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. 2016 Jan 18;49(1):3–13. doi: 10.1111/cpr.12233

Physiological and pathological impact of exosomes of adipose tissue

Yan Zhang 1,2,3, Mei Yu 1,2,✉, Weidong Tian 1,2,3,✉
PMCID: PMC6496788  PMID: 26776755

Abstract

Exosomes are nanovesicles that have emerged as a new intercellular communication system for transporting proteins and RNAs; recent studies have shown that they play a role in many physiological and pathological processes such as immune regulation, cell differentiation, infection and cancer. By transferring proteins, mRNAs and microRNAs, exosomes act as information vehicles that alter the behavior of recipient cells. Compared to direct cell‐cell contact or secreted factors, exosomes can affect recipient cells in more efficient ways. In whole adipose tissues, it has been shown that exosomes exist in supernatants of adipocytes and adipose stromal cells (ADSCs). Adipocyte exosomes are linked to lipid metabolism and obesity‐related insulin resistance and exosomes secreted by ADSCs are involved in angiogenesis, immunomodulation and tumor development. This review introduces characteristics of exosomes in adipose tissue, summarizes their functions in different physiological and pathological processes and provides the further insight into potential application of exosomes to disease diagnosis and treatment.

Introduction

Adipose tissue is composed of around 50% mature adipocytes as well as stromal cells such as adipose progenitor cells, preadipocytes, fibroblasts, immune cells, endothelial cells, and smooth muscle cells. Some studies 1 have emphasized that adipose tissue communicates systemically with other organs (brain, liver, skeletal muscle) and locally with other cells (preadipocytes, endothelial cells and monocytes/macrophages) through secreted products 2. For example, it has been shown that secretory factors from adipose tissue extract promotes angiogenesis and adipogenesis both in vitro and in vivo 3, 4. Moreover, the stromal‐vascular compartment of adipose tissue contains adipose‐derived mesenchymal stem cells (ADSCs) that can differentiate along different lineages in vitro and in vivo and secrete a large number of proteins with roles in angiogenesis, immunomodulation, wound healing and tissue regeneration 5.

In addition to secreting proteins, cells can also secret exosomes, a type of extracellular vesicle (EV) 6 which can modify and activate target cells via paracrine or endocrine signaling 7. Exosomes have been demonstrated to be a novel mode of cell communication for multiple physiological and pathological functions, including proliferation and differentiation 8, immunomodulation 9 and tumorigenesis 10. Furthermore, exosomes can be used as biomarkers for disease diagnosis 11, 12 and even as carriers to deliver drugs 13. By transferring proteins, mRNAs and microRNAs, exosomes act as vehicles of information that may alter behaviors of recipient cells 14.

The role of adipocyte and ADSC exosomes on physiology and pathology of adipose tissue is the focus of this article. Their potential application in diagnosing and treating certain diseases is also further discussed.

Characteristics of exosomes

It has been 30 years since Trams et al. found that various cells exfoliated vesicles with 5′‐nucleotidase activity and referred to them as exosomes 15. Sources of exosomes include such cells as reticulocytes 16, platelets 17, immunocytes 18, neurons 18, tumor cells 19 and mesenchymal stem cells (MSCs) 20, 21. Exosomes can also be isolated from body fluids such as serum 22, urine 23, saliva 24, semen 25 and cerebrospinal fluid 26. Depending on their orientation, exosomes can have cup shaped appearance when visualized by electron microscopy. They are in the order of 30–100 nm in size and have buoyant density in sucrose of 1.10–1.21 g/ml 18, 27, 28. It has been shown that size distribution of exosomes is not affected by different isolation methods but that their diameter may be altered with a change in state of the parent cells 29. For example, it has been reported that the diameter of exosomes from (all types of?)aaa cancer cells is different from that of normal cells 29, 30. Furthermore, there are several further EVs, such as microsomes, microvesicles, retrovirus‐like particles and apoptotic bodies 31, 32 whose diameters overlap with those of exosomes (Table 1). Therefore, vesicle size cannot be adopted to define or identify exosomes.

