The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Exosomes From Adipose-Derived Stem Cells Attenuate Adipose Inflammation and Obesity Through Polarizing M2 Macrophages and Beiging in White Adipose Tissue
Abstract
Adipose-derived stem cells (ADSCs) play critical roles in controlling obesity-associated inflammation and metabolic disorders. Exosomes from ADSCs exert protective effects in several diseases, but their roles in obesity and related pathological conditions remain unclear. In this study, we showed that treatment of obese mice with ADSC-derived exosomes facilitated their metabolic homeostasis, including improved insulin sensitivity (27.8% improvement), reduced obesity, and alleviated hepatic steatosis. ADSC-derived exosomes drove alternatively activated M2 macrophage polarization, inflammation reduction, and beiging in white adipose tissue (WAT) of diet-induced obese mice. Mechanistically, exosomes from ADSCs transferred into macrophages to induce anti-inflammatory M2 phenotypes through the transactivation of arginase-1 by exosome-carried active STAT3. Moreover, M2 macrophages induced by ADSC-derived exosomes not only expressed high levels of tyrosine hydroxylase responsible for catecholamine release, but also promoted ADSC proliferation and lactate production, thereby favoring WAT beiging and homeostasis in response to high-fat challenge. These findings delineate a novel exosome-mediated mechanism for ADSC–macrophage cross talk that facilitates immune and metabolic homeostasis in WAT, thus providing potential therapy for obesity and diabetes.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The smart exosomes reduced WAT inflammation, improved energy expenditure and resilience to obesity progression [136].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [136]
Citations
Cites
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles
Colombo, M., Raposo, G., & Théry, C. (2014) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-101512-122326 · Cited by 6,186
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664
Extracellular vesicles: biology and emerging therapeutic opportunities
EL Andaloussi, S., Mäger, I., Breakefield, X. O., & Wood, M. J. A. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3978 · Cited by 3,571
Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human
Wu, J., Boström, P., Sparks, L. M., Li, Y., Choi, J. H., Giang, A.-H., Khandekar, M. J., Virtanen, K. A., Nuutila, P., Schaart, G., et al. (2012) · Cell · doi:10.1016/j.cell.2012.05.016 · Cited by 3,406
Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury
Lai, R. C., Arslan, F., Lee, M. M., Sze, N. S. K., Choo, A., Chen, T. S., Salto-Tellez, M., Timmers, L., Lee, C. N., El Oakley, R. M., et al. (2010) · Stem Cell Research · doi:10.1016/j.scr.2009.12.003 · Cited by 2,215
Obesity and Diabetes in the Developing World — A Growing Challenge
Hossain, P., Kawar, B., & El Nahas, M. (2007) · New England Journal of Medicine · doi:10.1056/nejmp068177 · Cited by 2,200
Adipose tissue remodeling and obesity
Sun, K., Kusminski, C. M., & Scherer, P. E. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45887 · Cited by 1,941
Concise review: MSC-derived exosomes for cell-free therapy
Phinney, D. G., & Pittenger, M. F. (2017) · Stem Cells · doi:10.1002/stem.2575 · Cited by 1,834
Eosinophils Sustain Adipose Alternatively Activated Macrophages Associated with Glucose Homeostasis
