Adipose tissue macrophage-derived exosomal miRNAs can modulate in vivo and in vitro insulin sensitivity
Open accessAbstract
MiRNAs are regulatory molecules that can be packaged into exosomes and secreted from cells. Here, we show that adipose tissue macrophages (ATMs) in obese mice secrete miRNA-containing exosomes (Exos), which cause glucose intolerance and insulin resistance when administered to lean mice. Conversely, ATM Exos obtained from lean mice improve glucose tolerance and insulin sensitivity when administered to obese recipients. miR-155 is one of the miRNAs overexpressed in obese ATM Exos, and earlier studies have shown that PPARγ is a miR-155 target. Our results show that miR-155KO animals are insulin sensitive and glucose tolerant compared to controls. Furthermore, transplantation of WT bone marrow into miR-155KO mice mitigated this phenotype. Taken together, these studies show that ATMs secrete exosomes containing miRNA cargo. These miRNAs can be transferred to insulin target cell types through mechanisms of paracrine or endocrine regulation with robust effects on cellular insulin action, in vivo insulin sensitivity, and overall glucose homeostasis.
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Injections of adipose tissue macrophage-derived EVs isolated from lean mice improve glucose tolerance and insulin-sensitivity of diet-induced obese mice.
“injections of adipose tissue macrophage-derived EVs isolated from lean mice improved glucose tolerance and insulin-sensitivity of diet-induced obese mice”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Ying et al., 2017
MicroRNAs located in exosomes of adipocytes and macrophages of adipose tissue and secreted into circulation can influence the development of insulin resistance through mechanisms such as inhibition of PPAR-gamma expression and affecting PI3K/AKT-GLUT4 signaling pathway.
“Studies show that these particles, located in exosomes of adipocytes and macrophages of adipose tissue and secreted from them into the circulation, can influence the development of IR through mechanisms, such as inhibition of peroxisome proliferator-activated receptor (PPAR-gamma) expression and affecting PI3K/AKT-GLUT4 signaling pathway [57,58,59].”
From The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome (2022) · cites this paper as [57]
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- Authors
- Ying, W., Riopel, M., Bandyopadhyay, G., Dong, Y., Birmingham, A., Seo, J. B., Ofrecio, J. M., Wollam, J., Hernandez-Carretero, A., Fu, W., Li, P., & Olefsky, J. M.
- Affiliations
- University of California San Diego (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- UC San Diego Health System (US)
- Corresponding author
- Olefsky, Jerrold M.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 171
- Issue
- 2
- Pages
- 372-384.e12
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2758187157
- Cited by
- 1,191
- References
- 65
- Citations by year
- 2026: 79 · 2025: 126 · 2024: 148 · 2023: 137 · 2022: 161 · 2021: 194 · 2020: 142 · 2019: 114 · 2018: 80 · 2017: 6 · 2013: 1
- FWCI
- 38.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association (16POST31350039)
- National Natural Science Foundation of China (81600610)
- UCSD/UCLA Diabetes Research Center Pilot and Feasibility (P30 DK063491)
- UC San Diego Clinical and Translational Research Institute (UL1TR001442)
- U.S. National Institute of Diabetes and Digestive and Kidney Diseases (DK033651, DK074868, DK063491, DK09062)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- adipose tissue macrophages, exosomes, microRNA, miR-155, insulin resistance, insulin sensitivity, glucose tolerance, obesity, PPARγ, bone marrow transplantation, paracrine signaling, hormonal regulation, glucose homeostasis
- MeSH terms
- Adipose Tissue, Animals, Cells, Cultured, Glucose, Insulin Resistance, Liver, Macrophages, Male, Mice, Inbred C57BL, Signal Transduction, Adipocytes, Muscle, Skeletal, Hepatocytes, Muscle Cells, MicroRNAs, Mice
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