Table 1.

Comparison of extracellular vesicles

Extracellular vesicles Biogenesis Size Density Surface markers References
Exosomes Endocytosis and fusion with plasma membrane 30–100 nm 1.10–1.21 g/ml CD9,63, Alix 43, 44
Microsomes Fragments of endoplasmic reticulum 80–120 nm Average: 1.20 g/ml GRP78, PDI 45
Microvesicles Outward budding and fission of plasma membrane 50–2000 nm 1.25–1.30 g/ml ARF6, VCAMP3 32, 46
Retrovirus‐like particles Direct budding from the plasma membrane 90–100 nm 1.17 g/ml Gag 47, 48, 49
Apoptotic bodies Programmed cell death, disintegration of the cellular content 50–5000 nm 1.18–1.28 g/ml TSP, C3b 50
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Exosomes are about a 100‐fold enriched in tetraspanins compared to their parental cells 33, 34. CD9, CD63, CD81 or CD82 provide specially abundant exosomes and are often used for exosome biomarkering 19. However, that CD9 has also been detected in larger vesicles demonstrates the drawbacks of using tetraspanins to be exosome‐specific biomarkers 35. Exosome biogenesis related proteins (for example Alix, TSG101, Rab GTPases), heat shock proteins (HSP 60,70,90), cytoskeletal proteins (for example actin, tubulin, syntenin) and adhesion proteins [for example, milk fat globule‐EGF factor VIII (MFG‐E8)] are also included with exosomes 36, 37, 38. Abundance of lipid rafts is a further remarkable characteristic of exosomes. Exosomes have distinct membrane domains enriched in cholesterol and GM1 gangliosides, are similar in composition to plasma membrane rafts 39. In terms of RNAs, some RNAs of exosomes are expressed exclusively or at high levels compared to parent cells 40. Some reports have shown that exosomes include components of the RNA‐induced silencing complex which mediates miRNA targeting to mRNA 41. However, Chevillet et al. 42 discovered that even the most abundant miRNAs are present at far less than one copy per exosome, which suggests that most individual exosomes are unlikely to be functional in miRNA communication. Thus, further research is needed to uncover the role of miRNAs in exosome cell communication.

Exosome biogenesis

The mechanism of exosome biogenesis is distinctly different from that of other EVs 32. Formation of exosomes begins with invagination and endocytosis of the plasma membrane. Proteins involved in this process, such as tetraspanin, also play a role in regulation of cell development, signal activation, cell growth and motility 51. The endocytic vesicles are then transported to early endosomes, undergo a series of transformations such as acidification, then change in protein content, to become late endosomes. Finally, membranes of late endosomes bud into surrounding lumina to form the vesicles 30–100 nm in size, referred to as intraluminal vesicles or multivesicular bodies (MVBs) 32, 43, 52. There are two different fates for MVBs: they may be delivered to lysosomes for degradation, or can fuse with the plasma membrane. This latter process results in the secretion of exosomes 16, 53, 54, which requires formation of an endosomal sorting complex required for transport (ESCRT); depletion of different ESCRT components leads to reduction in secretion of the exosomes 55, 56. The ESCRT is made up of four complexes (ESCRT‐0, I, II, III) and associated proteins (VPS4, VTA1, ALIX). ESCRT‐0 is responsible for cargo clustering in a ubiquitin‐dependent manner, whereas ESCRT‐I and ESCRT‐II induce membrane deformation to form buds; ESCRT‐III drives vesicle excission. The accessory proteins (especially VPS4 ATPase) are involved in dissociation and recycling of ESCRT machinery 55, 56. In addition to ESCRT‐dependent pathways, tetraspanins also play a role in exosome biogenesis 57. Increased exosome secretion occurs in response to molecules such as p53 which respond to a variety of stress signals including genotoxic stress, hypoxia, and even expression of activated oncogenes 58, serotonin 53, platelet‐derived growth factor 59, amyloid plaques 60, GAIP interacting protein C terminus 61, and PARK9 62. Furthermore, increased exosome release can be triggered by several types of stress, such as changes in pH, hypoxia, oxidative stress, thermal change, shear stress, and radiation 19.

