Exosome-Mediated Impact on Systemic Metabolism

Literature Cited

1. 1.

   György B, Szabó TG, Pásztói M, Pál Z, Misják P et al. 2011. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell. Mol. Life Sci. 68:162667
   [Google Scholar]
2. 2.

   Couch Y, Buzàs EI, Di Vizio D, Gho YS, Harrison P et al. 2021. A brief history of nearly EV-erything—the rise and rise of extracellular vesicles. J. Extracell. Vesicles 10:14e12144
   [Google Scholar]
3. 3.

   Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. 2007. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9:6654–59
   [Google Scholar]
4. 4.

   van Niel G, Carter DRF, Clayton A, Lambert DW, Raposo G, Vader P. 2022. Challenges and directions in studying cell-cell communication by extracellular vesicles. Nat. Rev. Mol. Cell Biol. 23:5369–82
   [Google Scholar]
5. 5.

   Mathieu M, Martin-Jaular L, Lavieu G, Théry C. 2019. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat. Cell Biol. 21:19–17
   [Google Scholar]
6. 6.

   Gill S, Catchpole R, Forterre P. 2019. Extracellular membrane vesicles in the three domains of life and beyond. FEMS Microbiol. Rev. 43:3273–303
   [Google Scholar]
7. 7.

   Buzas EI. 2022. The roles of extracellular vesicles in the immune system. Nat. Rev. Immunol. 23:4236–50
   [Google Scholar]
8. 8.

   Verweij FJ, Balaj L, Boulanger CM, Carter DRF, Compeer EB et al. 2021. The power of imaging to understand extracellular vesicle biology in vivo. Nat. Methods 18:91013–26
   [Google Scholar]
9. 9.

   Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD et al. 2018. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 7:11535750
   [Google Scholar]
10. 10.

    Babst M. 2011. MVB vesicle formation: ESCRT-dependent, ESCRT-independent and everything in between. Curr. Opin. Cell Biol. 23:4452–57
    [Google Scholar]
11. 11.

    Henne WM, Buchkovich NJ, Emr SD. 2011. The ESCRT pathway. Dev. Cell 21:177–91
    [Google Scholar]
12. 12.

    McCullough J, Fisher RD, Whitby FG, Sundquist WI, Hill CP. 2008. ALIX-CHMP4 interactions in the human ESCRT pathway. PNAS 105:227687–91
    [Google Scholar]
13. 13.

    Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G et al. 2012. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 14:7677–85
    [Google Scholar]
14. 14.

    Pashkova N, Yu L, Schnicker NJ, Tseng C-C, Gakhar L et al. 2021. Interactions of ubiquitin and CHMP5 with the V domain of HD-PTP reveals role for regulation of Vps4 ATPase. Mol. Biol. Cell 32:22ar42
    [Google Scholar]
15. 15.

    Larios J, Mercier V, Roux A, Gruenberg J. 2020. ALIX- and ESCRT-III-dependent sorting of tetraspanins to exosomes. J. Cell Biol. 219:3e201904113
    [Google Scholar]
16. 16.

    Stuffers S, Sem Wegner C, Stenmark H, Brech A. 2009. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 10:7925–37
    [Google Scholar]
17. 17.

    Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D et al. 2008. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:58671244–47
    [Google Scholar]
18. 18.

    Perez-Hernandez D, Gutiérrez-Vázquez C, Jorge I, López-Martín S, Ursa A et al. 2013. The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. J. Biol. Chem. 288:1711649–61
    [Google Scholar]
19. 19.

    Villarroya-Beltri C, Baixauli F, Mittelbrunn M, Fernández-Delgado I, Torralba D et al. 2016. ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins. Nat. Commun. 7:13588
    [Google Scholar]
20. 20.

    Vanlandingham PA, Ceresa BP. 2009. Rab7 regulates late endocytic trafficking downstream of multivesicular body biogenesis and cargo sequestration. J. Biol. Chem. 284:1812110
    [Google Scholar]
21. 21.

    Mittelbrunn M, Vicente-Manzanares M, Sánchez-Madrid F. 2015. Organizing polarized delivery of exosomes at synapses. Traffic 16:4327–37
    [Google Scholar]
22. 22.

    Kang M, Jordan V, Blenkiron C, Chamley LW. 2021. Biodistribution of extracellular vesicles following administration into animals: a systematic review. J. Extracell. Vesicles 10:8e12085
    [Google Scholar]
23. 23.

    Liou W, Geuze HJ, Geelen MJH, Slot JW. 1997. The autophagic and endocytic pathways converge at the nascent autophagic vacuoles. J. Cell Biol. 136:161–70
    [Google Scholar]
24. 24.

    Baixauli F, López-Otín C, Mittelbrunn M. 2014. Exosomes and autophagy: coordinated mechanisms for the maintenance of cellular fitness. Front. Immunol. 5:403
    [Google Scholar]
25. 25.

    Zhao YG, Codogno P, Zhang H. 2021. Machinery, regulation and pathophysiological implications of autophagosome maturation. Nat. Rev. Mol. Cell Biol. 22:11733–50
    [Google Scholar]
26. 26.

