CY, Jiang X, et al: Gonadal white adipose tissue-derived exosomal MiR-222 promotes obesity-associated insulin resistance. Aging (Albany NY). 12:22719–22743. 2020.PubMed/NCBI


Kranendonk ME, Visseren FL, van Herwaarden JA, Nolte-'t Hoen EN, de Jager W, Wauben MH and Kalkhoven E: Effect of extracellular vesicles of human adipose tissue on insulin signaling in liver and muscle cells. Obesity (Silver Spring). 22:2216–2223. 2014. View Article : Google Scholar : PubMed/NCBI


Gao X, Salomon C and Freeman DJ: Extracellular vesicles from adipose tissue-A potential role in obesity and type 2 diabetes? Front Endocrinol (Lausanne). 8:2022017. View Article : Google Scholar : PubMed/NCBI


Eguchi A, Lazic M, Armando AM, Phillips SA, Katebian R, Maraka S, Quehenberger O, Sears DD and Feldstein AE: Circulating adipocyte-derived extracellular vesicles are novel markers of metabolic stress. J Mol Med (Berl). 94:1241–1253. 2016. View Article : Google Scholar : PubMed/NCBI


Katayama M, Wiklander OPB, Fritz T, Caidahl K, El-Andaloussi S, Zierath JR and Krook A: Circulating exosomal miR-20b-5p is elevated in type 2 diabetes and could impair insulin action in human skeletal muscle. Diabetes. 68:515–526. 2019. View Article : Google Scholar : PubMed/NCBI


Kranendonk ME, de Kleijn DP, Kalkhoven E, Kanhai DA, Uiterwaal CS, van der Graaf Y, Pasterkamp G and Visseren FL; SMART Study Group, : Extracellular vesicle markers in relation to obesity and metabolic complications in patients with manifest cardiovascular disease. Cardiovasc Diabetol. 13:372014. View Article : Google Scholar : PubMed/NCBI


Su S, Guntur AR, Nguyen DC, Fakory SS, Doucette CC, Leech C, Lotana H, Kelley M, Kohli J, Martino J, et al: A renewable source of human beige adipocytes for development of therapies to treat metabolic Syndrome. Cell Rep. 25:3215–3228,e9. 2018. View Article : Google Scholar : PubMed/NCBI


Connolly KD, Rees DA and James PE: Role of adipocyte-derived extracellular vesicles in vascular inflammation. Free Radic Biol Med. 172:58–64. 2021. View Article : Google Scholar : PubMed/NCBI


Dai W, Liu Z, Yang S and Kong J: Inflamed adipose tissue: Therapeutic Targets for obesity-related endothelial injury. Endocrinology. 164:bqad0942023. View Article : Google Scholar : PubMed/NCBI


Koenen M, Hill MA, Cohen P and Sowers JR: Obesity, adipose tissue and vascular dysfunction. Circ Res. 128:951–968. 2021. View Article : Google Scholar : PubMed/NCBI


Xie Z, Wang X, Liu X, Du H, Sun C, Shao X, Tian J, Gu X, Wang H, Tian J and Yu B: Adipose-Derived exosomes exert proatherogenic effects by regulating macrophage foam cell formation and polarization. J Am Heart Assoc. 7:e0074422018. View Article : Google Scholar : PubMed/NCBI


Barberio MD, Kasselman LJ, Playford MP, Epstein SB, Renna HA, Goldberg M, Deleon J, Voloshyna I, Barlev A, Salama M, et al: Cholesterol efflux alterations in adolescent obesity: Role of adipose-derived extracellular vesical microRNAs. J Transl Med. 17:2322019. View Article : Google Scholar : PubMed/NCBI


Fleury A, Martinez MC and Le Lay S: Extracellular vesicles as therapeutic tools in cardiovascular diseases. Front Immunol. 5:3702014. View Article : Google Scholar : PubMed/NCBI