Adipose tissue exosomes

In vitro, existence of exosomes has been reported in culture medium of adipose tissues 63, adipocytes 64, 65 and ADSCs 20. Katsuda et al., by nanoparticle tracking analysis, found that ADSC‐derived exosomes had peak size distribution of 150–200 nm which was larger than previously reported 28. Although these diameters do not conform to the common standard for exosomes, markers such as CD63, HSP‐70 were positively expressed, thus indicating that the size range of exosomes may therefore vary depending on the particular cell type.

In terms of contents of exosomes, 231 proteins have been identified in 3T3‐L1 exosomes under normoxic and hypoxic culture conditions. Enzymes [fatty acid synthase (FASN), acetyl‐CoA carboxylase (ACC) and glucose‐6‐phosphate dehydrogenase (G6PD)] that could lead to fatty acid production have been reported in adipocyte‐derived exosomes 66. Exosomes from serum have been demonstrated to contain adiponectin and trace amounts of resistin 67. Given that adiponectin is produced exclusively by adipocytes, it is possible that adiponectin‐associated exosomes in serum are derived from adipocytes 2, 67. Adiponectin is an adipokine involved in glucose and lipid metabolism, fatty acid oxidation and insulin sensitivity 68. Thus adiponectin‐associated exosomes may influence metabolism of distant cells. In addition to adipocyte specific proteins, immunomodulatory proteins such as tumor necrosis factor alpha (TNF‐α), macrophage‐colony‐stimulating factor (MCSF), and retinol binding protein 4 (RBP‐4) have also been reported to be present in exosomes 69.

Ogawa et al. 64 analyzed mRNA profiles of adipocyte‐derived microvesicles (including exosomes) and found that mRNAs were involved in metabolic, cellular and immune processes. The mRNA data corresponded to protein results which indicated that mainly metabolic and cellular processes were involved 70. Some adipogenesis‐related gene transcripts (such as PPARγ2, adiponectin, leptin) were also found in exosomes derived from adipogenic induced 3T3‐L1 cells, and expression of these genes increased with length of time of induction 64.These exosomes contained abundant miRNA and some specific profiles were detected. For example, miRNAs that regulate adipogenesis such as miR‐103, miR‐146b, miR‐148a were prominently up‐regulated in adipocyte‐derived exosomes 71, 72, 73.

Functions of adipose tissue exosomes

Regulation of angiogenesis, proliferation and differentiation

Roles of exosomes in angiogenesis have been examined in several cell types, including endothelial cells, umbilical cord MSC, bone marrow MSC, cardiac progenitor cells and tumour cells 8, 74, 75 (Fig. 1a). There is evidence that MSC‐derived exosomes promote wound healing and muscle regeneration by enhancing cell proliferation and angiogenesis 76, 77. Exosomes induce angiogenesis by a variety of mechanisms, including activation of major intracellular kinase pathways, transference of pro‐angiogenic proteins and miRNAs, and inhibition of endothelial cell senescence 8. ADSCs, a component of adipose tissue, secrete membrane vesicles (including exosomes) which have been shown to promote vascular endothelial cell migration and proliferation and stimulate neo‐ vessel formation in an aortic ring assay 59, 78. The vesicles were internalized by microvascular endothelial cells and induced synthesis of matrix metalloproteinases (MMPs), which promoted invasion by endothelial cells 59. mRNAs and miRNAs expressed by exosomes also participate in regulation of angiogenesis‐related factors, such as hepatocyte growth‐factor, hairy and enhancer of split and T‐cell factor 79. These RNAs function as regulators of the Wnt and Notch signaling pathways, both involved in vascular development. However, in obesity angiogenic potential of exosomes may be impaired by reduced levels of angiogenic related factors such as vascular endothelial growth factor (VEGF), MMP‐2 and especially miR‐126 80. Reduction in miR‐126 levels leads to upregulation of Spred1 and inhibition of the Erk1/2 mitogen‐activated protein kinase (MAPK) pathway, which impairs angiogenic ability. In the field of tissue regeneration, survival of grafts requires sufficient vascularization in order to bring adequate supplies of nutrients and oxygen, and to drain the waste. Use of exosomes from ADSCs may have a bright future in this field.