    Sobo-Vujanovic A, Munich S, Vujanovic NL. 2014. Dendritic-cell exosomes cross-present Toll-like receptor-ligands and activate bystander dendritic cells. Cell. Immunol. 289:1–2119–27
    [Google Scholar]
27. 27.

    Théry C, Zitvogel L, Amigorena S. 2002. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2:8569–79
    [Google Scholar]
28. 28.

    Muntasell A, Berger AC, Roche PA. 2007. T cell-induced secretion of MHC class II-peptide complexes on B cell exosomes. EMBO J. 26:4263–72
    [Google Scholar]
29. 29.

    Kaksonen M, Roux A. 2018. Mechanisms of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell Biol. 19:5313–26
    [Google Scholar]
30. 30.

    Lajoie P, Nabi IR. 2010. Lipid rafts, caveolae, and their endocytosis. Int. Rev. Cell Mol. Biol. 282:C135–63
    [Google Scholar]
31. 31.

    Koike S, Jahn R. 2019. SNAREs define targeting specificity of trafficking vesicles by combinatorial interaction with tethering factors. Nat. Commun. 10:1608
    [Google Scholar]
32. 32.

    Fanaei M, Monk PN, Partridge LJ. 2011. The role of tetraspanins in fusion. Biochem. Soc. Trans. 39:2524–28
    [Google Scholar]
33. 33.

    Fitzner D, Schnaars M, Van Rossum D, Krishnamoorthy G, Dibaj P et al. 2011. Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J. Cell Sci. 124:Part 3447–58
    [Google Scholar]
34. 34.

    Costa Verdera H, Gitz-Francois JJ, Schiffelers RM, Vader P. 2017. Cellular uptake of extracellular vesicles is mediated by clathrin-independent endocytosis and macropinocytosis. J. Control. Release 266:100–8
    [Google Scholar]
35. 35.

    Horibe S, Tanahashi T, Kawauchi S, Murakami Y, Rikitake Y. 2018. Mechanism of recipient cell-dependent differences in exosome uptake. BMC Cancer 18:47
    [Google Scholar]
36. 36.

    Feng D, Zhao WL, Ye YY, Bai XC, Liu RQ et al. 2010. Cellular internalization of exosomes occurs through phagocytosis. Traffic 11:5675–87
    [Google Scholar]
37. 37.

    Lin XP, Mintern JD, Gleeson PA. 2020. Macropinocytosis in different cell types: similarities and differences. Membranes 10:8177
    [Google Scholar]
38. 38.

    Parolini I, Federici C, Raggi C, Lugini L, Palleschi S et al. 2009. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J. Biol. Chem. 284:4934211–22
    [Google Scholar]
39. 39.

    Joshi BS, de Beer MA, Giepmans BNG, Zuhorn IS. 2020. Endocytosis of extracellular vesicles and release of their cargo from endosomes. ACS Nano 14:44444–55
    [Google Scholar]
40. 40.

    Nakase I, Ueno N, Matsuzawa M, Noguchi K, Hirano M et al. 2021. Environmental pH stress influences cellular secretion and uptake of extracellular vesicles. FEBS Open Bio 11:3753–67
    [Google Scholar]
41. 41.

    O'Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. 2020. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat. Rev. Mol. Cell Biol. 21:10585–606
    [Google Scholar]
42. 42.

    Van den Brande S, Gijbels M, Wynant N, Santos D, Mingels L et al. 2018. The presence of extracellular microRNAs in the media of cultured Drosophila cells. Sci. Rep. 8:17312
    [Google Scholar]
43. 43.

    Lunavat TR, Cheng L, Kim DK, Bhadury J, Jang SC et al. 2015. Small RNA deep sequencing discriminates subsets of extracellular vesicles released by melanoma cells—evidence of unique microRNA cargos. RNA Biol. 12:8810
    [Google Scholar]
44. 44.

    Garcia-Martin R, Wang G, Brandão BB, Zanotto TM, Shah S et al. 2022. MicroRNA sequence codes for small extracellular vesicle release and cellular retention. Nature 601:7893446–51
    [Google Scholar]
45. 45.

    Bartel DP. 2018. Metazoan microRNAs. Cell 173:120–51
    [Google Scholar]
46. 46.

    Treiber T, Treiber N, Meister G. 2018. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat. Rev. Mol. Cell Biol. 20:5–20
    [Google Scholar]
47. 47.

    Groot M, Lee H. 2020. Sorting mechanisms for microRNAs into extracellular vesicles and their associated diseases. Cells 9:41044
    [Google Scholar]
48. 48.

    Iavello A, Frech VSL, Gai C, Deregibus MC, Quesenberry PJ, Camussi G. 2016. Role of Alix in miRNA packaging during extracellular vesicle biogenesis. Int. J. Mol. Med. 37:4958–66
    [Google Scholar]
49. 49.

    Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T. 2010. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 285:2317442
    [Google Scholar]
50. 50.

