Journal article
Consuming a Western diet for two weeks suppresses fetal genes in mouse hearts
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.306(8), pp.R519-R526
Fetal and Neonatal Programming: Epigenetic Modification of Phenotype
04/15/2014
Handle:
https://hdl.handle.net/2376/109843
PMCID: PMC4121485
PMID: 24523346
Abstract
Diets high in sugar and saturated fat (Western diet) contribute to obesity and pathophysiology of metabolic syndrome. A common physiological response to obesity is hypertension, which induces cardiac remodeling and hypertrophy. Hypertrophy is regulated at the level of chromatin by repressor element 1-silencing transcription factor (REST), and pathological hypertrophy is associated with reexpression of a fetal cardiac gene program. Reactivation of fetal genes is commonly observed in hypertension-induced hypertrophy; however, this response is blunted in diabetic hearts, partially due to upregulation of the posttranslational modification
O
-linked-β-
N
-acetylglucosamine (
O
-GlcNAc) to proteins by
O
-GlcNAc transferase (OGT). OGT and
O
-GlcNAc are found in chromatin-modifying complexes, but it is unknown whether they play a role in Western diet-induced hypertrophic remodeling. Therefore, we investigated the interactions between
O
-GlcNAc, OGT, and the fetal gene-regulating transcription factor complex REST/mammalian switch-independent 3A/histone deacetylase (HDAC). Five-week-old male C57BL/6 mice were fed a Western (
n
= 12) or control diet (
n
= 12) for 2 wk to examine the early hypertrophic response. Western diet-fed mice exhibited fasting hyperglycemia and increased body weight (
P
< 0.05). As expected for this short duration of feeding, cardiac hypertrophy was not yet evident. We found that REST is
O
-GlcNAcylated and physically interacts with OGT in mouse hearts. Western blot analysis showed that HDAC protein levels were not different between groups; however, relative to controls, Western diet hearts showed increased REST and decreased ANP and skeletal α-actin. Transcript levels of HDAC2 and cardiac α-actin were decreased in Western diet hearts. These data suggest that REST coordinates regulation of diet-induced hypertrophy at the level of chromatin.
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Details
- Title
- Consuming a Western diet for two weeks suppresses fetal genes in mouse hearts
- Creators
- Heidi M Medford - Graduate Program in Pharmaceutical Sciences, Washington State University, Spokane, Washington; andEmily J Cox - Graduate Program in Pharmaceutical Sciences, Washington State University, Spokane, Washington; andLindsey E Miller - Section of Clinical Pharmacology, College of Pharmacy, Washington State University, Spokane, WashingtonSusan A Marsh - Section of Clinical Pharmacology, College of Pharmacy, Washington State University, Spokane, Washington
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.306(8), pp.R519-R526
- Academic Unit
- Nutrition and Exercise Physiology, Department of; Pharmaceutical Sciences, Department of
- Series
- Fetal and Neonatal Programming: Epigenetic Modification of Phenotype
- Publisher
- American Physiological Society; Bethesda, MD
- Identifiers
- 99900547277301842
- Language
- English
- Resource Type
- Journal article