title: Mir193b-365 is essential for brown fat differentiation.
abstract: Mammals have two principal types of fat. White adipose tissue primarily serves to store extra energy as triglycerides, whereas brown adipose tissue is specialized to burn lipids for heat generation and energy expenditure as a defence against cold and obesity. Recent studies have demonstrated that brown adipocytes arise in vivo from a Myf5-positive, myoblastic progenitor by the action of Prdm16 (PR domain containing 16). Here, we identified a brown-fat-enriched miRNA cluster, MiR-193b-365, as a key regulator of brown fat development. Blocking miR-193b and/or miR-365 in primary brown preadipocytes markedly impaired brown adipocyte adipogenesis by enhancing Runx1t1 (runt-related transcription factor 1; translocated to, 1) expression, whereas myogenic markers were significantly induced. Forced expression of Mir193b and/or Mir365 in C2C12 myoblasts blocked the entire programme of myogenesis, and, in adipogenic conditions, miR-193b induced myoblasts to differentiate into brown adipocytes. Mir193b-365 was upregulated by Prdm16 partially through Pparα. Our results demonstrate that Mir193b-365 serves as an essential regulator for brown fat differentiation, in part by repressing myogenesis.
authors: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors: Lei
authors: L
authors: Sun
authors: Huangming
authors: H
authors: Xie
authors: Marcelo A
authors: MA
authors: Mori
authors: Ryan
authors: R
authors: Alexander
authors: Bingbing
authors: B
authors: Yuan
authors: Shilpa M
authors: SM
authors: Hattangadi
authors: Qingqing
authors: Q
authors: Liu
authors: C Ronald
authors: CR
authors: Kahn
authors: Harvey F
authors: HF
authors: Lodish
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D002001:Adipose Tissue, Brown / Q000254:growth & development* / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics; D014162:Transfection
chemical_list: C000589043:MIRN365 microRNA, mouse; D035683:MicroRNAs; D009841:Oligonucleotides; C477371:locked nucleic acid