    Wei J, Lv L, Wan Y, Cao Y, Li G et al. 2015. Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells. Hepatology 61:41284–94
    [Google Scholar]
51. 51.

    O'Grady T, Njock MS, Lion M, Bruyr J, Mariavelle E et al. 2022. Sorting and packaging of RNA into extracellular vesicles shape intracellular transcript levels. BMC Biol. 20:72
    [Google Scholar]
52. 52.

    Temoche-Diaz MM, Shurtleff MJ, Nottingham RM, Yao J, Fadadu RP et al. 2019. Distinct mechanisms of microRNA sorting into cancer cell-derived extracellular vesicle subtypes. eLife 8:e47544
    [Google Scholar]
53. 53.

    Wozniak AL, Adams A, King KE, Dunn W, Christenson LK et al. 2020. The RNA binding protein FMR1 controls selective exosomal miRNA cargo loading during inflammation. J. Cell Biol. 219:10e201912074
    [Google Scholar]
54. 54.

    Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F, Pérez-Hernández D, Vázquez J et al. 2013. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat. Commun. 4:2980
    [Google Scholar]
55. 55.

    Wu B, Su S, Patil DP, Liu H, Gan J et al. 2018. Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1. Nat. Commun. 9:420
    [Google Scholar]
56. 56.

    Yin M, Cheng M, Liu C, Wu K, Xiong W et al. 2021. HNRNPA2B1 as a trigger of RNA switch modulates the miRNA-mediated regulation of CDK6. iScience 24:11103345
    [Google Scholar]
57. 57.

    Santangelo L, Giurato G, Cicchini C, Montaldo C, Mancone C et al. 2016. The RNA-binding protein SYNCRIP is a component of the hepatocyte exosomal machinery controlling microRNA sorting. Cell Rep. 17:3799–808
    [Google Scholar]
58. 58.

    Shurtleff MJ, Temoche-Diaz MM, Karfilis KV, Ri S, Schekman R. 2016. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. eLife 5:e19276
    [Google Scholar]
59. 59.

    Lin F, Zeng Z, Song Y, Li L, Wu Z et al. 2019. YBX-1 mediated sorting of miR-133 into hypoxia/reoxygenation-induced EPC-derived exosomes to increase fibroblast angiogenesis and MEndoT. Stem Cell Res. Ther. 10:263
    [Google Scholar]
60. 60.

    Yanshina DD, Kossinova OA, Gopanenko AV, Krasheninina OA, Malygin AA et al. 2018. Structural features of the interaction of the 3′-untranslated region of mRNA containing exosomal RNA-specific motifs with YB-1, a potential mediator of mRNA sorting. Biochimie 144:134–43
    [Google Scholar]
61. 61.

    Ying W, Riopel M, Bandyopadhyay G, Dong Y, Birmingham A et al. 2017. Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity. Cell 171:2372–84.e12
    [Google Scholar]
62. 62.

    Ji Y, Luo Z, Gao H, Dos Reis FCG, Bandyopadhyay G et al. 2021. Hepatocyte-derived exosomes from early onset obese mice promote insulin sensitivity through miR-3075. Nat. Metab. 3:91163–74
    [Google Scholar]
63. 63.

    Thomou T, Mori MA, Dreyfuss JM, Konishi M, Sakaguchi M et al. 2017. Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature 542:7642450–55
    [Google Scholar]
64. 64.

    Bhome R, Del Vecchio F, Lee GH, Bullock MD, Primrose JN et al. 2018. Exosomal microRNAs (exomiRs): small molecules with a big role in cancer. Cancer Lett. 420:228–35
    [Google Scholar]
65. 65.

    Yáñez-Mó M, R-M Siljander P, Andreu Z, Bedina Zavec A, Borràs FE et al. 2015. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 4:27066
    [Google Scholar]
66. 66.

    Mias GI, Veziroglu EM. 2020. Characterizing extracellular vesicles and their diverse RNA contents. Front. Genet. 11:700
    [Google Scholar]
67. 67.

    Zhang F, Ma D, Zhao W, Wang D, Liu T et al. 2020. Obesity-induced overexpression of miR-802 impairs insulin transcription and secretion. Nat. Commun. 11:1822
    [Google Scholar]
68. 68.

    Thomson DW, Bracken CP, Goodall GJ. 2011. Experimental strategies for microRNA target identification. Nucleic Acids Res. 39:166845–53
    [Google Scholar]
69. 69.

    Lin C, Miles WO. 2019. Survey and summary Beyond CLIP: advances and opportunities to measure RBP-RNA and RNA-RNA interactions. Nucleic Acids Res. 47:115490–5501
    [Google Scholar]
70. 70.

    Kim S, Kim S, Chang HR, Kim D, Park J et al. 2021. The regulatory impact of RNA-binding proteins on microRNA targeting. Nat. Commun. 12:5057
    [Google Scholar]
71. 71.

    Funcke J-B, Scherer PE. 2019. Thematic review series: adipose biology beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication. J. Lipid Res. 60:101648–84
    [Google Scholar]
72. 72.

