IN UTERO EXPOSURE TO A MATERNAL HIGH FAT DIET ALTERS THE EPIGENETIC HISTONE CODE IN A MURINE MODEL

Suter, Melissa A.; MA, Jun; Vuguin, Patricia M.; Hartil, Kirsten; Fiallo, Ms. Ariana; Harris, R. Alan; Charron, Maureen J.; Aagaard, Kjersti M.

doi:10.1016/j.ajog.2014.01.045

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IN UTERO EXPOSURE TO A MATERNAL HIGH FAT DIET ALTERS THE EPIGENETIC HISTONE CODE IN A MURINE MODEL

May 2014
By Suter, Melissa A. ; MA, Jun ; Vuguin, Patricia M. ; ...
http://dx.doi.org/10.1016/j.ajog.2014.01.045
Source: Am J Obstet Gynecol. 2014; 210(5):463.e1-463.e11.

[PDF-1.40 MB]

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Details:

Alternative Title:

Am J Obstet Gynecol
Personal Author:

Suter, Melissa A. ; MA, Jun ; Vuguin, Patricia M. ; Hartil, Kirsten ; Fiallo, Ms. Ariana ; ... More +

Suter, Melissa A. ; MA, Jun ; Vuguin, Patricia M. ; Hartil, Kirsten ; Fiallo, Ms. Ariana ; Harris, R. Alan ; Charron, Maureen J. ; Aagaard, Kjersti M. Less -
Description:

Objective

Data from animal models show that in utero exposure to a maternal high fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering risk of adult disease. Because mice heterozygous for GLUT4 (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to a high fat diet in utero, we sought to analyze the genome-wide epigenetic changes which occur in the fetal liver in susceptible offspring.

Study Design

WT and Glut4+/− (G4+/−) offspring of WT mothers exposed either to a control or a HF diet in utero were studied. Immunoblotting was used to measure hepatic histone modifications of fetal and 5 week animals. Chromatin immunoprecipitation (ChIP) followed by hybridization to chip arrays (ChIP on chip) was utilized to detect genome-wide changes of histone modifications with HFD exposure.

Results

We found that levels of hepatic H3K14ac and H3K9me3 significantly increased with HFD exposure in WT and G4+/− fetal and 5 week offspring. Pathway analysis of our ChIP on chip data reveal differential H3K14ac and H3K9me3 enrichment along pathways which regulate lipid metabolism, specifically in the promoter regions of Pparg, Ppara, Rxra and Rora.

Conclusion

We conclude that HFD exposure in utero is associated with functional alterations to fetal hepatic histone modifications in both WT and G4+/− offspring, some which persist up to 5 weeks of age.
Subjects:

[+]

Acetylation Animals Article Comparative Genomic Hybridization Developmental Origins Of Adult Disease Diet, High-Fat Dietary Fats Epigenesis, Genetic Female Gene Expression Regulation, Developmental Genetic Predisposition To Disease Glucose Transporter Type 4 GLUT4 H3K9me3 H3K14ac Histone Code Histones Liver Metabolic Syndrome X Mice Models, Animal Pregnancy Prenatal Exposure Delayed Effects Prenatal Nutritional Physiological Phenomena
Source:

Am J Obstet Gynecol. 2014; 210(5):463.e1-463.e11.
Pubmed ID:

24793723
Pubmed Central ID:

PMC4368445
Document Type:

Journal Article
Funding:

DP2 OD001500/OD/NIH HHS/United States ; DP2O D001500-01/DP/NCCDPHP CDC HHS/United States ; K12 GM084897/GM/NIGMS NIH HHS/United States ; L40 HD051105/HD/NICHD NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; ... More +

DP2 OD001500/OD/NIH HHS/United States ; DP2O D001500-01/DP/NCCDPHP CDC HHS/United States ; K12 GM084897/GM/NIGMS NIH HHS/United States ; L40 HD051105/HD/NICHD NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; P60 DK020541/DK/NIDDK NIH HHS/United States ; R01 DK089201/DK/NIDDK NIH HHS/United States ; R21 DK081194/DK/NIDDK NIH HHS/United States Less -
Volume:

210
Issue:

5
Collection(s):

CDC Public Access
Main Document Checksum:

[+]

urn:sha256:8171b936630be95e8e90364e9993029a97d86f57b0c2aad094b1f3923702aee5
Download URL:

https://stacks.cdc.gov/view/cdc/30337/cdc_30337_DS1.pdf
File Type:

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