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The ZEB1 Transcription Factor Is a Novel Repressor of Adiposity in Female Mice

BACKGROUND: Four genome-wide association studies mapped an “obesity” gene to human chromosome 10p11–12. As the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor is encoded by the TCF8 gene located in that region, and as it influences the differentiation of various mesodermal lineages,...

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Autores principales: Saykally, Jessica N., Dogan, Soner, Cleary, Margot P., Sanders, Michel M.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794530/
https://www.ncbi.nlm.nih.gov/pubmed/20041147
http://dx.doi.org/10.1371/journal.pone.0008460
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author Saykally, Jessica N.
Dogan, Soner
Cleary, Margot P.
Sanders, Michel M.
author_facet Saykally, Jessica N.
Dogan, Soner
Cleary, Margot P.
Sanders, Michel M.
author_sort Saykally, Jessica N.
collection PubMed
description BACKGROUND: Four genome-wide association studies mapped an “obesity” gene to human chromosome 10p11–12. As the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor is encoded by the TCF8 gene located in that region, and as it influences the differentiation of various mesodermal lineages, we hypothesized that ZEB1 might also modulate adiposity. The goal of these studies was to test that hypothesis in mice. METHODOLOGY/PRINCIPAL FINDINGS: To ascertain whether fat accumulation affects ZEB1 expression, female C57BL/6 mice were fed a regular chow diet (RCD) ad libitum or a 25% calorie-restricted diet from 2.5 to 18.3 months of age. ZEB1 mRNA levels in parametrial fat were six to ten times higher in the obese mice. To determine directly whether ZEB1 affects adiposity, wild type (WT) mice and mice heterozygous for TCF8 (TCF8+/−) were fed an RCD or a high-fat diet (HFD) (60% calories from fat). By two months of age on an HFD and three months on an RCD, TCF8+/− mice were heavier than WT controls, which was attributed by Echo MRI to increased fat mass (at three months on an HFD: 0.517±0.081 total fat/lean mass versus 0.313±0.036; at three months on an RCD: 0.175±0.013 versus 0.124±0.012). No differences were observed in food uptake or physical activity, suggesting that the genotypes differ in some aspect of their metabolic activity. ZEB1 expression also increases during adipogenesis in cell culture. CONCLUSION/SIGNIFICANCE: These results show for the first time that the ZEB1 transcription factor regulates the accumulation of adipose tissue. Furthermore, they corroborate the genome-wide association studies that mapped an “obesity” gene at chromosome 10p11–12.
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spelling pubmed-27945302009-12-30 The ZEB1 Transcription Factor Is a Novel Repressor of Adiposity in Female Mice Saykally, Jessica N. Dogan, Soner Cleary, Margot P. Sanders, Michel M. PLoS One Research Article BACKGROUND: Four genome-wide association studies mapped an “obesity” gene to human chromosome 10p11–12. As the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor is encoded by the TCF8 gene located in that region, and as it influences the differentiation of various mesodermal lineages, we hypothesized that ZEB1 might also modulate adiposity. The goal of these studies was to test that hypothesis in mice. METHODOLOGY/PRINCIPAL FINDINGS: To ascertain whether fat accumulation affects ZEB1 expression, female C57BL/6 mice were fed a regular chow diet (RCD) ad libitum or a 25% calorie-restricted diet from 2.5 to 18.3 months of age. ZEB1 mRNA levels in parametrial fat were six to ten times higher in the obese mice. To determine directly whether ZEB1 affects adiposity, wild type (WT) mice and mice heterozygous for TCF8 (TCF8+/−) were fed an RCD or a high-fat diet (HFD) (60% calories from fat). By two months of age on an HFD and three months on an RCD, TCF8+/− mice were heavier than WT controls, which was attributed by Echo MRI to increased fat mass (at three months on an HFD: 0.517±0.081 total fat/lean mass versus 0.313±0.036; at three months on an RCD: 0.175±0.013 versus 0.124±0.012). No differences were observed in food uptake or physical activity, suggesting that the genotypes differ in some aspect of their metabolic activity. ZEB1 expression also increases during adipogenesis in cell culture. CONCLUSION/SIGNIFICANCE: These results show for the first time that the ZEB1 transcription factor regulates the accumulation of adipose tissue. Furthermore, they corroborate the genome-wide association studies that mapped an “obesity” gene at chromosome 10p11–12. Public Library of Science 2009-12-24 /pmc/articles/PMC2794530/ /pubmed/20041147 http://dx.doi.org/10.1371/journal.pone.0008460 Text en Saykally et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Saykally, Jessica N.
Dogan, Soner
Cleary, Margot P.
Sanders, Michel M.
The ZEB1 Transcription Factor Is a Novel Repressor of Adiposity in Female Mice
title The ZEB1 Transcription Factor Is a Novel Repressor of Adiposity in Female Mice
title_full The ZEB1 Transcription Factor Is a Novel Repressor of Adiposity in Female Mice
title_fullStr The ZEB1 Transcription Factor Is a Novel Repressor of Adiposity in Female Mice
title_full_unstemmed The ZEB1 Transcription Factor Is a Novel Repressor of Adiposity in Female Mice
title_short The ZEB1 Transcription Factor Is a Novel Repressor of Adiposity in Female Mice
title_sort zeb1 transcription factor is a novel repressor of adiposity in female mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2794530/
https://www.ncbi.nlm.nih.gov/pubmed/20041147
http://dx.doi.org/10.1371/journal.pone.0008460
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