    Lee YS, Olefsky J. 2021. Chronic tissue inflammation and metabolic disease. Genes Dev. 35:5–6307–28
    [Google Scholar]
73. 73.

    Saltiel AR. 2021. Insulin signaling in health and disease. J. Clin. Investig. 131:e142241
    [Google Scholar]
74. 74.

    Rohm TV, Meier DT, Olefsky JM, Donath MY. 2022. Inflammation in obesity, diabetes, and related disorders. Immunity 55:31–55
    [Google Scholar]
75. 75.

    Kahn CR, Wang G, Lee KY. 2019. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. J. Clin. Investig. 129:103990–4000
    [Google Scholar]
76. 76.

    Sakers A, De Siqueira MK, Seale P, Villanueva CJ. 2022. Leading edge adipose-tissue plasticity in health and disease. Cell 185:419–46
    [Google Scholar]
77. 77.

    Connolly KD, Wadey RM, Mathew D, Johnson E, Rees DA, James PE. 2018. Evidence for adipocyte-derived extracellular vesicles in the human circulation. Endocrinology 159:93259–67
    [Google Scholar]
78. 78.

    Dang S-Y, Leng Y, Wang Z-X, Xiao X, Zhang X et al. 2019. Exosomal transfer of obesity adipose tissue for decreased miR-141-3p mediate insulin resistance of hepatocytes. Int. J. Biol. Sci. 15:2351–68
    [Google Scholar]
79. 79.

    Pan Y, Hui X, Chong Hoo RL, Ye D, Cheung Chan CY et al. 2019. Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation. J. Clin. Investig. 129:2834–49
    [Google Scholar]
80. 80.

    Kita S, Maeda N, Shimomura I. 2019. Interorgan communication by exosomes, adipose tissue, and adiponectin in metabolic syndrome. J. Clin. Investig. 129:104041–49
    [Google Scholar]
81. 81.

    Zhang Y, Shi L, Mei H, Zhang J, Zhu Y et al. 2015. Inflamed macrophage microvesicles induce insulin resistance in human adipocytes. Nutr. Metab. 12:21
    [Google Scholar]
82. 82.

    Kranendonk MEG, Visseren FLJ, Van Herwaarden JA, Nolte-’t Hoen ENM, de Jager W et al. 2014. Effect of extracellular vesicles of human adipose tissue on insulin signaling in liver and muscle cells. Obesity 22:102216–23
    [Google Scholar]
83. 83.

    Deng Z, Poliakov A, Hardy RW, Clements R, Liu C et al. 2009. Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes 58:112498–505
    [Google Scholar]
84. 84.

    Ferrante SC, Nadler EP, Pillai DK, Hubal MJ, Wang Z et al. 2015. Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease. Pediatr. Res. 77:3447–54
    [Google Scholar]
85. 85.

    Eguchi A, Mulya A, Lazic M, Radhakrishnan D, Berk MP et al. 2015. Microparticles release by adipocytes act as “find-me” signals to promote macrophage migration. PLOS ONE 10:4e0123110
    [Google Scholar]
86. 86.

    Müller G, Schneider M, Biemer-Daub G, Wied S. 2011. Microvesicles released from rat adipocytes and harboring glycosylphosphatidylinositol-anchored proteins transfer RNA stimulating lipid synthesis. Cell Signal. 23:71207–23
    [Google Scholar]
87. 87.

    Crewe C, Funcke JB, Li S, Joffin N, Gliniak CM et al. 2021. Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes. Cell Metab 33:91853
    [Google Scholar]
88. 88.

    Li C, Menoret A, Farragher C, Ouyang Z, Bonin C et al. 2019. Single-cell transcriptomics-based MacSpectrum reveals macrophage activation signatures in diseases. JCI Insight 5:10e126453
    [Google Scholar]
89. 89.

    Xiong X, Kuang H, Ansari S, Liu T, Gong J et al. 2019. Landscape of intercellular crosstalk in healthy and NASH liver revealed by single-cell secretome gene analysis. Mol. Cell 75:3644–60.e5
    [Google Scholar]
90. 90.

    Jaitin DA, Adlung L, Thaiss CA, Weiner A, Li B et al. 2019. Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner. Cell 178:3686–98.e14
    [Google Scholar]
91. 91.

    Russo L, Lumeng CN. 2018. Properties and functions of adipose tissue macrophages in obesity. Immunology 155:4407–17
    [Google Scholar]
92. 92.

    Fuchs A, Samovski D, Smith GI, Cifarelli V, Farabi SS et al. 2021. Associations among adipose tissue immunology, inflammation and exosomes and insulin sensitivity in people with obesity and nonalcoholic fatty liver disease. Gastroenterology 161:3968–81.e12
    [Google Scholar]
93. 93.

    Liu T, Sun YC, Cheng P, Shao HG. 2019. Adipose tissue macrophage-derived exosomal miR-29a regulates obesity-associated insulin resistance. Biochem. Biophys. Res. Commun. 515:2352–58
    [Google Scholar]
94. 94.

