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

  • Thomou T Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
  • Mori MA Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Brazil.
  • Dreyfuss JM Bioinformatics Core, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
  • Konishi M Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
  • Sakaguchi M Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
  • Wolfrum C ETHZ, Department of Health Sciences and Metabolism, Zurich, Switzerland.
  • Rao TN Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
  • Winnay JN Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
  • Garcia-Martin R Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
  • Grinspoon SK MGH Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • Gorden P Diabetes, Endocrinology and Obesity Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, USA.
  • Kahn CR Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
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  • 2017-02-16
Published in:
  • Nature. - 2017
3' Untranslated Regions
Adipokines
Adipose Tissue
Adipose Tissue, Brown
Adipose Tissue, White
Animals
Exosomes
Fibroblast Growth Factors
Gene Expression Regulation
Genes, Reporter
Glucose Tolerance Test
Liver
Male
Mice
MicroRNAs
Models, Biological
Organ Specificity
Paracrine Communication
RNA, Messenger
Ribonuclease III
Transcription, Genetic
English 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/199741
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