MiR-93 Controls Adiposity via Inhibition of Sirt7 and Tbx3

Michele Cioffi, Mireia Vallespinos-Serrano, Sara M. Trabulo, Pablo Jose Fernandez-Marcos, Ashley N. Firment, Berta N. Vazquez, Catarina R. Vieira, Francesca Mulero, Juan A. Camara, Ultan P. Cronin, Manuel Perez, Joaquim Soriano, Beatriz G. Galvez, Alvaro Castells-Garcia, Verena Haage, Deepak Raj, Diego Megias, Stephan Hahn, Lourdes Serrano, Anne MoonAlexandra Aicher, Christopher Heeschen

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

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. Cioffi et al. provide evidence that miRNA-93 suppresses Tbx3 and Sirt7, thereby controlling expansion of adipocyte precursors and inhibiting adipogenesis, respectively.

Original languageEnglish (US)
Pages (from-to)1594-1605
Number of pages12
JournalCell Reports
Volume12
Issue number10
DOIs
StatePublished - Sep 8 2015

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology

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