    Ying W, Gao H, Dos Reis FCG, Bandyopadhyay G, Ofrecio JM et al. 2021. MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice. Cell Metab. 33:4781–90.e5
    [Google Scholar]
95. 95.

    De Silva N, Samblas M, Martínez JA, Milagro FI. 2018. Effects of exosomes from LPS-activated macrophages on adipocyte gene expression, differentiation, and insulin-dependent glucose uptake. J. Physiol. Biochem. 74:4559–68
    [Google Scholar]
96. 96.

    Chen L, Yao X, Yao H, Ji Q, Ding G, Liu X 2020. Exosomal miR-103-3p from LPS-activated THP-1 macrophage contributes to the activation of hepatic stellate cells. FASEB J. 34:45178–92
    [Google Scholar]
97. 97.

    Castaño C, Kalko S, Novials A, Párrizas M. 2018. Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice. PNAS 115:4812158–63
    [Google Scholar]
98. 98.

    Li G, Liu H, Ma C, Chen Y, Wang J, Yang Y. 2019. Exosomes are the novel players involved in the beneficial effects of exercise on type 2 diabetes. J. Cell Physiol. 234:914896–905
    [Google Scholar]
99. 99.

    Guescini M, Guidolin D, Vallorani L, Casadei L, Gioacchini AM et al. 2010. C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction. Exp. Cell Res. 316:121977–84
    [Google Scholar]
100. 100.

     Safdar A, Tarnopolsky MA. 2018. Exosomes as mediators of the systemic adaptations to endurance exercise. Cold Spring Harb. Perspect. Med. 8:3a029827
     [Google Scholar]
101. 101.

     Safdar A, Saleem A, Tarnopolsky MA. 2016. The potential of endurance exercise-derived exosomes to treat metabolic diseases. Nat. Rev. Endocrinol. 12:9504–17
     [Google Scholar]
102. 102.

     Bertoldi K, Cechinel LR, Schallenberger B, Corssac GB, Davies S et al. 2018. Circulating extracellular vesicles in the aging process: impact of aerobic exercise. Mol. Cell. Biochem. 440:1–2115–25
     [Google Scholar]
103. 103.

     Wu CX, Liu ZF. 2018. Proteomic profiling of sweat exosome suggests its involvement in skin immunity. J. Investig. Dermatol. 138:189–97
     [Google Scholar]
104. 104.

     Rong S, Wang L, Peng Z, Liao Y, Li D et al. 2020. The mechanisms and treatments for sarcopenia: could exosomes be a perspective research strategy in the future?. J. Cachexia Sarcopenia Muscle 11:2348–65
     [Google Scholar]
105. 105.

     Aswad H, Forterre A, Wiklander OPB, Vial G, Danty-Berger E et al. 2014. Exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice. Diabetologia 57:102155–64
     [Google Scholar]
106. 106.

     Combes V, Simon AC, Grau GE, Arnoux D, Camoin L et al. 1999. In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. J. Clin. Investig. 104:193–102
     [Google Scholar]
107. 107.

     Markiewicz M, Richard E, Marks N, Ludwicka-Bradley A. 2013. Impact of endothelial microparticles on coagulation, inflammation, and angiogenesis in age-related vascular diseases. J. Aging Res. 2013:734509
     [Google Scholar]
108. 108.

     Buesing KL, Densmore JC, Kaul S, Pritchard KA, Jarzembowski JA et al. 2011. Endothelial microparticles induce inflammation in acute lung injury. J. Surg. Res. 166:132–39
     [Google Scholar]
109. 109.

     Brodsky SV, Zhang F, Nasjletti A, Goligorsky MS. 2004. Endothelium-derived microparticles impair endothelial function in vitro. Am. J. Physiol. Heart. Circ. Physiol. 286:5H1910–15
     [Google Scholar]
110. 110.

     Liu Y, Huang W, Zhang R, Wu J, Li L, Tang Y. 2013. Proteomic analysis of TNF-α-activated endothelial cells and endothelial microparticles. Mol. Med. Rep. 7:1318–26
     [Google Scholar]
111. 111.

     Yamamoto S, Niida S, Azuma E, Yanagibashi T, Muramatsu M et al. 2015. Inflammation-induced endothelial cell-derived extracellular vesicles modulate the cellular status of pericytes. Sci. Rep. 5:8505
     [Google Scholar]
112. 112.

     Crewe C, Joffin N, Rutkowski JM, Kim M, Zhang F et al. 2018. An endothelial-to-adipocyte extracellular vesicle axis governed by metabolic state. Cell 175:3695–708.e13
     [Google Scholar]
113. 113.

     Chen J, Chen J, Cheng Y, Fu Y, Zhao H et al. 2020. Mesenchymal stem cell-derived exosomes protect beta cells against hypoxia-induced apoptosis via miR-21 by alleviating ER stress and inhibiting p38 MAPK phosphorylation. Stem Cell Res. Ther. 11:197
     [Google Scholar]
114. 114.

     Gesmundo I, Pardini B, Gargantini E, Gamba G, Birolo G et al. 2021. Adipocyte-derived extracellular vesicles regulate survival and function of pancreatic β cells. JCI Insight 6:5e141962
     [Google Scholar]
115. 115.