Figure 1.

Figure 1

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Functions of ADSC exosomes. (a) To promote vascular endothelial cell proliferation, stimulate neovessel formation and induce MMP secretion, which can increase invasion of endothelial cells. (b) To protecte neurons from apoptosis, increase remyelination, and activate oligodendroglial precursors. (c) To inhibit differentiation of T cells into memory cells and secretion of IFN‐γ. (d) To stimulate tumour cells entering S and G2/M phases and enhance cell proliferation. Migrational ability of tumour cells may also be promoted.

Exosomes can also affect differentiation programs of MSCs by transferring miRNAs or proteins. For example, exosomes derived from neuronal cells promote neuronal differentiation of MSCs by delivering miR‐125b 81. Similarly, Eirin et al. 79 discovered that mRNAs (C/EBP‐α, KLF7) involved in adipogenesis are present in ADSC‐derived exosomes 82, 83. Adipocyte‐derived EVs with diameters similar to those of exosomes can deliver adipogenic mRNAs (PPARγ, leptin, C/EBP‐α and C/EBP‐δ) and anti‐osteoblastic miRNAs (miR‐138, miR‐30c, miR‐125a, miR‐125b, miR‐31) to osteoblasts 84. These factors reduce expression of two late osteoblastic differentiation markers, osteocalcin and osteopontin. Other proteins, for example MMPs ‐ which are involved in adipogenesis, and MFG‐E8 ‐ involved in angiogenesis, are found in exosomes 85, 86. Considering intimate relationships between angiogenesis and adipogenesis in adipose tissue regeneration, exosomes may have future applications in this field. Although pro‐adipogenetic factors are found in exosomes, so far there has been no evidence to show that exosomes can promote ADSCs to differentiate into mature adipocytes.

Besides their application in angiogenesis, exosomes also have roles in nerve regeneration (Fig. 1b). Low doses of ADSC‐derived exosomes significantly reduce vulnerability of neural cells to H2O2 by inhibiting the apoptotic cascade under conditions of oxidative stress damage and demyelination. In terms of neuroregeneration, exosomes increase the process of remyelination and activate formation of nestin‐positive oligodendroglial precursors 87. This indicates that ADSC‐derived exosomes can serve as factors to modulate the microenvironment in neuro‐inflammatory as well as in neurodegenerative disorders.

Regulation of immunity

Mesenchymal stem cells can regulate the immune response directly by cell‐to‐cell contact or by secretion of immunosuppressive factors (Fig. 1c). Exosomes contain many of these factors and have been shown to act in immunoregulation. Exosomes from ADSCs reduce proliferation rates of stimulated T lymphocytes in vitro. In the case of CD8+ T cells, exosomes significantly reduce percentages of terminally differentiated effector‐memory cells. Concerning CD4+ T cells, exosomes reduce percentages of effector‐memory cells and significantly increase percentages of central memory cells 88. Moreover, ADSC‐derived exosomes also inhibit T cell activation by reducing secretion of IFN‐γ 88. ADSC‐derived exosomes lack MHC class II and co‐stimulatory molecules, which indicate that these vesicles may have a direct inhibitory effect on activating T cells 88. Due to their immunomodulatory role, ADSC‐derived exosomes seem to reduce many risks and drawbacks that cell‐based therapies might bring, and so could be very useful in treatment of inflammation‐related diseases. Preclinical tests show that application of MSC‐derived exosomes have improved symptoms in graft‐versus‐host disease patients, for 5 months 89. However, effects of exosomes on the immune system remain controversial. Some reports suggest that ADSC‐derived exosomes fail to suppress lymphocyte proliferation 90.

