Intrauterine growth restriction and docosahexanoic acid supplementation alter DNA methylation of the peroxisome proliferator activated receptor gamma promoter 2 in rat visceral adipose tissue

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Title Intrauterine growth restriction and docosahexanoic acid supplementation alter DNA methylation of the peroxisome proliferator activated receptor gamma promoter 2 in rat visceral adipose tissue
Publication Type thesis
School or College College of Health
Department Nutrition & Integrative Physiology
Author Heglas, Andrea Marie
Date 2012-08
Description Intrauterine growth restriction (IUGR) increases the risk for visceral obesity and metabolic complications, with males more affected. We have shown that IUGR increases visceral adipose tissue (VAT) and mRNA levels of the pro-adipogenic transcription factor, PPARγ2, in adolescent male rats but not females. Increased PPARγ2 expression may be influenced by epigenetics. Epigenetic modifications include DNA methylation, with decreased methylation commonly associated with increased expression. PPARγ2 expression is also affected by the presence its endogenous ligand, docosahexanoic acid (DHA). We have shown that maternal DHA supplementation normalizes PPARγ2 mRNA in male rats. The effect of IUGR and maternal DHA supplementation on DNA methylation of PPARγ is unknown. We hypothesize that IUGR will decrease DNA methylation of PPARγ P2 in males and maternal DHA supplementation will correct these changes. We further hypothesize that neither IUGR nor maternal DHA supplementation will alter DNA methylation of PPARγ P2 in females or of PPARγ P1 in males and females. IUGR was induced by bilateral uterine artery ligation on day E19.5 of gestation. Maternal rats were fed a regular diet or diet containing 0.1% DHA. VAT was harvested at day 21 of life (d21) from control, IUGR, DHA, and IUGR+DHA male and female rats. PPARγ2 mRNA levels were analyzed using RT-PCR. Nucleotide specific DNA methylation of 21 sites within PPARγ P1 and 5 sites within P2 were analyzed using bisulfite modification.
Type Text
Publisher University of Utah
Subject Adipose tissue; DNA methylation; Docosahexanoic acid; Epigenetics; Intrauterine growth restriction; PPAR-gamm
Subject LCSH Fetal growth retardation -- Physiological aspects
Dissertation Institution University of Utah
Dissertation Name Master of Science
Language eng
Rights Management Copyright © Andrea Marie Heglas 2012
Format application/pdf
Format Medium application/pdf
Format Extent 798,278 bytes
Identifier etd3/id/1842
Source Original in Marriott Library Special Collections, QP6.5 2012 .H43
ARK ark:/87278/s6w95r14
Setname ir_etd
ID 195530
Reference URL https://collections.lib.utah.edu/ark:/87278/s6w95r14
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