Adipose tissue mass is modulated by SLUG (SNAI2)
Autor: | Pedro A. Perez-Mancera, Inés González-Herrero, Rafael Jiménez, Camino Bermejo-Rodríguez, Isidro Sánchez-García, Teresa Flores, Michel Herranz |
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Rok vydání: | 2007 |
Předmět: |
animal structures
Slug Gene Expression Adipose tissue White adipose tissue Biology Mice chemistry.chemical_compound 3T3-L1 Cells Adipocyte Gene expression Genetics Animals Humans Molecular Biology Transcription factor Genetics (clinical) DNA Primers Mice Knockout Adipogenesis Base Sequence fungi Zinc Fingers Organ Size General Medicine biology.organism_classification Cell biology Adipose Tissue chemistry Biochemistry embryonic structures Snail Family Transcription Factors Histone deacetylase Transcription Factors |
Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
ISSN: | 1460-2083 0964-6906 |
Popis: | 15 páginas, 13 figuras, 1 tabla. The zinc-finger transcription factor SLUG (SNAI2) triggers epithelial–mesenchymal transitions (EMTs) and plays an important role in the developmental processes. Here, we show that SLUG is expressed in white adipose tissue (WAT) in humans and its expression is tightly controlled during adipocyte differentiation. Slug-deficient mice exhibit a marked deficiency in WAT size, and Slug-overexpressing mice (Combi-Slug) exhibit an increase in the WAT size. Consistent with in vivo data, Slug-deficient mouse embryonic fibroblasts (MEFs) showed a dramatically reduced capacity for adipogenesis in vitro and there was extensive lipid accumulation in Combi-Slug MEFs. The analysis of adipogenic gene expression both in vivo and in vitro showed that peroxisome proliferator-activated factor 2 (PPAR2) expression was altered. Complementation studies rescued this phenotype, indicating that WAT alterations induced by Slug are reversible. Our results further show a differential histone deacetylase recruitment to the PPAR2 promoter in a tissue- and Slug-dependent manner. Our results connect, for the first time, adipogenesis with the requirement of a critical level of an EMT regulator in mammals. This work may lead to the development of targeted drugs for the treatment of patients with obesity and/or lipodystrophy. The research is supported partially by FEDER and MEC (SAF2006-03726 and PETRI no. 95-0913.OP), Junta de Castilla y Leo´n (CSI03A05), FIS (PI050087, PI050116), Fundacio ´n de Investigacio´n MMA, Federacio´n de Cajas de Ahorro Castilla y Leo´n (I Convocatoria de Ayudas para Proyectos de Investigacio´n Biosanitaria con Ce´lulas Madre), CDTEAM project (CENIT-Ingenio 2010) and MEC Consolider-Ingenio 2010 (ref. CSD2007-0017). |
Databáze: | OpenAIRE |
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