Cioffi, MicheleVallespinos-Serrano, MireiaTrabulo, Sara M.Jose Fernandez-Marcos, PabloFirment, Ashley N.Vazquez, Berta N.Vieira, Catarina R.Mulero, FranciscaCamara, Juan A.Cronin, Ultan P.Perez, ManuelSoriano, JoaquimGalvez, Beatriz G.Castells-Garcia, AlvaroHaage, VerenaRaj, DeepakMegias Vazquez, DiegoHahn, StephanSerrano, LourdesMoon, AnneAicher, AlexandraHeeschen, Christopher2017-11-272017-11-272015Cell Rep. 2015; 12(10):1594-6052211-1247http://hdl.handle.net/20.500.12105/5390Conquering obesity has become a major socioeconomic challenge. Here, we show that reduced expression of the miR-25-93-106b cluster, or miR-93 alone, increases fat mass and, subsequently, insulin resistance. Mechanistically, we discovered an intricate interplay between enhanced adipocyte precursor turnover and increased adipogenesis. First, miR-93 controls Tbx3, thereby limiting self-renewal in early adipocyte precursors. Second, miR-93 inhibits the metabolic target Sirt7, which we identified as a major driver of in vivo adipogenesis via induction of differentiation and maturation of early adipocyte precursors. Using mouse parabiosis, obesity in mir-25-93-106b(-/-) mice could be rescued by restoring levels of circulating miRNA and subsequent inhibition of Tbx3 and Sirt7. Downregulation of miR-93 also occurred in obese ob/ob mice, and this phenocopy of mir-25-93-106b(-/-) was partially reversible with injection of miR-93 mimics. Our data establish miR-93 as a negative regulator of adipogenesis and a potential therapeutic option for obesity and the metabolic syndrome.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/ADIPOCYTE DIFFERENTIATIONSTEM-CELLSINSULIN-RESISTANCEIN-VIVOTISSUEIDENTIFICATIONREGULATOROBESITYGROWTHRISKAttribution-NonCommercial-NoDerivatives 4.0 Internacional26321631121594-160510.1016/j.celrep.2015.08.006Cell Reportsopen access