Wu, D., Molofsky, A. B., Liang, H.-E., Ricardo-González, R. R., Jouihan, H. A., Bando, J. K., Chawla, A., & Locksley, R. M. (2011) · Science · doi:10.1126/science.1201475 · Cited by 1,411
Macrophage-mediated inflammation in metabolic disease
Chawla, A., Nguyen, K. D., & Goh, Y. P. S. (2011) · Nature reviews. Immunology · doi:10.1038/nri3071 · Cited by 1,314
Scherer, P. E. (2006) · Diabetes · doi:10.2337/db06-0263 · Cited by 1,092
Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis
Nguyen, K. D., Qiu, Y., Cui, X., Goh, Y. P. S., Mwangi, J., David, T., Mukundan, L., Brombacher, F., Locksley, R. M., & Chawla, A. (2011) · Nature · doi:10.1038/nature10653 · Cited by 1,038
Qiu, Y., Nguyen, K. D., Odegaard, J. I., Cui, X., Tian, X., Locksley, R. M., Palmiter, R. D., & Chawla, A. (2014) · Cell · doi:10.1016/j.cell.2014.03.066 · Cited by 888
Exosome Transfer from Stromal to Breast Cancer Cells Regulates Therapy Resistance Pathways
Boelens, M. C., Wu, T. J., Nabet, B. Y., Xu, B., Qiu, Y., Yoon, T., Azzam, D. J., Victor, C. T.-S., Wiemann, B. Z., Ishwaran, H., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.051 · Cited by 819
Mesenchymal stem cell: An efficient mass producer of exosomes for drug delivery
Yeo, R. W. Y., Lai, R. C., Zhang, B., Tan, S. S., Yin, Y., Teh, B. J., & Lim, S. K. (2013) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.07.001 · Cited by 746
Regulatory Mechanisms for Adipose Tissue M1 and M2 Macrophages in Diet-Induced Obese Mice
Fujisaka, S., Usui, I., Bukhari, A., Ikutani, M., Oya, T., Kanatani, Y., Tsuneyama, K., Nagai, Y., Takatsu, K., Urakaze, M., et al. (2009) · Diabetes · doi:10.2337/db08-1475 · Cited by 731
Functions of Polyamines in Mammals
Pegg, A. E. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.r116.731661 · Cited by 720
Mesenchymal Stem Cells Secrete Immunologically Active Exosomes
Zhang, B., Yin, Y., Lai, R. C., Tan, S. S., Choo, A. B. H., & Lim, S. K. (2013) · Stem Cells and Development · doi:10.1089/scd.2013.0479 · Cited by 710
Wu, H., Ghosh, S., Perrard, X. D., Feng, L., García, G., Perrard, J. L., Sweeney, J. F., Peterson, L. E., Chan, L., Smith, C. W., et al. (2007) · Circulation · doi:10.1161/circulationaha.106.638379 · Cited by 696
Targeting adipose tissue in the treatment of obesity-associated diabetes
Kusminski, C. M., Bickel, P. E., & Scherer, P. E. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.75 · Cited by 678
Concise Review: Adipose‐Derived Stem Cells as a Novel Tool for Future Regenerative Medicine
Mizuno, H., Tobita, M., & Uysal, Ç. A. (2012) · Stem Cells · doi:10.1002/stem.1076 · Cited by 668
UCP1 in Brite/Beige Adipose Tissue Mitochondria Is Functionally Thermogenic
Shabalina, I. G., Petrovič, N., de Jong, J. M. A., Kalinovich, A., Cannon, B., & Nedergaard, J. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.10.044 · Cited by 659
Munder, M., Eichmann, K., & Modolell, M. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.11.5347 · Cited by 647
González, M. A., González‐Rey, E., Rico, L., Büscher, D., & Delgado, M. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.11.041 · Cited by 631
Plasma exosome microRNAs are indicative of breast cancer
Hannafon, B. N., Trigoso, Y. D., Calloway, C. L., Zhao, Y. D., Lum, D. H., Welm, A. L., Zhao, Z. J., Blick, K. E., Dooley, W. C., & Ding, W. (2016) · Breast Cancer Research · doi:10.1186/s13058-016-0753-x · Cited by 603
Adipose Tissue Exosome-Like Vesicles Mediate Activation of Macrophage-Induced Insulin Resistance
