title: Adipose-derived circulating miRNAs regulate gene expression in other tissues.
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.
authors.affiliation: Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thomou
authors.affiliation: Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Brazil.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Mori
authors.affiliation: Bioinformatics Core, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.|Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Dreyfuss
authors.affiliation: Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Konishi
authors.affiliation: Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Masaji
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: ETHZ, Department of Health Sciences and Metabolism, Zurich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Wolfrum
authors.affiliation: Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.|Department of Biomedicine, Experimental Hematology, University Hospital Basel, Switzerland.
authors.forename: Tata Nageswara
authors.initials: TN
authors.lastname: Rao
authors.affiliation: Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jonathon N
authors.initials: JN
authors.lastname: Winnay
authors.affiliation: Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Garcia-Martin
authors.affiliation: MGH Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Grinspoon
authors.affiliation: Diabetes, Endocrinology and Obesity Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Gorden
authors.affiliation: Section on Integrative Physiology &Metabolism, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism* / Q000637:transplantation; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D052436:Adipose Tissue, White / Q000378:metabolism / Q000637:transplantation; D000818:Animals; D055354:Exosomes / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D005951:Glucose Tolerance Test; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009928:Organ Specificity / Q000235:genetics; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000235:genetics; D043244:Ribonuclease III / Q000172:deficiency / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D054392:Adipokines; D035683:MicroRNAs; C573158:Mirn99 microRNA, mouse; D012333:RNA, Messenger; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D043244:Ribonuclease III