Tumour exosomes

Adipose tissue plays a role in development of some tumors, specially those with which it has intimate relationships such as breast cancer and malignant melanoma. Adipocytes promote migration and epithelia‐to‐mesenchyme transition seen in breast cancers and malignant melanomas while ADSCs behave similarly in breast cancers 91, 92, 93. Parent cell type exosomes from adipose tissue play important parts in tumour growth (Fig. 1d). Those from BM‐MSCs inhibit tumour growth while exosomes from multiple myeloma BM‐MSCs exhibit multiple functions 94. Exosomes from human ADSCs have been reported to promote migration and proliferation of breast cancer cells and their global gene expression profile is altered, especially concerning the Wnt signaling pathway, by treatment with MSC‐exosomes 20, 95. Exosomes derived from pre‐adipocytes (3T3‐L1) promote tumourigenesis of breast cancer cells. In some reports, an antitumour compound (shikonin) increased levels of miR‐140 in 3T3‐L1‐derived exosomes and impacted ductal carcinoma cells in situ through the SOX9 signaling pathway 96. These results reveal the importance of signal transduction through exosomes in some tumour microenvironments. In glioblastoma, EVs (including exosomes) derived from ADSCs have been reported to stimulate cells to enter S and G2/M phase and enhance cancer cell proliferation, whereas MSC‐derived exosomes inhibited cancer cell proliferation and induced apoptosis 97. However, there is no evidence to show that exosomes from adipocytes have any impact on tumour cell migration, although this effect had been demonstrated for the parent cells. Altogether, exosomes may, in the future, provide novel therapeutic targets for tumour treatment.

Regulation of metabolism

Adipose tissue is a key organ that regulates energy metabolism, which it does by secreting factors such as adiponectin, TNF‐α and interleukin 6 (IL‐6), and by releasing exosomes 98. Release of exosomes from adipocytes is enhanced under the challenge of anti‐lipolytic and lipogenic signals, such as excess fatty acids (palmitate) and reactive oxygen species (H2O2), and by pharmacological agents 99. Large adipocytes are more efficient in production of microvesicles (including exosomes) loaded with CD73 and Gce1, two GPI‐anchored proteins involved in inhibition of lipolysis and stimulation of esterification. However, small adipocytes more readily accept these vesicles than do large ones, which would result in enlargement of lipid droplets and adipocyte size. In obesity, degree of insulin resistance is related to expansion of small adipocytes and reduction in expression of differentiation markers 100. The role exosomes play in this process provides us with a novel pharmacological target to control biogenesis of lipid droplets in obese insulin‐resistant patients. Furthermore, the environment influences secretion of exosomes. Hypoxia stimulates this in several cell types including breast cancer cells and ADSCs in a process that involves HIF‐1 101. In 3T3‐L1 cells, hypoxia has been shown to stimulate exosome secretion 3‐ to 4‐fold, increase production of lipogenic enzymes (such as ACC, G6PD, and FASN) and enhance volume of lipid droplets in adipocyte 66 (Fig. 2a). In obesity, levels of ACC, G6PD, FASN in exosomes also increases, which reflects metabolic stress in adipose tissue 66. Functions of exosomes in regulation of energy metabolism indicates that they are significantly effective in communication between adipocytes 102.

Figure 2.

Figure 2

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Roles of exosomes in obesity‐related diseases. (a) Exosomes taken in by small adipocytes result in enlargement of lipid droplets. In hypoxia, exosomes increase production of lipogenic enzymes (such as FASN, G6PD, ACC) and the size of lipid droplets. (b) Exosomes from obese individuals' adipose tissue activates monocyte differentiation into macrophages and prompts secretion of inflamation factors IL‐6 and TNF‐α, resulting in insulin resistance in adipocytes and liver. (c) Exosomes from obese individuals' adipocytes increase secretion of tissue inhibitor of metalloproteinases 1 (TIMP‐1) and plasminogen activator inhibitor‐1 (PAI‐1) promoting liver fibrogenesis. (d) Exosomes released from dysfunctional and hypertrophic adipocytes impaire function of vascular endothelial cells, indicating the functions of exosomes in development of obesity‐linked complications.

