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

Year: 2016
Type: article
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.
Source: Development
DOI: 10.1242/dev.131573
Authors: 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
Institutions: Agency for Science, Technology and Research, Singapore Institute for Clinical Sciences, Genome Institute of Singapore, Nanyang Technological University, National University of Singapore, National University Hospital, Institute of Molecular and Cell Biology, Tan Tock Seng Hospital, University of Auckland
Language: English
Field: Medicine
Open Access status: bronze
OpenAlex ID: W2291357366
FWCI: 6.731
Cites: 41
Cited by: 52
Related to: 10