The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis

Shi Chi Leow; Jeremie Poschmann; Peh Gek Too; Juan Yin; Roy Joseph; Craig McFarlane; Shaillay Dogra; Asim Shabbir; Philip W Ingham; Shyam Prabhakar; Melvin K S Leow; Yung Seng Lee; Kai Lyn Ng; Yap Seng Chong; Peter D Gluckman; Walter Stünkel

doi:10.1242/dev.131573

The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis

Shi Chi Leow, Jeremie Poschmann, Peh Gek Too, Juan Yin, Roy Joseph, Craig McFarlane, Shaillay Dogra, Asim Shabbir, Philip W Ingham, Shyam Prabhakar, Melvin K S Leow, Yung Seng Lee, Kai Lyn Ng, Yap Seng Chong, Peter D Gluckman, Walter Stünkel

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

43 Citations (SciVal)

Abstract

An association between impaired fetal growth and the postnatal development of obesity has been established. Here, by comparing adipocytes differentiated from mesenchymal stem cells (MSCs) taken from the umbilical cord and derived from normal and growth-restricted neonates, we identified the transcription factor SOX6 as highly expressed only in growth-restricted individuals. We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST. We further show that SOX6 interacts with β-catenin in adipocytes, suggesting an inhibition of WNT/β-catenin signaling, thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth-restricted subjects harbors hypomethylated CpGs next to SOX6 binding motifs, and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms.

Original language	English
Pages (from-to)	950-961
Number of pages	12
Journal	Development
Volume	143
Issue number	6
DOIs	https://doi.org/10.1242/dev.131573
Publication status	Published - 15 Mar 2016

Keywords

3T3 Cells
Adipocytes/drug effects
Adipogenesis/drug effects
Animals
Binding Sites
Cell Differentiation
CpG Islands/genetics
DNA Methylation/genetics
Down-Regulation/drug effects
Humans
Infant, Newborn
Infant, Small for Gestational Age/metabolism
Larva/drug effects
Lipid Metabolism/genetics
Mesenchymal Stem Cells/cytology
Mice
Mice, Inbred C57BL
Models, Biological
Obesity/genetics
Oligonucleotides, Antisense/pharmacology
Protein Binding/drug effects
Proteins/genetics
SOXD Transcription Factors/metabolism
Triglycerides/metabolism
Wnt Signaling Pathway/drug effects
Zebrafish

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1242/dev.131573

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Leow, S. C., Poschmann, J., Too, P. G., Yin, J., Joseph, R., McFarlane, C., Dogra, S., Shabbir, A., Ingham, P. W., Prabhakar, S., Leow, M. K. S., Lee, Y. S., Ng, K. L., Chong, Y. S., Gluckman, P. D., & Stünkel, W. (2016). The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis. Development, 143(6), 950-961. https://doi.org/10.1242/dev.131573

Leow, SC, Poschmann, J, Too, PG, Yin, J, Joseph, R, McFarlane, C, Dogra, S, Shabbir, A, Ingham, PW, Prabhakar, S, Leow, MKS, Lee, YS, Ng, KL, Chong, YS, Gluckman, PD & Stünkel, W 2016, 'The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis', Development, vol. 143, no. 6, pp. 950-961. https://doi.org/10.1242/dev.131573

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abstract = "An association between impaired fetal growth and the postnatal development of obesity has been established. Here, by comparing adipocytes differentiated from mesenchymal stem cells (MSCs) taken from the umbilical cord and derived from normal and growth-restricted neonates, we identified the transcription factor SOX6 as highly expressed only in growth-restricted individuals. We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST. We further show that SOX6 interacts with β-catenin in adipocytes, suggesting an inhibition of WNT/β-catenin signaling, thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth-restricted subjects harbors hypomethylated CpGs next to SOX6 binding motifs, and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms.",

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author = "Leow, {Shi Chi} and Jeremie Poschmann and Too, {Peh Gek} and Juan Yin and Roy Joseph and Craig McFarlane and Shaillay Dogra and Asim Shabbir and Ingham, {Philip W} and Shyam Prabhakar and Leow, {Melvin K S} and Lee, {Yung Seng} and Ng, {Kai Lyn} and Chong, {Yap Seng} and Gluckman, {Peter D} and Walter St{\"u}nkel",

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T1 - The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis

AU - Leow, Shi Chi

AU - Poschmann, Jeremie

AU - Too, Peh Gek

AU - Yin, Juan

AU - Joseph, Roy

AU - McFarlane, Craig

AU - Dogra, Shaillay

AU - Shabbir, Asim

AU - Ingham, Philip W

AU - Prabhakar, Shyam

AU - Leow, Melvin K S

AU - Lee, Yung Seng

AU - Ng, Kai Lyn

AU - Chong, Yap Seng

AU - Gluckman, Peter D

AU - Stünkel, Walter

PY - 2016/3/15

Y1 - 2016/3/15

N2 - An association between impaired fetal growth and the postnatal development of obesity has been established. Here, by comparing adipocytes differentiated from mesenchymal stem cells (MSCs) taken from the umbilical cord and derived from normal and growth-restricted neonates, we identified the transcription factor SOX6 as highly expressed only in growth-restricted individuals. We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST. We further show that SOX6 interacts with β-catenin in adipocytes, suggesting an inhibition of WNT/β-catenin signaling, thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth-restricted subjects harbors hypomethylated CpGs next to SOX6 binding motifs, and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms.

AB - An association between impaired fetal growth and the postnatal development of obesity has been established. Here, by comparing adipocytes differentiated from mesenchymal stem cells (MSCs) taken from the umbilical cord and derived from normal and growth-restricted neonates, we identified the transcription factor SOX6 as highly expressed only in growth-restricted individuals. We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST. We further show that SOX6 interacts with β-catenin in adipocytes, suggesting an inhibition of WNT/β-catenin signaling, thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth-restricted subjects harbors hypomethylated CpGs next to SOX6 binding motifs, and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms.

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KW - Adipocytes/drug effects

KW - Adipogenesis/drug effects

KW - Animals

KW - Binding Sites

KW - Cell Differentiation

KW - CpG Islands/genetics

KW - DNA Methylation/genetics

KW - Down-Regulation/drug effects

KW - Humans

KW - Infant, Newborn

KW - Infant, Small for Gestational Age/metabolism

KW - Larva/drug effects

KW - Lipid Metabolism/genetics

KW - Mesenchymal Stem Cells/cytology

KW - Mice

KW - Mice, Inbred C57BL

KW - Models, Biological

KW - Obesity/genetics

KW - Oligonucleotides, Antisense/pharmacology

KW - Protein Binding/drug effects

KW - Proteins/genetics

KW - SOXD Transcription Factors/metabolism

KW - Triglycerides/metabolism

KW - Wnt Signaling Pathway/drug effects

KW - Zebrafish

U2 - 10.1242/dev.131573

DO - 10.1242/dev.131573

M3 - Article

C2 - 26893351

SN - 0950-1991

VL - 143

SP - 950

EP - 961

JO - Development

JF - Development

IS - 6

ER -

The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis

Abstract

Keywords

UN SDGs

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