     Qian B, Yang Y, Tang N, Wang J, Sun P et al. 2021. M1 macrophage-derived exosomes impair beta cell insulin secretion via miR-212-5p by targeting SIRT2 and inhibiting Akt/GSK-3β/β-catenin pathway in mice. Diabetologia 64:92037–51
     [Google Scholar]
116. 116.

     Sun Y, Zhou Y, Shi Y, Zhang Y, Liu K et al. 2021. Expression of miRNA-29 in pancreatic β cells promotes inflammation and diabetes via TRAF3. Cell Rep. 34:108576
     [Google Scholar]
117. 117.

     Kulaj K, Harger A, Bauer M, Caliskan ÖS, Gupta TK et al. 2023. Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo. Nat. Commun. 14:709
     [Google Scholar]
118. 118.

     Jalabert A, Vial G, Guay C, Wiklander OPB, Nordin JZ et al. 2016. Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice. Diabetologia 59:51049–58
     [Google Scholar]
119. 119.

     Li J, Zhang Y, Ye Y, Li D, Liu Y et al. 2021. Pancreatic β cells control glucose homeostasis via the secretion of exosomal miR-29 family. J. Extracell. Vesicles 10:3e12055
     [Google Scholar]
120. 120.

     Lakhter AJ, Pratt RE, Moore RE, Doucette KK, Maier BF et al. 2018. Beta cell extracellular vesicle miR-21-5p cargo is increased in response to inflammatory cytokines and serves as a biomarker of type 1 diabetes. Diabetologia 61:51124–34
     [Google Scholar]
121. 121.

     Lazarus JV, Mark HE, Anstee QM, Arab JP, Batterham RL et al. 2021. Advancing the global public health agenda for NAFLD: a consensus statement. Nat. Rev. Gastroenterol. Hepatol. 19:60–78
     [Google Scholar]
122. 122.

     Huby T, Gautier EL. 2021. Immune cell-mediated features of non-alcoholic steatohepatitis. Nat. Rev. Immunol. 22:7429–43
     [Google Scholar]
123. 123.

     Szabo G, Momen-Heravi F. 2017. Extracellular vesicles in liver disease. Nat. Rev. Gastroenterol. Hepatol. 14:8455
     [Google Scholar]
124. 124.

     Povero D, Panera N, Eguchi A, Johnson CD, Papouchado BG et al. 2015. Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cells via microRNA targeting peroxisome proliferator-activated receptor-γ. Cell. Mol. Gastroenterol. Hepatol. 1:6646–63
     [Google Scholar]
125. 125.

     Ibrahim SH, Hirsova P, Tomita K, Bronk SF, Werneburg NW et al. 2016. Mixed lineage kinase 3 mediates release of C-X-C motif ligand 10-bearing chemotactic extracellular vesicles from lipotoxic hepatocytes. Hepatology 63:3731–44
     [Google Scholar]
126. 126.

     Hirsova P, Ibrahim SH, Krishnan A, Verma VK, Bronk SF et al. 2016. Lipid-induced signaling causes release of inflammatory extracellular vesicles from hepatocytes. Gastroenterology 150:4956
     [Google Scholar]
127. 127.

     Lee YS, Kim SY, Ko E, Lee JH, Yi HS et al. 2017. Exosomes derived from palmitic acid-treated hepatocytes induce fibrotic activation of hepatic stellate cells. Sci. Rep. 7:3710
     [Google Scholar]
128. 128.

     Jiang F, Chen Q, Wang W, Ling Y, Yan Y, Xia P. 2020. Hepatocyte-derived extracellular vesicles promote endothelial inflammation and atherogenesis via microRNA-1. J. Hepatol. 72:1156–66
     [Google Scholar]
129. 129.

     Kakazu E, Mauer AS, Yin M, Malhi H. 2016. Hepatocytes release ceramide-enriched pro-inflammatory extracellular vesicles in an IRE1α-dependent manner. J. Lipid Res. 57:2233–45
     [Google Scholar]
130. 130.

     Hirsova P, Gores GJ. 2015. Death receptor-mediated cell death and proinflammatory signaling in nonalcoholic steatohepatitis. Cell. Mol. Gastroenterol. Hepatol. 1:117
     [Google Scholar]
131. 131.

     Wang R, Ding Q, Yaqoob U, De Assuncao TDM, Verma VK et al. 2015. Exosome adherence and internalization by hepatic stellate cells triggers sphingosine 1-phosphate-dependent migration. J. Biol. Chem. 290:5230684–96
     [Google Scholar]
132. 132.

     Liu B, Wang J, Wang G, Jiang W, Li Z et al. 2023. Hepatocyte-derived exosomes deliver H2AFJ to hepatic stellate cells and promote liver fibrosis via the MAPK/STMN1 axis activation. Int. Immunopharmacol. 115:109605
     [Google Scholar]
133. 133.

