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.
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Zhao et al. engineered exosomes using ADSC to treat obesity; smart exosomes reduced WAT inflammation, improved energy expenditure and resilience to obesity progression.
“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]
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- 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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › 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
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