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.
Department of Pharmacology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Neuropsychopharmacology. 2014 Mar;39(4):801-10. doi: 10.1038/npp.2013.193. Epub 2013 Aug 8.
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.
孕期母体肥胖会增加后代肥胖的风险,部分原因是其对发育中大脑的影响。先前的研究表明,母亲在围产期食用非常美味的食物会影响后代味觉偏好的形成,并改变中枢神经系统(CNS)奖励系统内的基因表达。阿片类物质会刺激脂肪和碳水化合物的消耗,而这些能量密集型食物的过度消耗会增加肥胖的风险。目前仍不清楚这种风险是否可以在妊娠前传递给后代,或者是否完全是妊娠暴露影响了后代大脑的发育。利用胚胎移植实验设计,从肥胖或对照孕鼠中获得 2 细胞胚胎,并将其移植到肥胖或对照孕鼠中。在成年和晚期胚胎大脑的下丘脑和奖励回路(腹侧被盖区、前额叶皮层和伏隔核)中评估了μ-阿片受体(MOR)、前强啡肽原(PENK)和多巴胺转运体的表达。妊娠前肥胖改变了 MOR 和 PENK 的表达水平,雄性受影响的程度相对大于雌性。这些数据首次表明,妊娠前肥胖,除了妊娠期间肥胖外,还可以对大脑奖励系统进行编程。