Journal Article

Adipose tissue mass is modulated by <i>SLUG</i> (<i>SNAI2</i>)

Pedro Antonio Pérez-Mancera, Camino Bermejo-Rodríguez, Inés González-Herrero, Michel Herranz, Teresa Flores, Rafael Jiménez and Isidro Sánchez-García

in Human Molecular Genetics

Volume 16, issue 23, pages 2972-2986
Published in print December 2007 | ISSN: 0964-6906
Published online September 2007 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddm278
Adipose tissue mass is modulated by SLUG (SNAI2)

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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 γ2 (PPARγ2) 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 PPARγ2 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.

Journal Article.  8837 words.  Illustrated.

Subjects: Genetics and Genomics

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