     Gao H, Jin Z, Bandyopadhyay G, Wang G, Zhang D et al. 2022. Aberrant iron distribution via hepatocyte-stellate cell axis drives liver lipogenesis and fibrosis. Cell Metab. 34:81201–13.e5
     [Google Scholar]
134. 134.

     Liu X, Tan S, Liu H, Jiang J, Wang X et al. 2023. Hepatocyte-derived MASP1-enriched small extracellular vesicles activate HSCs to promote liver fibrosis. Hepatology 77:41181–97
     [Google Scholar]
135. 135.

     Charrier A, Chen R, Chen L, Kemper S, Hattori T et al. 2014. Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue growth factor (CCN2) between hepatic stellate cells, the principal fibrotic cells in the liver. Surgery 156:3548–55
     [Google Scholar]
136. 136.

     Gao J, Wei B, de Assuncao TM, Liu Z, Hu X et al. 2020. Hepatic stellate cell autophagy inhibits extracellular vesicle release to attenuate liver fibrosis. J. Hepatol. 73:51144–54
     [Google Scholar]
137. 137.

     Bruno S, Pasquino C, Herrera Sanchez MB, Tapparo M, Figliolini F al. 2020. HLSC-derived extracellular vesicles attenuate liver fibrosis and inflammation in a murine model of non-alcoholic steatohepatitis. Mol. Ther. 28:2479–89
     [Google Scholar]
138. 138.

     Zhang H, Ma Y, Cheng X, Wu D, Huang X et al. 2021. Targeting epigenetically maladapted vascular niche alleviates liver fibrosis in nonalcoholic steatohepatitis. Sci. Transl. Med. 13:614eabd1206
     [Google Scholar]
139. 139.

     Gao H, Jin Z, Bandyopadhyay G, Cunha e Rocha K, Liu X et al. 2022. MiR-690 treatment causes decreased fibrosis and steatosis and restores specific Kupffer cell functions in NASH. Cell Metab 34:7978–90
     [Google Scholar]
140. 140.

     Yao J-M, Ying H-Z, Zhang H-H, Qiu F-S, Wu J-Q, Yu C-H. 2023. Exosomal RBP4 potentiated hepatic lipid accumulation and inflammation in high-fat-diet-fed mice by promoting M1 polarization of Kupffer cells. Free Radic. Biol. Med. 195:58–73
     [Google Scholar]
141. 141.

     Inzaugarat ME, Wree A, Feldstein AE. 2016. Hepatocyte mitochondrial DNA released in microparticles and toll-like receptor 9 activation: a link between lipotoxicity and inflammation during nonalcoholic steatohepatitis. Hepatology 64:2669–71
     [Google Scholar]
142. 142.

     Zhao Y, Zhao M-F, Jiang S, Wu J, Liu J et al. 2020. Liver governs adipose remodelling via extracellular vesicles in response to lipid overload. Nat. Commun. 11:719
     [Google Scholar]
143. 143.

     Jung JW, Kim JE, Kim E, Lee H, Lee H et al. 2022. Liver-originated small extracellular vesicles with TM4SF5 target brown adipose tissue for homeostatic glucose clearance. J. Extracell. Vesicles 11:9e12262
     [Google Scholar]
144. 144.

     Arenaza L, Medrano M, Amasene M, Rodríguez-Vigil B, Díez I et al. 2017. Prevention of diabetes in overweight/obese children through a family based intervention program including supervised exercise (PREDIKID project): study protocol for a randomized controlled trial. Trials 18:1372
     [Google Scholar]
145. 145.

     Shi M-M, Yang Q-Y, Monsel A, Yan J-Y, Dai C-X et al. 2021. Preclinical efficacy and clinical safety of clinical-grade nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles. J. Extracell. Vesicles 10:10e12134
     [Google Scholar]
146. 146.

     Zhu Y-G, Shi M-M, Monsel A, Dai C-X, Dong X et al. 2022. Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study. Stem Cell Res. Ther. 13:220
     [Google Scholar]
147. 147.

     Kordelas L, Rebmann V, Ludwig A-K, Radtke S, Ruesing J et al. 2014. MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease. Leukemia 28:4970–73
     [Google Scholar]
148. 148.

     Nassar W, El-Ansary M, Sabry D, Mostafa MA, Fayad T et al. 2016. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater. Res. 20:21
     [Google Scholar]
149. 149.

     Täubel J, Hauke W, Rump S, Viereck J, Batkai S et al. 2021. Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study. Eur. Heart. J. 42:2178–88
     [Google Scholar]
150. 150.

     Herrmann IK, Wood MJA, Fuhrmann G. 2021. Extracellular vesicles as a next-generation drug delivery platform. Nat. Nanotechnol. 16:7748–59
     [Google Scholar]
151. 151.

     Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJA. 2011. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29:4341–45
     [Google Scholar]
152. 152.

     Yang J, Zhang X, Chen X, Wang L, Yang G. 2017. Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia. Mol. Ther. Nucleic Acids 7:278–87
     [Google Scholar]
153. 153.

