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00925njm 22002777a 4500 dc Cioffi, Michele author Vallespinos-Serrano, Mireia author Trabulo, Sara M. author Jose Fernandez-Marcos, Pablo author Firment, Ashley N. author Vazquez, Berta N. author Vieira, Catarina R. author Mulero, Francisca author Camara, Juan A. author Cronin, Ultan P. author Perez, Manuel author Soriano, Joaquim author Galvez, Beatriz G. author Castells-Garcia, Alvaro author Haage, Verena author Raj, Deepak author Megias Vazquez, Diego author Hahn, Stephan author Serrano, Lourdes author Moon, Anne author Aicher, Alexandra author Heeschen, Christopher author 2015 Conquering 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. Cell Rep. 2015; 12(10):1594-605 10.1016/j.celrep.2015.08.006 2211-1247 Cell Reports 26321631 http://hdl.handle.net/20.500.12105/5390 ADIPOCYTE DIFFERENTIATION STEM-CELLS INSULIN-RESISTANCE IN-VIVO TISSUE IDENTIFICATION REGULATOR OBESITY GROWTH RISK MiR-93 Controls Adiposity via Inhibition of Sirt7 and Tbx3