Author
Listed:
- Thomas Thomou
(Section on Integrative Physiology & Metabolism, Joslin Diabetes Center and Harvard Medical School)
- Marcelo A. Mori
(University of Campinas)
- Jonathan M. Dreyfuss
(Bioinformatics Core, Joslin Diabetes Center and Harvard Medical School
Boston University)
- Masahiro Konishi
(Section on Integrative Physiology & Metabolism, Joslin Diabetes Center and Harvard Medical School)
- Masaji Sakaguchi
(Section on Integrative Physiology & Metabolism, Joslin Diabetes Center and Harvard Medical School)
- Christian Wolfrum
(ETHZ)
- Tata Nageswara Rao
(Section on Integrative Physiology & Metabolism, Joslin Diabetes Center and Harvard Medical School
Experimental Hematology, University Hospital Basel)
- Jonathon N. Winnay
(Section on Integrative Physiology & Metabolism, Joslin Diabetes Center and Harvard Medical School)
- Ruben Garcia-Martin
(Section on Integrative Physiology & Metabolism, Joslin Diabetes Center and Harvard Medical School)
- Steven K. Grinspoon
(MGH Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School)
- Phillip Gorden
(Diabetes, Endocrinology and Obesity Branch, NIDDK, National Institutes of Health)
- C. Ronald Kahn
(Section on Integrative Physiology & Metabolism, Joslin Diabetes Center and Harvard Medical School)
Abstract
Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue—brown especially—into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21. This gene regulation can be mimicked by the administration of normal, but not ADicerKO, serum exosomes. Expression of a human-specific miRNA in the brown adipose tissue of one mouse in vivo can also regulate its 3′ UTR reporter in the liver of another mouse through serum exosomal transfer. Thus, adipose tissue constitutes an important source of circulating exosomal miRNAs, which can regulate gene expression in distant tissues and thereby serve as a previously undescribed form of adipokine.
Suggested Citation
Thomas Thomou & Marcelo A. Mori & Jonathan M. Dreyfuss & Masahiro Konishi & Masaji Sakaguchi & Christian Wolfrum & Tata Nageswara Rao & Jonathon N. Winnay & Ruben Garcia-Martin & Steven K. Grinspoon &, 2017.
"Adipose-derived circulating miRNAs regulate gene expression in other tissues,"
Nature, Nature, vol. 542(7642), pages 450-455, February.
Handle:
RePEc:nat:nature:v:542:y:2017:i:7642:d:10.1038_nature21365
DOI: 10.1038/nature21365
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Cited by:
- Jinhong Xu & Le Cui & Jiaqi Wang & Shasha Zheng & Huahua Zhang & Shuo Ke & Xiaoqin Cao & Yanteng Shi & Jing Li & Ke Zen & Antonio Vidal-Puig & Chen-Yu Zhang & Liang Li & Xiaohong Jiang, 2023.
"Cold-activated brown fat-derived extracellular vesicle-miR-378a-3p stimulates hepatic gluconeogenesis in male mice,"
Nature Communications, Nature, vol. 14(1), pages 1-19, December.
- Konxhe Kulaj & Alexandra Harger & Michaela Bauer & Özüm S. Caliskan & Tilak Kumar Gupta & Dapi Menglin Chiang & Edward Milbank & Josefine Reber & Angelos Karlas & Petra Kotzbeck & David N. Sailer & Fr, 2023.
"Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo,"
Nature Communications, Nature, vol. 14(1), pages 1-13, December.
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