MiR-93 Controls Adiposity via Inhibition of Sirt7 and Tbx3

被引：131

作者：

Cioffi, Michele ^{[1
]}

Vallespinos-Serrano, Mireia ^{[1
]}

Trabulo, Sara M. ^{[1
,10
]}

Jose Fernandez-Marcos, Pablo ^{[2
]}

Firment, Ashley N. ^{[7
]}

Vazquez, Berta N. ^{[8
]}

Vieira, Catarina R. ^{[1
]}

Mulero, Francesca ^{[3
]}

Camara, Juan A. ^{[3
]}

Cronin, Ultan P. ^{[4
]}

Perez, Manuel ^{[5
]}

Soriano, Joaquim ^{[5
]}

Galvez, Beatriz G. ^{[6
]}

Castells-Garcia, Alvaro ^{[1
]}

Haage, Verena ^{[1
]}

Raj, Deepak ^{[10
]}

Megias, Diego ^{[5
]}

Hahn, Stephan ^{[9
]}

Serrano, Lourdes ^{[8
]}

Moon, Anne ^{[7
]}

Aicher, Alexandra ^{[1
,10
]}

Heeschen, Christopher ^{[1
,10
]}

机构：

[1] Spanish Natl Canc Res Ctr CNIO, Stem Cells & Canc Grp, Madrid 28028, Spain

[2] Spanish Natl Canc Res Ctr CNIO, Tumor Suppress Grp, Madrid 28028, Spain

[3] Spanish Natl Canc Res Ctr CNIO, Bioimaging, Madrid 28028, Spain

[4] Spanish Natl Canc Res Ctr CNIO, Flow Cytometry Unit, Madrid 28028, Spain

[5] Spanish Natl Canc Res Ctr CNIO, Confocal Microscopy Unit, Madrid 28028, Spain

[6] Spanish Natl Cardiovasc Res Ctr CNIC, Madrid 28028, Spain

[7] Weis Ctr Res, Danville, PA 17822 USA

[8] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA

[9] Ruhr Univ Bochum, Dept Mol Gastrointestinal Oncol, D-44801 Bochum, Germany

[10] Queen Mary Univ London, Barts Canc Inst, Stem Cells Canc & Ageing, London EC1M 6BQ, England

来源：

CELL REPORTS | 2015年 / 12卷 / 10期

基金：

欧洲研究理事会;

关键词：

ADIPOCYTE DIFFERENTIATION; TISSUE; IDENTIFICATION; CELLS; REGULATOR; OBESITY; GROWTH;

D O I：

10.1016/j.celrep.2015.08.006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：1594 / 1605

页数：12

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