Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/5390
MiR-93 Controls Adiposity via Inhibition of Sirt7 and Tbx3
Cioffi, Michele | Vallespinos-Serrano, Mireia | Trabulo, Sara M. | Jose Fernandez-Marcos, Pablo | Firment, Ashley N. | Vazquez, Berta N. | Vieira, Catarina R. | Mulero, Francisca CNIO | Camara, Juan A. | Cronin, Ultan P. | Perez, Manuel | Soriano, Joaquim | Galvez, Beatriz G. CNIC | Castells-Garcia, Alvaro | Haage, Verena | Raj, Deepak | Megias Vazquez, Diego CNIO | Hahn, Stephan | Serrano, Lourdes | Moon, Anne | Aicher, Alexandra | Heeschen, Christopher CNIO
Cell Rep. 2015; 12(10):1594-605
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.
ADIPOCYTE DIFFERENTIATION | STEM-CELLS | INSULIN-RESISTANCE | IN-VIVO | TISSUE | IDENTIFICATION | REGULATOR | OBESITY | GROWTH | RISK