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Cited by 152Birth, Development, and HealthEpigenetics and DNA MethylationGenetic Syndromes and Imprinting

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

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Yang, Qi-Yuan, Liang, Jun-Fang, Rogers, Carl J., Zhao, Jun-Xing, Zhu, Mei-Jun, Du, Min·2013·Diabetes
DOI 10.2337/db13-0433PMC PMC3806589
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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.

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  • Exposure to maternal obesity is associated with lower Zfp423 promoter methylation levels and increased Zfp423 gene expression in offspring adipose tissue, in alliance with enhanced adiposity.

    “In another study, exposure to maternal obesity was also associated with lower Zfp423 promoter methylation levels and increased Zfp423 gene expression in offspring adipose tissue in alliance with enhanced adiposity [140].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [140]

    The Results report lower Zfp423 promoter methylation and higher Zfp423 expression in fetal tissue from mice exposed to maternal obesity. They also report enhanced fetal adipogenic differentiation, but not increased adiposity in the studied offspring. The Discussion describes later adiposity as a likely consequence rather than a measured outcome, and the molecular findings were not established in offspring adipose tissue. (LLM, conf=0.88)

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Authors
Yang, Q.-Y., Liang, J.-F., Rogers, C. J., Zhao, J.-X., Zhu, M.-J., & Du, M.
Affiliations
  • Department of Animal Sciences, Washington State University, Pullman, Washington
  • Washington State University (US)
  • Developmental Biology Group, Department of Animal Science, University of Wyoming, Laramie, Wyoming
  • University of Wyoming (US)
Corresponding author
Du, Min
ORCID
Du, Min
Venue
Diabetes
Publisher
American Diabetes Association
Published
2013-10-18
Volume
62
Issue
11
Pages
3727-3735
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db13-0433
PMC
PMC3806589
OpenAlex
W2141229724
Cited by
152
References
2
Citations by year
2026: 4 · 2025: 12 · 2024: 6 · 2023: 8 · 2022: 15 · 2021: 11 · 2020: 15 · 2019: 18 · 2018: 6 · 2017: 17 · 2016: 13 · 2015: 18 · 2014: 9
FWCI
12.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD067449)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Keywords
maternal obesity, Zfp423, adipogenesis, epigenetic regulation, DNA methylation, H3K27me3, EZH2, fetal development, obesogenic diet, transcription factors, type 2 diabetes, developmental programming
MeSH terms
Animals, Cell Differentiation, DNA-Binding Proteins, Female, Histones, Obesity, Pregnancy, Promoter Regions, Genetic, Transcription Factors, Zinc Fingers, Adipocytes, Gene Expression Regulation, Developmental, DNA Methylation, Maternal Nutritional Physiological Phenomena, Epigenesis, Genetic, Fetal Development, Mice

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