Obesity

Obesity, a chronic condition related to excessive increase in adipose tissue, has been considered to be a risk in development of insulin resistance, inflammation, hypertension, cardiovascular diseases and metabolic disorders 103. It has been demonstrated that release of factors that influence insulin sensitivity can be promoted in adipocytes through interactions with peritoneal macrophages. Large numbers of these cells infiltrate into adipose tissue in obese individuals and provoke systemic inflammation and insulin resistance 104. One recent study has demonstrated the role of exosomes in this process (Fig. 2b). Monocytes were shown to take up exosomes from obese adipose tissue, then differentiate into activated macrophages 63. Both pro‐inflammation (M1) and anti‐inflammation (M2) macrophage phenotypes were induced by adipose tissue‐derived exosomes. RBP4 in these exosomes activated macrophages to secrete higher quantities of MCSF, IL‐6 and TNF‐α through the TLR4/NF‐κB pathway. Secretion of IL‐6 and TNF‐α impaired insulin stimulation by reducing IRS‐1 and GLUT‐4 translocation. However, these data suggested that exosomes with abundant adiponectin induced higher release of insulin resistance cytokines (IL‐6, TNF‐α). This indicates that adipocyte‐derived exosomes were the main immunomodulatory effectors of secretion of insulin resistance factors 69. In addition to those released by macrophages, insulin resistance cytokines [IL‐6, monocyte chemoattractant protein‐1 (MCP‐1)] were also detected in the adipose tissue‐derived exosomes. Degree of insulin‐stimulated AKT phosphorylation has been associated with concentration of insulin‐resistant adipokines in liver and muscle cells when cultured with exosomes in vitro. Higher concentration of adipokines with insulin‐resistant properties [IL‐6, macrophage migration inhibitory factor (MIF), MCP‐1] in exosomes is related to inhibition of Akt 105. However, this effect was more pronounced in hepatocytes than in muscle cells. Thus, it can be concluded that insulin resistance is not related to cytokines the exosomes carried nor to activation of macrophages by the exosomes. Moreover, it is difficult to explain why, in some cases, insulin stimulating effects rather than insulin resistance effects were found in hepatocytes treated with exosomes 105.

miRNA profiles of exosomes from obese and lean individuals' visceral adipose tissue are different. Various miRNAs are involved in the transforming growth factor β (TGF‐β) and Wnt/β‐catenin signaling pathways, which play important roles in development of chronic inflammation as well as in inhibition of adipogenic differentiation of ADSCs 106, 107, 108. Compared to lean individulas' visceral exosomes, miR‐148b and miR‐4269 were found to be significantly downregulated in obese individulas' exosomes, while miR‐23b and miR‐4429 were upregulated 108. Both of these altered miRNAs target mRNAs in the TGF‐β and Wnt/β‐catenin signaling pathways. In the liver, it has been demonstrated that exosomes from obese individulas' visceral adipose tissue may affect formation of non‐alcoholic fatty liver disease 65 (Fig. 2c). The TGF‐β pathway has been the predicted target of these different miRNAs 65. Adipocyte exosomes activated the TGF‐β pathway and increased expression of proteins which inhibit extracellular matrix degradation, such as TIMP‐1, MMP‐7 and PAI‐1 109, 110. This results in accumulation of extracellular matrix and disrupts liver architecture.

Exosomes released from dysfunctional and hypertrophic adipocytes impair the function of vascular endothelial cells, which draws attention to their function in development of obesity‐linked complications 111, 112 (Fig. 2d). In obesity, inflammation of adipose tissues increases migration of monocytes. Exosomes from monocytes can adhere to endothelial cells and penetrate them, and can disrupt the integrity of the epithelia (ECs), resulting in apoptosis and increased cell surface thrombogenicity 113.

