Adipose-derived circulating miRNAs regulate gene expression in other tissues

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, Phillip Gorden and C. Ronald Kahn ()
Additional contact information
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
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
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

Nature, 2017, vol. 542, issue 7642, 450-455

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature21365

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