Deng, Z., Poliakov, A., Hardy, R. W., Clements, R. H., Liu, C., Liu, Y., Wang, J., Xiang, X., Zhang, S., Zhuang, X., et al. (2009) · Diabetes · doi:10.2337/db09-0216 · Cited by 596
Self-citationMesenchymal stem cell exosomes
Lai, R. C., Yeo, R. W. Y., & Lim, S. K. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.03.001 · Cited by 589
STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients
Vasquez-Dunddel, D., Pan, F., Zeng, Q., Gorbounov, M., Albesiano, E., Fu, J. L., Blosser, R. L., Tam, A. J., Bruno, T. C., Zhang, H., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci60083 · Cited by 522
Self-citationGonzalez, M. A., González‐Rey, E., Rico, L., Büscher, D., & Delgado, M. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24405 · Cited by 489
Szántó, A., Bálint, B. L., Nagy, Z. S., Barta, E., Dezsö, B., Pap, A., Széles, L., Póliska, S., Oros, M., Evans, R. M., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.11.009 · Cited by 462
Stromal cells and stem cells in clinical bone regeneration
Grayson, W. L., Bunnell, B. A., Martin, E. C., Frazier, T. P., Hung, B. P., & Gimble, J. M. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.234 · Cited by 429
Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation
Monticelli, L. A., Buck, M. D., Flamar, A.-L., Saenz, S. A., Wojno, E. D. T., Yudanin, N. A., Osborne, L. C., Hepworth, M. R., Tran, S. V., Rodewald, H.-R., et al. (2016) · Nature Immunology · doi:10.1038/ni.3421 · Cited by 299
Carrière, A., Jeanson, Y., Berger-Müller, S., André, M., Chenouard, V., Arnaud, E., Barreau, C., Walther, R., Galinier, A., Wdziekonski, B., et al. (2014) · Diabetes · doi:10.2337/db13-1885 · Cited by 277
Regulation of chronic inflammatory and immune processes by extracellular vesicles
Robbins, P. D., Dorronsoro, A., & Booker, C. N. (2016) · Journal of Clinical Investigation · doi:10.1172/jci81131 · Cited by 266
Brown and beige fat: Molecular parts of a thermogenic machine
Cohen, P., & Spiegelman, B. M. (2015) · Diabetes · doi:10.2337/db15-0318 · Cited by 259
Exosomes as nano-theranostic delivery platforms for gene therapy
Tan, A., Rajadas, J., & Seifalian, A. M. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.06.014 · Cited by 246
Lin, K., Yip, H., Shao, P., Wu, S., Chen, K., Chen, Y.-T., Yang, C., Sun, C., Kao, G., Chen, S., et al. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.04.061 · Cited by 241
Diabetes impairs adipose tissue–derived stem cell function and efficiency in promoting wound healing
Cianfarani, F., Toietta, G., Rocco, G. D., Cesareo, E., Zambruno, G., & Odorisio, T. (2013) · Wound Repair and Regeneration · doi:10.1111/wrr.12051 · Cited by 231
Macrophage polarization in metabolic disorders
Chinetti, G., & Staels, B. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32834a77b4 · Cited by 193
Singh, P., Smith, V. L., Karakousis, P. C., & Schorey, J. S. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1103638 · Cited by 191
Bassi, Ê. J., Moraes‐Vieira, P. M., Moreira-Sá, C. S. R., de Almeida, D. C., Vieira, L. M., Cunha, C. D. S., Hiyane, M. I., Basso, A. S., Pacheco‐Silva, Á., & Câmara, N. O. S. (2012) · Diabetes · doi:10.2337/db11-0844 · Cited by 161
Mesenchymal Stem Cell Exosome Ameliorates Reperfusion Injury Through Proteomic Complementation
Lai, R. C., Yeo, R. W. Y., Tan, K. H., & Lim, S. K. (2013) · Regenerative Medicine · doi:10.2217/rme.13.4 · Cited by 132
