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Nature. 2017 Feb 23;542(7642):450-455. doi: 10.1038/nature21365. Epub 2017 Feb 15.

Adipose-derived circulating miRNAs regulate gene expression in other tissues.

Author information

1
Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
2
Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Brazil.
3
Bioinformatics Core, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
4
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
5
ETHZ, Department of Health Sciences and Metabolism, Zurich, Switzerland.
6
Department of Biomedicine, Experimental Hematology, University Hospital Basel, Switzerland.
7
MGH Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
8
Diabetes, Endocrinology and Obesity Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, USA.

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.

PMID:
28199304
PMCID:
PMC5330251
DOI:
10.1038/nature21365
[Indexed for MEDLINE]
Free PMC Article

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