Wen Z, Li J, Fu Y, Zheng Y, Ma M and Wang C: Hypertrophic adipocyte-derived exosomal miR-802-5p contributes to insulin resistance in cardiac myocytes through targeting hSP60. Obesity (Silver Spring). 28:1932–1940. 2020. View Article : Google Scholar : PubMed/NCBI


Monteiro JP, Bennett M, Rodor J, Caudrillier A, Ulitsky I and Baker AH: Endothelial function and dysfunction in the cardiovascular system: The long non-coding road. Cardiovasc Res. 115:1692–1704. 2019. View Article : Google Scholar : PubMed/NCBI


Muller G: Microvesicles/exosomes as potential novel biomarkers of metabolic diseases. Diabetes Metab Syndr Obes. 5:247–282. 2012. View Article : Google Scholar : PubMed/NCBI


Wadey RM, Connolly KD, Mathew D, Walters G, Rees DA and James PE: Inflammatory adipocyte-derived extracellular vesicles promote leukocyte attachment to vascular endothelial cells. Atherosclerosis. 283:19–27. 2019. View Article : Google Scholar : PubMed/NCBI


Fang X, Stroud MJ, Ouyang K, Fang L, Zhang J, Dalton ND, Gu Y, Wu T, Peterson KL, Huang HD, et al: Adipocyte-specific loss of PPARү attenuates cardiac hypertrophy. JCI Insight. 1:e899082016. View Article : Google Scholar : PubMed/NCBI


Gan L, Xie D, Liu J, Bond LW, Christopher TA, Lopez B, Zhang L, Gao E, Koch W, Ma XL and Wang Y: Small extracellular microvesicles mediated pathological communications between dysfunctional adipocytes and cardiomyocytes as a novel mechanism exacerbating ischemia/reperfusion injury in diabetic mice. Circulation. 141:968–983. 2020. View Article : Google Scholar : PubMed/NCBI


Parekh N, Chandran U and Bandera EV: Obesity in cancer survival. Annu Rev Nutr. 32:311–342. 2012. View Article : Google Scholar : PubMed/NCBI


Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, Wang YY, Meulle A, Salles B, Le Gonidec S, et al: Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. 71:2455–2465. 2011. View Article : Google Scholar : PubMed/NCBI


Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, et al: Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 17:1498–1503. 2011. View Article : Google Scholar : PubMed/NCBI


Wang J, Wu Y, Guo J, Fei X, Yu L and Ma S: Adipocyte-derived exosomes promote lung cancer metastasis by increasing MMP9 activity via transferring MMP3 to lung cancer cells. Oncotarget. 8:81880–81891. 2017. View Article : Google Scholar : PubMed/NCBI


Wang Y, Chu Y, Li K, Zhang G, Guo Z, Wu X, Qiu C, Li Y, Wan X, Sui J, et al: Exosomes secreted by adipose-derived mesenchymal stem cells foster metastasis and osteosarcoma proliferation by increasing COLGALT2 expression. Front Cell Dev Biol. 8:3532020. View Article : Google Scholar : PubMed/NCBI


Gangadaran P, Rajendran RL, Oh JM, Oh EJ, Hong CM, Chung HY, Lee J and Ahn BC: Identification of angiogenic cargo in extracellular vesicles secreted from human adipose tissue-derived stem cells and induction of angiogenesis in vitro and in vivo. Pharmaceutics. 13:4952021. View Article : Google Scholar : PubMed/NCBI


Khanh VC, Fukushige M, Moriguchi K, Yamashita T, Osaka M, Hiramatsu Y and Ohneda O: Type 2 diabetes mellitus induced paracrine effects on breast cancer metastasis through extracellular vesicles derived from human mesenchymal stem cells. Stem Cells Dev. 29:1382–1394. 2020. View Article : Google Scholar : PubMed/NCBI


Mattiske S, Suetani RJ, Neilsen PM and Callen DF: The oncogenic role of miR-155 in breast cancer. Cancer Epidemiol Biomarkers Prev. 21:1236–1243. 2012. View Article : Google Scholar : PubMed/NCBI