Exosomes Released by Islet-Derived Mesenchymal Stem Cells Trigger Autoimmune Responses in NOD Mice
Rahman, M. J., Regn, D., Bashratyan, R., & Dai, Y. D. (2013) · Diabetes · doi:10.2337/db13-0859 · Cited by 122
Strong, A. L., Bowles, A. C., Wise, R. M., Morand, J. P., Dutreil, M. F., Gimble, J. M., & Bunnell, B. A. (2015) · Stem Cells · doi:10.1002/stem.2272 · Cited by 96
Shang, Q., Bai, Y., Wang, G., Song, Q., Guo, C. H., Zhang, L., & Wang, Q. (2015) · Stem Cells and Development · doi:10.1089/scd.2014.0557 · Cited by 84
Self-citationVentura, S., Aryee, D. N. T., Felicetti, F., Feo, A. D., Mancarella, C., Manara, M. C., Picci, P., Colombo, M. P., Kovar, H., Carè, A., et al. (2015) · Oncogene · doi:10.1038/onc.2015.463 · Cited by 72
Adipose-Derived Mesenchymal Stem Cells Ameliorate Lipid Metabolic Disturbance in Mice
Liu, G.-Y., Liu, J., Wang, Y., Liu, Y., Shao, Y., Han, Y., Qin, Y.-R., Xiao, F., Li, P., Zhao, L., et al. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0239 · Cited by 52
Flagged first, then by citations
Cited by
Sorted by citations
Extracellular vesicles as tools and targets in therapy for diseases
Kumar, M. A., Baba, S. K., Sadida, H. Q., Al-Marzooqi, S. K., Jerobin, J., Altemani, F. H., Algehainy, N. A., Alanazi, M. A., Abou‐Samra, A., Kumar, R., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01735-1 · Cited by 1,545
Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease
Mori, M. A., Ludwig, R. G., García-Martín, R., Brandão, B. B., & Kahn, C. R. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.07.011 · Cited by 990
Han, Y., Yang, J., Fang, J., Zhou, Y., Candi, E., Wang, J., Hua, D., Shao, C., & Shi, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00932-0 · Cited by 720
Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome
Kahn, C. R., Wang, G., & Lee, K. Y. (2019) · Journal of Clinical Investigation · doi:10.1172/jci129187 · Cited by 686
Ha, D. H., Kim, H.-K., Lee, J., Kwon, H. H., Park, G., Yang, S. H., Jung, J. Y., Choi, H., Lee, J. H., Sung, S., et al. (2020) · Cells · doi:10.3390/cells9051157 · Cited by 556
Metadata
- Authors
- Zhao, H., Shang, Q., Pan, Z., Bai, Y., Li, Z., Zhang, H., Zhang, Q., Guo, C., Zhang, L., & Wang, Q.
- Affiliations
- Shandong University (CN)
- Corresponding author
- Wang, Qun
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2017-11-13
- Volume
- 67
- Issue
- 2
- Pages
- 235-247
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2769957434
- Cited by
- 657
- References
- 50
- Citations by year
- 2026: 53 · 2025: 74 · 2024: 98 · 2023: 83 · 2022: 108 · 2021: 94 · 2020: 77 · 2019: 50 · 2018: 19
- FWCI
- 16.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81770838, 81471065, 81270923)
- Shandong Major Research Program (2016GSF201005)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- adipose-derived stem cells, exosomes, obesity, adipose tissue inflammation, M2 macrophage polarization, insulin sensitivity, hepatic steatosis, arginase-1, STAT3, tyrosine hydroxylase, catecholamine release, metabolic homeostasis
- MeSH terms
- Adipocytes, Beige, Animals, Cell Communication, Cells, Cultured, Insulin Resistance, Macrophage Activation, Male, Mice, Inbred C57BL, Microscopy, Fluorescence, Obesity, Phagocytosis, Biomarkers, Cell Polarity, Macrophages, Peritoneal, Microscopy, Electron, Transmission, Cell Proliferation, Adipogenesis, Adipocytes, White, Adult Stem Cells, Exosomes, Diet, High-Fat, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review