MiR-93 Controls Adiposity via Inhibition of Sirt7 and Tbx3
2015; Cell Press; Volume: 12; Issue: 10 Linguagem: Inglês
10.1016/j.celrep.2015.08.006
ISSN2639-1856
AutoresMichele Cioffi, Mireia Vallespinos-Serrano, Sara Trabulo, Pablo J. Fernández-Marcos, Ashley Firment, Berta N. Vázquez, Catarina R. Vieira, Francisca Mulero, Juan A. Cámara, Ultan P. Cronin, Manuel Pérez‐Martínez, Joaquím Soriano, Beatriz G. Gálvez, Álvaro Castells-García, Verena Haage, Deepak B. Thimiri Govinda Raj, Diego Megı́as, Stephan A. Hahn, Lourdes Serrano, Anne Moon, Alexandra Aicher, Christopher Heeschen,
Tópico(s)Cancer-related molecular mechanisms research
ResumoConquering 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.
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