title: Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes.
abstract: 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.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.
authors.forename: Zivjena
authors.initials: Z
authors.lastname: Vucetic
authors.forename: Jessica
authors.initials: J
authors.lastname: Kimmel
authors.forename: Kathy
authors.initials: K
authors.lastname: Totoki
authors.forename: Emily
authors.initials: E
authors.lastname: Hollenbeck
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Reyes
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019175:DNA Methylation / Q000187:drug effects*; D004041:Dietary Fats / Q000494:pharmacology*; D004298:Dopamine / Q000235:genetics* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D002149:Energy Intake / Q000235:genetics; D005260:Female; D005518:Food Preferences / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000187:drug effects / Q000502:physiology; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018847:Opioid Peptides / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011957:Receptors, Opioid / Q000235:genetics* / Q000378:metabolism; D012201:Reward
chemical_list: D004041:Dietary Fats; D050483:Dopamine Plasma Membrane Transport Proteins; D018847:Opioid Peptides; D011957:Receptors, Opioid; D004298:Dopamine