MiR-93 Controls Adiposity via Inhibition of Sirt7 and Tbx3
| Autor: | Cioffi, Michele, Vallespinos-Serrano, Mireia, Trabulo, Sara M., Jose Fernandez-Marcos, Pablo, Firment, Ashley N., Vazquez, Berta N., Vieira, Catarina R., Mulero, Francisca, Camara, Juan A., Cronin, Ultan P., Perez, Manuel, Soriano, Joaquim, Galvez, Beatriz G., Castells-Garcia, Alvaro, Haage, Verena, Raj, Deepak, Megias Vazquez, Diego, Hahn, Stephan, Serrano, Lourdes, Moon, Anne, Aicher, Alexandra, Heeschen, Christopher |
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| Přispěvatelé: | European Commission, Unión Europea. Comisión Europea. 7 Programa Marco, Fundación La Caixa |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Adipose tissue Mice Obese chemistry.chemical_compound Mice 0302 clinical medicine Adipocyte Adipocytes Sirtuins Cell Self Renewal lcsh:QH301-705.5 IN-VIVO Adiposity Metabolic Syndrome Mice Knockout RISK 0303 health sciences INSULIN-RESISTANCE Adipogenesis ADIPOCYTE DIFFERENTIATION Chemistry 3. Good health Adipose Tissue 030220 oncology & carcinogenesis OBESITY GROWTH Female RNA Interference REGULATOR STEM-CELLS medicine.medical_specialty Parabiosis Adipose Tissue White General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Insulin resistance Downregulation and upregulation Internal medicine 3T3-L1 Cells medicine Animals 030304 developmental biology Phenocopy IDENTIFICATION medicine.disease Mice Inbred C57BL MicroRNAs Endocrinology lcsh:Biology (General) TISSUE Metabolic syndrome Insulin Resistance T-Box Domain Proteins |
| Zdroj: | Cell Reports, Vol 12, Iss 10, Pp 1594-1605 (2015) Repisalud Instituto de Salud Carlos III (ISCIII) Cell Reports |
| ISSN: | 2211-1247 |
| Popis: | 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. We graciously thank Flor Diaz for expert technical assistance. We are grateful to Andrea Ventura for providing the mir-25-93-106b-/- mice and Elena Lopez-Guadamillas for providing visceral fad pads from ob/ob mice. Research was supported by the European Research Council Advanced Investigator Grant (Pa-CSC 233460) and the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreements 256974 (EPC-TM-NET) and 602783 (CAM-PaC). M.C. was supported by a La Caixa Fellowship. Sí |
| Databáze: | OpenAIRE |
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