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Cited by 172Birth, Development, and HealthEpigenetics and DNA MethylationLipid metabolism and biosynthesis

Maternal Obesity Enhances White Adipose Tissue Differentiation and Alters Genome-Scale DNA Methylation in Male Rat Offspring

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Borengasser, Sarah J., Zhong, Ying, Kang, Ping, Lindsey, Forrest, Ronis, Martin J. J., Badger, Thomas M., Gomez-Acevedo, Horacio, Shankar, Kartik·2013·Endocrinology
DOI 10.1210/en.2012-2255PMC PMC3800750
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Abstract

The risk of obesity (OB) in adulthood is strongly influenced by maternal body composition. Here we examined the hypothesis that maternal OB influences white adipose tissue (WAT) transcriptome and increases propensity for adipogenesis in the offspring, prior to the development of OB, using an established model of long-term metabolic programming. Employing an overfeeding-based rat model, in which exposure to OB is limited to preconception and gestation alone, we conducted global transcriptomic profiling in WAT, and gene/protein expression analysis of lipogenic and adipogenic pathways and examined adipogenic differentiation of WAT stromal-vascular cells ex vivo. Using reduced representation bisulfite sequencing we also evaluated genome-scale changes in DNA methylation in offspring WAT. Maternal OB led to extensive changes in expression of genes (±1.8-fold, P ≤ .05), revealing a distinct up-regulation of lipogenic pathways in WAT. mRNA expression of a battery of sterol regulatory element-binding protein-1-regulated genes was increased in OB-dam offspring, which were confirmed by immunoblotting. In conjunction with lipogenic gene expression, OB-dam offspring showed increased glucose transporter-4 mRNA/protein expression and greater AKT phosphorylation following acute insulin challenge, suggesting sensitization of insulin signaling in WAT. Offspring of OB dams also exhibited increased in vivo expression of adipogenic regulators (peroxisome proliferator-activated receptor-γ, CCAAT enhancer binding protein α [C/EBP-α] and C/EBP-β), associated with greater ex vivo differentiation of WAT stromal-vascular cells. These transcriptomic changes were associated with alterations in DNA methylation of CpG sites and CGI shores, proximal to developmentally important genes, including key pro-adipogenic factors (Zfp423 and C/EBP-β). Our findings strongly suggest that the maternal OB in utero alters adipocyte commitment and differentiation via epigenetic mechanisms.

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  • In the WAT of males from obese rats, there are alterations in DNA methylation of CpG sites proximal to C/EBP-β and Zfp423 genes, which is consistent with increased expression of key adipogenic regulators PPAR-γ, C/EBP-α, and C/EBP-β.

    “In the WAT of males from obese rats, there are alterations in DNA methylation of CpG sites proximal to C/EBP-β and Zfp423 genes, which encode key transcriptional factors initiating adipogenic commitment and is consistent with the increased expression of key adipogenic regulators, PPAR-γ, C/EBP-α, and C/EBP-β [139].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [139]

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Authors
Borengasser, S. J., Zhong, Y., Kang, P., Lindsey, F., Ronis, M. J. J., Badger, T. M., Gomez-Acevedo, H., & Shankar, K.
Affiliations
  • Arkansas Children's Nutrition Center (US)
  • Arkansas Children's Nutrition Center (S.J.B., Y.Z., P.K., F.L., M.J.J.R., T.M.B., H.G-A., K.S.), University of Arkansas for Medical Sciences, Little Rock, Arkansas 72202
Corresponding author
Shankar, Kartik
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2013-11-01
Volume
154
Issue
11
Pages
4113-4125
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2012-2255
PMC
PMC3800750
OpenAlex
W2093680541
Cited by
172
References
4
Citations by year
2026: 6 · 2025: 9 · 2024: 5 · 2023: 11 · 2022: 13 · 2021: 12 · 2020: 12 · 2019: 24 · 2018: 12 · 2017: 18 · 2016: 24 · 2015: 15 · 2014: 11
FWCI
15.51
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Agriculture
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK084225)
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 › Biochemistry › Lipid metabolism and biosynthesis
Keywords
maternal obesity, white adipose tissue, adipogenesis, DNA methylation, epigenetic programming, metabolic programming, SREBP1, glucose transporter 4, insulin signaling, PPARγ, C/EBPβ, Zfp423, CpG islands, stromal vascular cells, offspring, rat model
MeSH terms
Animals, Female, Gene Expression Regulation, Insulin, Male, Obesity, Pregnancy, Signal Transduction, Genome, Rats, Sprague-Dawley, DNA Methylation, Lipogenesis, Rats, Adipose Tissue, White, Transcriptome

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