Obesity at conception programs the opioid system in the offspring brain.
Maternal obesity during pregnancy increases the risk for offspring obesity, in part through effects on the developing brain. Previous research has shown that perinatal consumption of highly palatable foods by the mother can influence the development of offspring taste preferences and alter gene expression within the central nervous system (CNS) reward system. Opioids stimulate consumption of both fats and carbohydrates, and overconsumption of these energy dense foods increases the risk for obesity. What has remained unclear is whether this risk can be transmitted to the offspring before gestation or if it is wholly the gestational exposure that affects offspring brain development. Utilizing an embryo transfer experimental design, 2-cell embryos were obtained from obese or control dams, and transferred to obese or control gestational carriers. Expression of the mu-opioid receptor (MOR), preproenkephalin (PENK), and the dopamine transporter was evaluated in the hypothalamus and reward circuitry (ventral tegmental area, prefrontal cortex, and nucleus accumbens) in adult and late embryonic brains. Obesity before pregnancy altered expression levels of both MOR and PENK, with males relatively more affected than females. These data are the first to demonstrate that obesity at conception, in addition to during gestation, can program the brain reward system.
1] Department of Pharmacology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA [2] Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Nicola M
NM
Grissom
Department of Pharmacology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Randolph
R
Lyde
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Lori
L
Christ
Department of Obstetric and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Isaac E
IE
Sasson
1] Department of Pharmacology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA [2] Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
JesseLea
J
Carlin
Department of Obstetric and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Alexa P
AP
Vitins
1] Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA [2] Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA [3] Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Rebecca A
RA
Simmons
1] Department of Pharmacology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA [2] Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Teresa M
TM
Reyes
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D019924:Embryo Disposition; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D024282:Genes, sry / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D033261:Maternal-Fetal Relations; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D004745:Enkephalins; D011498:Protein Precursors; D017450:Receptors, Opioid, mu; D049452:Green Fluorescent Proteins; C033660:preproenkephalin