Adipose tissue mass is modulated by SLUG (SNAI2).
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 gamma2 (PPARgamma2) 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 PPARgamma2 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.
Pérez-Mancera
Pedro Antonio
PA
Experimental Therapeutics and Translational Oncology Program, Instituto de Biologia Molecular y Celular del Cancer, Salamanca, Spain.
Bermejo-Rodríguez
Camino
C
González-Herrero
Inés
I
Herranz
Michel
M
Flores
Teresa
T
Jiménez
Rafael
R
Sánchez-García
Isidro
I
D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers / Q000235:genetics
D017931:DNA Primers; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors