Cited by 671Extracellular vesicles in diseaseAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

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Exosomes From Adipose-Derived Stem Cells Attenuate Adipose Inflammation and Obesity Through Polarizing M2 Macrophages and Beiging in White Adipose Tissue

Zhao, Hui, Shang, Qianwen, Pan, Zhenzhen, Bai, Yang, Li, Zequn, Zhang, Huiying, Zhang, Qiu, Guo, Chun, Zhang, Lining, Wang, Qun·2018·Diabetes

DOI 10.2337/db17-0356

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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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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: Zhao, Hui
Pan, Zhenzhen
Bai, Yang
Li, Zequn
Zhang, Huiying
Zhang, Qiu
Guo, Chun
Zhang, Lining
Wang, Qun
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2017-11-13
Volume: 67
Issue: 2
Pages: 235-247
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/db17-0356
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
Licence: www.diabetesjournals.org/content/license (vor, 70 d)
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

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Exosomes From Adipose-Derived Stem Cells Attenuate Adipose Inflammation and Obesity Through Polarizing M2 Macrophages and Beiging in White Adipose Tissue

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