     Kooijmans SAA, Aleza CG, Roffler SR, van Solinge WW, Vader P, Schiffelers RM. 2016. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting. J. Extracell. Vesicles 5:31053
     [Google Scholar]
154. 154.

     Pi F, Binzel DW, Lee TJ, Li Z, Sun M et al. 2018. Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression. Nat. Nanotechnol. 13:182–89
     [Google Scholar]
155. 155.

     Kamerkar S, LeBleu VS, Sugimoto H, Yang S, Ruivo CF et al. 2017. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 546:7659498–503
     [Google Scholar]
156. 156.

     Yim N, Ryu S-W, Choi K, Lee KR, Lee S et al. 2016. Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein-protein interaction module. Nat. Commun. 7:12277
     [Google Scholar]
157. 157.

     Choi H, Kim Y, Mirzaaghasi A, Heo J, Kim YN et al. 2020. Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality. Sci. Adv. 6:15eaaz6980
     [Google Scholar]
158. 158.

     Sheller-Miller S, Radnaa E, Yoo J-K, Choi K, Kim Y et al. 2021. Exosomal delivery of NF-κB inhibitor delays LPS-induced preterm birth and modulates fetal immune cell profile in mouse models. Sci. Adv. 7:4eabd3865
     [Google Scholar]
159. 159.

     Kim S, Lee SA, Yoon H, Kim MY, Yoo J-K et al. 2021. Exosome-based delivery of super-repressor IκBα ameliorates kidney ischemia-reperfusion injury. Kidney Int 100:3570–84
     [Google Scholar]
160. 160.

     Jang SC, Economides KD, Moniz RJ, Sia CL, Lewis N et al. 2021. ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance. Commun. Biol. 4:1497
     [Google Scholar]
161. 161.

     Oses M, Sanchez JM, Portillo MP, Aguilera CM, Labayen I. 2019. Circulating miRNAs as biomarkers of obesity and obesity-associated comorbidities in children and adolescents: a systematic review. Nutrients 11:122890
     [Google Scholar]
162. 162.

     Lischka J, Schanzer A, Hojreh A, Ba-Ssalamah A, de Gier C et al. 2021. Circulating microRNAs 34a, 122, and 192 are linked to obesity-associated inflammation and metabolic disease in pediatric patients. Int. J. Obes. 45:81763–72
     [Google Scholar]
163. 163.

     Ortega FJ, Mercader JM, Catalán V, Moreno-Navarrete JM, Pueyo N et al. 2013. Targeting the circulating microRNA signature of obesity. Clin. Chem. 59:5781–92
     [Google Scholar]
164. 164.

     Nair S, Guanzon D, Jayabalan N, Lai A, Scholz-Romero K et al. 2021. Extracellular vesicle-associated miRNAs are an adaptive response to gestational diabetes mellitus. J. Transl. Med. 19:360
     [Google Scholar]
165. 165.

     Prattichizzo F, Matacchione G, Giuliani A, Sabbatinelli J, Olivieri F et al. 2021. Extracellular vesicle-shuttled miRNAs: a critical appraisal of their potential as nano-diagnostics and nano-therapeutics in type 2 diabetes mellitus and its cardiovascular complications. Theranostics 11:31031–45
     [Google Scholar]
166. 166.

     Frühbeis C, Helmig S, Tug S, Simon P, Krämer-Albers E-M. 2015. Physical exercise induces rapid release of small extracellular vesicles into the circulation. J. Extracell. Vesicles 4:28239
     [Google Scholar]
167. 167.

     Brahmer A, Neuberger E, Esch-Heisser L, Haller N, Jorgensen MM et al. 2019. Platelets, endothelial cells and leukocytes contribute to the exercise-triggered release of extracellular vesicles into the circulation. J. Extracell. Vesicles 8:11615820
     [Google Scholar]
168. 168.

     Whitham M, Parker BL, Friedrichsen M, Hingst JR, Hjorth M et al. 2018. Extracellular vesicles provide a means for tissue crosstalk during exercise. Cell Metab. 27:1237–51
     [Google Scholar]
169. 169.

     Hubal MJ, Nadler EP, Ferrante SC, Barberio MD, Suh J-H et al. 2017. Circulating adipocyte-derived exosomal microRNAs associated with decreased insulin resistance after gastric bypass. Obesity 25:1102–10
     [Google Scholar]
170. 170.

     Witczak JK, Min T, Prior SL, Stephens JW, James PE, Rees A. 2017. Bariatric surgery is accompanied by changes in extracellular vesicle-associated and plasma fatty acid binding protein 4. Obes. Surg. 28:3767–74
     [Google Scholar]
171. 171.

     Ghai V, Kim T-K, Etheridge A, Nielsen T, Hansen T et al. 2019. Extracellular vesicle encapsulated microRNAs in patients with type 2 diabetes are affected by metformin treatment. J. Clin. Med. 8:5617
     [Google Scholar]
172. 172.

     Nunez Lopez YO, Pratley RE 2018. Pioglitazone alters the cargo composition of circulating exosomes in subjects with type 2 diabetes. Diabetes 67:Suppl. 11120–P
     [Google Scholar]