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Original Research

Maternal Obesity Induces Epigenetic Modifications to Facilitate Zfp423 Expression and Enhance Adipogenic Differentiation in Fetal Mice

  1. Qi-Yuan Yang1,2,
  2. Jun-Fang Liang1,
  3. Carl J. Rogers1,
  4. Jun-Xing Zhao2,
  5. Mei-Jun Zhu2,3 and
  6. Min Du1,2⇑
  1. 1Department of Animal Sciences, Washington State University, Pullman, Washington
  2. 2Developmental Biology Group, Department of Animal Science, University of Wyoming, Laramie, Wyoming
  3. 3School of Food Science, Washington State University, Pullman, Washington
  1. Corresponding author: Min Du, min.du{at}wsu.edu.
Diabetes 2013 Nov; 62(11): 3727-3735. https://doi.org/10.2337/db13-0433
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Abstract

Maternal obesity (MO) predisposes offspring to obesity and type 2 diabetes despite poorly defined mechanisms. Zfp423 is the key transcription factor committing cells to the adipogenic lineage, with exceptionally dense CpG sites in its promoter. We hypothesized that MO enhances adipogenic differentiation during fetal development through inducing epigenetic changes in the Zfp423 promoter and elevating its expression. Female mice were subjected to a control (Con) or obesogenic (OB) diet for 2 months, mated, and maintained on their diets during pregnancy. Fetal tissue was harvested at embryonic day 14.5 (E14.5), when the early adipogenic commitment is initiated. The Zfp423 expression was 3.6-fold higher and DNA methylation in the Zfp423 promoter was lower in OB compared with Con. Correspondingly, repressive histone methylation (H3K27me3) was lower in the Zfp423 promoter of OB fetal tissue, accompanied by reduced binding of enhancer of zeste 2 (EZH2). Gain- and loss-of-function analysis showed that Zfp423 regulates early adipogenic differentiation in fetal progenitor cells. In summary, MO enhanced Zfp423 expression and adipogenic differentiation during fetal development, at least partially through reducing DNA methylation in the Zfp423 promoter, which is expected to durably elevate adipogenic differentiation of progenitor cells in adult tissue, programming adiposity and metabolic dysfunction later in life.

  • Received March 18, 2013.
  • Accepted July 16, 2013.
  • © 2013 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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Maternal Obesity Induces Epigenetic Modifications to Facilitate Zfp423 Expression and Enhance Adipogenic Differentiation in Fetal Mice
Qi-Yuan Yang, Jun-Fang Liang, Carl J. Rogers, Jun-Xing Zhao, Mei-Jun Zhu, Min Du
Diabetes Nov 2013, 62 (11) 3727-3735; DOI: 10.2337/db13-0433

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Maternal Obesity Induces Epigenetic Modifications to Facilitate Zfp423 Expression and Enhance Adipogenic Differentiation in Fetal Mice
Qi-Yuan Yang, Jun-Fang Liang, Carl J. Rogers, Jun-Xing Zhao, Mei-Jun Zhu, Min Du
Diabetes Nov 2013, 62 (11) 3727-3735; DOI: 10.2337/db13-0433
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