Diagnostic and therapeutic potential of exosomes

Metabolic diseases

In obesity, production of cystatin C and CD14, both of which are associated with development of cardiovascular complaints, is high in adipose tissues 114. Coincidentally, cystatin C and CD14 included in plasma EVs, are also altered in obese patients 115. One cohort study has indicated increase in cystatin C and CD14 in EVs (including exosomes) to be related to increased risk for myocardial infarction, vascular disease mortality and further vascular events, in patients with clinically manifest vascular disease 115. A further report describes the relationship between these EV markers and metabolic complications of obesity. Cystatin C expression in plasma EVs has been positively related to low‐grade systemic inflammation, low HDL‐cholesterol levels and metabolic syndrome, while CD14 expression was negatively related to adipose tissue abundance, dyslipidaemia and reduced risk for development of type 2 diabetes 112. These data indicate that changes in EV (including exosome) content reflects the condition of obesity‐related diseases and that exosomes in plasma may serve as a potential marker for prediction, diagnosis, prognosis, and therapy of metabolic diseases.

It has been reported that adipose fatty acid binding protein (aP2) regulates intracellular lipid trafficking in diverse tissues, through a non‐classical pathway in response to adipocyte lipase activity 116. Level of aP2 in exosomes significantly increases when lipolysis is stimulated. In obesity, adipose tissue becomes resistant to insulin‐mediated suppression of lipolysis which increases secretion of aP2 and leads to increased liver glucose output and diabetes 116. Given that lipase inhibitors have been suggested as tools for inhibiting toxic effects of lipids in metabolic disease, targeting the aP2‐associated secretory pathway may provide a novel way for treating metabolic diseases 116.

Neurodegenerative diseases

ADSC‐derived exosomes can influence accumulation of β‐amyloid peptide, which contributes to Alzheimer's disease. Neprilysin, an important enzyme that degrades the β‐amyloid (Aβ) peptide, is present in exosomes secreted from ADSCs. Both secreted and intracellular Aβ peptide levels were lower in mouse neuroblastoma N2a cells when cultured with exosomes 28. These cells had more pronounced effects on Aβ peptide levels than bone marrow‐derived MSCs; this highlights the therapeutic potential of ADSC‐derived exosomes in treating Alzheimer's disease 117. In contrast to MSC‐based therapy, use of ADSC exosomes has neither vascular obstructive effect nor other apparent adverse consequences 118. Although the clinical role of MSC‐derived exosomes has been reported to improve organ dysfunction and inhibit tumour growth 119, there are few reports focusing on therapeutic potentials of exosomes derived from ADSCs or adipose tissue.

Conclusions and prospects

Exosomes, as important means of cell communication, participate in a series physiological processes such as cell metabolism, proliferation and differentiation. On the other hand, they are also involved in development of obesity‐related diseases such as diabetes and angiocardiopathy. Exosomes from adipose tissue may be candidates for diagnosis and treatment, and studies on those from adipose tissues may help further understanding of the mechanisms of metabolic diseases. Furthermore, wide distribution and easy availability of adipose tissue has contributed to its significance in the fields of tissue regeneration and cosmetology and their use may improve adipocyte viability and growth due to their potential for pro‐adipogenesis and angiogenesis. However, many questions regarding application of exosomes remain to be addressed. For example, due to the complex composition of adipose tissue, cell type responsible for functional exosomes is not clear. Much information concerning the functional role of exosomes has been demonstrated using cultured cells, however, further in vivo investigations are needed to expand our understanding of exosomes.

Acknowledgments

We thank Prof. Graham P. Côté (Queen's University, Canada) for critical reading of the manuscript. This work was supported by Nature Science Foundation of China (81300848 and 30973348) and Key Technology R&D Program of Sichuan Province (2012JY0077).

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