Balaban S, Shearer RF, Lee LS, van Geldermalsen M, Schreuder M, Shtein HC, Cairns R, Thomas KC, Fazakerley DJ, Grewal T, et al: Adipocyte lipolysis links obesity to breast cancer growth: Adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer Metab. 5:12017. View Article : Google Scholar : PubMed/NCBI


Kuo CY and Ann DK: When fats commit crimes: Fatty acid metabolism, cancer stemness and therapeutic resistance. Cancer Commun (Lond). 38:472018. View Article : Google Scholar : PubMed/NCBI


Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L, et al: Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther. 19:1769–1779. 2011. View Article : Google Scholar : PubMed/NCBI


Hardy J: Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci. 20:154–159. 1997. View Article : Google Scholar : PubMed/NCBI


Selkoe DJ: The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease. Trends Cell Biol. 8:447–453. 1998. View Article : Google Scholar : PubMed/NCBI


Katsuda T, Tsuchiya R, Kosaka N, Yoshioka Y, Takagaki K, Oki K, Takeshita F, Sakai Y, Kuroda M and Ochiya T: Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Sci Rep. 3:11972013. View Article : Google Scholar : PubMed/NCBI


Garcia-Contreras M and Thakor AS: Human adipose tissue-derived mesenchymal stem cells and their extracellular vesicles modulate lipopolysaccharide activated human microglia. Cell Death Discov. 7:982021. View Article : Google Scholar : PubMed/NCBI


Geng W, Tang H, Luo S, Lv Y, Liang D, Kang X and Hong W: Exosomes from miRNA-126-modified ADSCs promotes functional recovery after stroke in rats by improving neurogenesis and suppressing microglia activation. Am J Transl Res. 11:780–792. 2019.PubMed/NCBI


Jiang M, Wang H, Jin M, Yang X, Ji H, Jiang Y, Zhang H, Wu F, Wu G, Lai X, et al: Exosomes from MiR-30d-5p-ADSCs reverse acute ischemic stroke-induced, autophagy-mediated brain injury by promoting M2 microglial/macrophage polarization. Cell Physiol Biochem. 47:864–878. 2018. View Article : Google Scholar : PubMed/NCBI


Takahashi Y and Takakura Y: Extracellular vesicle-based therapeutics: Extracellular vesicles as therapeutic targets and agents. Pharmacol Ther. 242:1083522023. View Article : Google Scholar : PubMed/NCBI


Greening DW, Xu R, Ale A, Hagemeyer CE and Chen W: Extracellular vesicles as next generation immunotherapeutics. Semin Cancer Biol. 90:73–100. 2023. View Article : Google Scholar : PubMed/NCBI


Kwan HY, Chen M, Xu K and Chen B: The impact of obesity on adipocyte-derived extracellular vesicles. Cell Mol Life Sci. 78:7275–7288. 2021. View Article : Google Scholar : PubMed/NCBI

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Yang X, Hao J, Luo J, Lu X and Kong X: Adipose tissue‑derived extracellular vesicles: <br />Systemic messengers in health and disease (Review). Mol Med Rep 28: 189, 2023
Yang, X., Hao, J., Luo, J., Lu, X., & Kong, X. (2023). Adipose tissue‑derived extracellular vesicles: <br />Systemic messengers in health and disease (Review). Molecular Medicine Reports, 28, 189.
Yang, X., Hao, J., Luo, J., Lu, X., Kong, X."Adipose tissue‑derived extracellular vesicles: <br />Systemic messengers in health and disease (Review)". Molecular Medicine Reports 28.4 (2023): 189.
Yang, X., Hao, J., Luo, J., Lu, X., Kong, X."Adipose tissue‑derived extracellular vesicles: <br />Systemic messengers in health and disease (Review)". Molecular Medicine Reports 28, no. 4 (2023): 189.