Document Detail


Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes.
MedLine Citation:
PMID:  20685869     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Maternal obesity during pregnancy increases the risk of obesity in the offspring. Obesity, arising from an imbalance of energy intake and expenditure, can be driven by the ingestion of palatable [high fat (HF), high sugar], energy-dense foods. Dopamine and opioid circuitry are neural substrates associated with reward that can affect animals' preference for palatable foods. Using a mouse model, the long-term effect of maternal consumption of a HF diet on dopamine and opioid gene expression within the mesocorticolimbic reward circuitry and hypothalamus of the offspring was investigated. Mice from dams fed a HF diet during pregnancy and lactation showed an increased preference for sucrose and fat. Gene expression, measured using quantitative real-time PCR, revealed a significant approximately 3- to 10-fold up-regulation of dopamine reuptake transporter (DAT) in the ventral tegmental area, nucleus accumbens, and prefrontal cortex and a down-regulation of DAT in the hypothalamus. Additionally, expression of both μ-opioid receptor (MOR) and preproenkephalin (PENK) was increased in nucleus accumbens, prefrontal cortex, and hypothalamus of mice from dams that consumed the HF diet. Epigenetic mechanisms have been associated with long-term programming of gene expression after various in utero insults. We observed global and gene-specific (DAT, MOR, and PENK) promoter DNA hypomethylation in the brains of offspring from dams that consumed the HF diet. These data demonstrate that maternal consumption of a HF diet can change the offsprings' epigenetic marks (DNA hypomethylation) in association with long-term alterations in gene expression (dopamine and opioids) and behavior (preference for palatable foods).
Authors:
Zivjena Vucetic; Jessica Kimmel; Kathy Totoki; Emily Hollenbeck; Teresa M Reyes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-04
Journal Detail:
Title:  Endocrinology     Volume:  151     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-22     Completed Date:  2010-11-04     Revised Date:  2012-04-27    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4756-64     Citation Subset:  AIM; IM    
Affiliation:
University of Pennsylvania School of Medicine, Department of Pharmacology, Institute for Translational Medicine and Therapeutics, School of Medicine, 805 Biomedical Research Building II/III, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104-6160, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
DNA Methylation / drug effects*
Dietary Fats / pharmacology*
Dopamine / genetics*,  metabolism
Dopamine Plasma Membrane Transport Proteins / genetics,  metabolism
Energy Intake / genetics
Female
Food Preferences / physiology
Gene Expression / drug effects
Hypothalamus / metabolism
Male
Maternal Nutritional Physiological Phenomena / drug effects,  physiology
Maternal-Fetal Exchange / drug effects,  genetics
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Opioid Peptides / genetics*,  metabolism
Pregnancy
Receptors, Opioid / genetics*,  metabolism
Reward
Grant Support
ID/Acronym/Agency:
DK064086/DK/NIDDK NIH HHS; K01 DK064086-06/DK/NIDDK NIH HHS; MH087978/MH/NIMH NIH HHS; R01 MH087978-01A1/MH/NIMH NIH HHS; R01 MH087978-02/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Dietary Fats; 0/Dopamine Plasma Membrane Transport Proteins; 0/Opioid Peptides; 0/Receptors, Opioid
Comments/Corrections

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