The Winged Helix Transcription Factor Foxa3 Regulates Adipocyte Differentiation and Depot-Selective Fat Tissue Expansion

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Published inMolecular and Cellular Biology Vol. 33; no. 17; pp. 3392 - 3399
Main Authors Xu, Lingyan, Panel, Valentine, Ma, Xinran, Du, Chen, Hugendubler, Lynne, Gavrilova, Oksana, Liu, Alice, McLaughlin, Tracey, Kaestner, Klaus H., Mueller, Elisabetta
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 01.09.2013
Taylor & Francis
Subjects
3T3-L1 Cells
adipocytes
Adipocytes - cytology
Adipocytes - metabolism
Adipogenesis
adipose tissue
Adipose Tissue - growth & development
Adipose Tissue - metabolism
Adult
Animals
CCAAT-Enhancer-Binding Protein-beta - metabolism
CCAAT-Enhancer-Binding Protein-delta - metabolism
Diet, High-Fat
epididymis
Female
Gene Deletion
Gene Expression Regulation, Developmental
Hepatocyte Nuclear Factor 3-gamma - genetics
Hepatocyte Nuclear Factor 3-gamma - metabolism
Humans
Insulin Resistance - genetics
Mice
Mice, Inbred C57BL
Middle Aged
Obesity - genetics
Obesity - metabolism
peroxisome proliferator-activated receptor gamma
PPAR gamma - genetics
PPAR gamma - metabolism
RNA
RNA Interference
transcription (genetics)
Transcriptional Activation
Young Adult
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Abstract OA  Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to MCB .asm.org, visit: MCB       
AbstractList Conversion of mesenchymal stem cells into terminally differentiated adipocytes progresses sequentially through regulated transcriptional steps. While it is clear that the late phases of adipocyte maturation are governed by the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), less is known about the transcriptional control of the initial stages of differentiation. To identify early regulators, we performed a small interfering RNA (siRNA) screen of Forkhead-box genes in adipocytes and show here for the first time that the winged helix factor Foxa3 promotes adipocyte differentiation by cooperating with C/EBPβ and -δ to transcriptionally induce PPARγ expression. Furthermore, we demonstrate that mice with genetic ablation of Foxa3 have a selective decrease in epididymal fat depot and a cell-autonomous defect to induce PPARγ specifically in their visceral adipocytes. In obese subjects, FOXA3 is differentially expressed in visceral and subcutaneous adipose depots. Overall, our study implicates Foxa3 in the regulation of adipocyte differentiation and depot-selective adipose tissue expansion.
Conversion of mesenchymal stem cells into terminally differentiated adipocytes progresses sequentially through regulated transcriptional steps. While it is clear that the late phases of adipocyte maturation are governed by the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma ), less is known about the transcriptional control of the initial stages of differentiation. To identify early regulators, we performed a small interfering RNA (siRNA) screen of Forkhead-box genes in adipocytes and show here for the first time that the winged helix factor Foxa3 promotes adipocyte differentiation by cooperating with C/EBP beta and - delta to transcriptionally induce PPAR gamma expression. Furthermore, we demonstrate that mice with genetic ablation of Foxa3 have a selective decrease in epididymal fat depot and a cell-autonomous defect to induce PPAR gamma specifically in their visceral adipocytes. In obese subjects, FOXA3 is differentially expressed in visceral and subcutaneous adipose depots. Overall, our study implicates Foxa3 in the regulation of adipocyte differentiation and depot-selective adipose tissue expansion.
OA  Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to MCB .asm.org, visit: MCB       
Conversion of mesenchymal stem cells into terminally differentiated adipocytes progresses sequentially through regulated transcriptional steps. While it is clear that the late phases of adipocyte maturation are governed by the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), less is known about the transcriptional control of the initial stages of differentiation. To identify early regulators, we performed a small interfering RNA (siRNA) screen of Forkhead-box genes in adipocytes and show here for the first time that the winged helix factor Foxa3 promotes adipocyte differentiation by cooperating with C/EBPβ and -δ to transcriptionally induce PPARγ expression. Furthermore, we demonstrate that mice with genetic ablation of Foxa3 have a selective decrease in epididymal fat depot and a cell-autonomous defect to induce PPARγ specifically in their visceral adipocytes. In obese subjects, FOXA3 is differentially expressed in visceral and subcutaneous adipose depots. Overall, our study implicates Foxa3 in the regulation of adipocyte differentiation and depot-selective adipose tissue expansion.Conversion of mesenchymal stem cells into terminally differentiated adipocytes progresses sequentially through regulated transcriptional steps. While it is clear that the late phases of adipocyte maturation are governed by the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), less is known about the transcriptional control of the initial stages of differentiation. To identify early regulators, we performed a small interfering RNA (siRNA) screen of Forkhead-box genes in adipocytes and show here for the first time that the winged helix factor Foxa3 promotes adipocyte differentiation by cooperating with C/EBPβ and -δ to transcriptionally induce PPARγ expression. Furthermore, we demonstrate that mice with genetic ablation of Foxa3 have a selective decrease in epididymal fat depot and a cell-autonomous defect to induce PPARγ specifically in their visceral adipocytes. In obese subjects, FOXA3 is differentially expressed in visceral and subcutaneous adipose depots. Overall, our study implicates Foxa3 in the regulation of adipocyte differentiation and depot-selective adipose tissue expansion.
Author Tracey McLaughlin
Xinran Ma
Alice Liu
Elisabetta Mueller
Oksana Gavrilova
Chen Du
Klaus H. Kaestner
Valentine Panel
Lingyan Xu
Lynne Hugendubler
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L.X., V.P., and X.M. contributed equally to this article.
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Snippet OA  Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+...
Conversion of mesenchymal stem cells into terminally differentiated adipocytes progresses sequentially through regulated transcriptional steps. While it is...
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SubjectTerms 3T3-L1 Cells
adipocytes
Adipocytes - cytology
Adipocytes - metabolism
Adipogenesis
adipose tissue
Adipose Tissue - growth & development
Adipose Tissue - metabolism
Adult
Animals
CCAAT-Enhancer-Binding Protein-beta - metabolism
CCAAT-Enhancer-Binding Protein-delta - metabolism
Diet, High-Fat
epididymis
Female
Gene Deletion
Gene Expression Regulation, Developmental
Hepatocyte Nuclear Factor 3-gamma - genetics
Hepatocyte Nuclear Factor 3-gamma - metabolism
Humans
Insulin Resistance - genetics
Mice
Mice, Inbred C57BL
Middle Aged
Obesity - genetics
Obesity - metabolism
peroxisome proliferator-activated receptor gamma
PPAR gamma - genetics
PPAR gamma - metabolism
RNA
RNA Interference
transcription (genetics)
Transcriptional Activation
Young Adult
Title The Winged Helix Transcription Factor Foxa3 Regulates Adipocyte Differentiation and Depot-Selective Fat Tissue Expansion
URI http://mcb.asm.org/content/33/17/3392.abstract
https://www.tandfonline.com/doi/abs/10.1128/MCB.00244-13
https://www.ncbi.nlm.nih.gov/pubmed/23798556
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