title: MicroRNA-378 controls classical brown fat expansion to counteract obesity.
abstract: Both classical brown adipocytes and brown-like beige adipocytes are considered as promising therapeutic targets for obesity; however, their development, relative importance and functional coordination are not well understood. Here we show that a modest expression of miR-378/378* in adipose tissue specifically increases classical brown fat (BAT) mass, but not white fat (WAT) mass. Remarkably, BAT expansion, rather than miR-378 per se, suppresses formation of beige adipocytes in subcutaneous WAT. Despite this negative feedback, the expanded BAT depot is sufficient to prevent both genetic and high-fat diet-induced obesity. At the molecular level, we find that miR-378 targets phosphodiesterase Pde1b in BAT but not in WAT. Indeed, miR-378 and Pde1b inversely regulate brown adipogenesis in vitro in the absence of phosphodiesterase inhibitor isobutylmethylxanthine. Our work identifies miR-378 as a key regulatory component underlying classical BAT-specific expansion and obesity resistance, and adds novel insights into the physiological crosstalk between BAT and WAT.
authors.affiliation: Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Dongning
authors.initials: D
authors.lastname: Pan
authors.affiliation: Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Mao
authors.affiliation: Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Quattrochi
authors.affiliation: Program in Molecular Medicine and Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Randall H
authors.initials: RH
authors.lastname: Friedline
authors.affiliation: Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Lihua J
authors.initials: LJ
authors.lastname: Zhu
authors.affiliation: Program in Molecular Medicine and Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.affiliation: Program in Molecular Medicine and Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Lewis
authors.affiliation: Program in Gene Function and Expression and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Yong-Xu
authors.initials: YX
authors.lastname: Wang
mesh_terms: D017667:Adipocytes / Q000502:physiology; D050156:Adipogenesis / Q000235:genetics; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000502:physiology*; D052436:Adipose Tissue, White / Q000502:physiology; D000818:Animals; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000473:pathology
chemical_list: C546119:MIRN378 microRNA, mouse; D035683:MicroRNAs; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C517267:Pde1b protein, mouse