Ramírez-López María Teresa, Vázquez Mariam, Lomazzo Ermelinda, Hofmann Clementine, Blanco Rosario Noemi, Alén Francisco, Antón María, Decara Juan, Arco Rocío, Orio Laura, Suárez Juan, Lutz Beat, Gómez de Heras Raquel, Bindila Laura, Rodríguez de Fonseca Fernando
Departamento de Psicobiología. Facultad de Psicología, Universidad Complutense de Madrid. Campus de Somosaguas s/n, Pozuelo de Alarcón, Madrid, Spain.
IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
PLoS One. 2017 Mar 27;12(3):e0174307. doi: 10.1371/journal.pone.0174307. eCollection 2017.
Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring. We focused on brain structures involved in metabolism, feeding behavior, as well as emotional and cognitive responses. Female Wistar rats were assigned during the entire pregnancy to either control diet (C) or restriction diet (R), consisting of a 20% calorie-restricted diet. Weight gain and caloric intake of rat dams were monitored and birth outcomes were assessed. 2-AG, AA and NAE levels were measured in hypothalamus, hippocampus and olfactory bulb of the offspring. R dams displayed lower gain weight from the middle pregnancy and consumed less calories during the entire pregnancy. Offspring from R dams were underweight at birth, but litter size was unaffected. In hypothalamus, R male offspring displayed decreased levels of AA and OEA, with no change in the levels of the endocannabinoids 2-AG and AEA. R female exhibited decreased 2-AG and PEA levels. The opposite was found in the hippocampus, where R male displayed increased 2-AG and AA levels, and R female exhibited elevated levels of AEA, AA and PEA. In the olfactory bulb, only R female presented decreased levels of AEA, AA and PEA. Therefore, a moderate diet restriction during the entire pregnancy alters differentially the endocannabinoids and/or endocannabinoid-related lipids in hypothalamus and hippocampus of the underweight offspring, similarly in both sexes, whereas sex-specific alterations occur in the olfactory bulb. Consequently, endocannabinoid and endocannabinoid-related lipid signaling alterations might be involved in the long-term and sexual dimorphism effects commonly observed after undernutrition and low birth weight.
孕期营养不足与日后生活中代谢和行为改变的易感性增加有关。内源性大麻素系统可能在这些过程中发挥重要作用。因此，我们研究了母体适度热量限制饮食对新生大鼠后代大脑中内源性大麻素2-花生四烯酸甘油酯（2-AG）、花生四烯酸（AA）以及N-酰基乙醇胺（NAEs）花生四烯酸乙醇胺（AEA）、油酰乙醇胺（OEA）和棕榈酰乙醇胺（PEA）水平的影响。我们重点关注参与代谢、摄食行为以及情绪和认知反应的脑结构。雌性Wistar大鼠在整个孕期被分配到对照饮食（C）组或限制饮食（R）组，限制饮食组为热量限制20%的饮食。监测大鼠母鼠的体重增加和热量摄入，并评估出生结局。测量后代下丘脑、海马体和嗅球中的2-AG、AA和NAE水平。R组母鼠从妊娠中期开始体重增加较低，且在整个孕期摄入的热量较少。R组母鼠的后代出生时体重不足，但窝仔数不受影响。在下丘脑中，R组雄性后代的AA和OEA水平降低，内源性大麻素2-AG和AEA水平无变化。R组雌性后代的2-AG和PEA水平降低。在海马体中则相反，R组雄性后代的2-AG和AA水平升高，R组雌性后代的AEA、AA和PEA水平升高。在嗅球中，只有R组雌性后代的AEA、AA和PEA水平降低。因此，整个孕期适度的饮食限制会不同程度地改变体重不足后代下丘脑和海马体中的内源性大麻素和/或内源性大麻素相关脂质，两性情况相似，而在嗅球中会出现性别特异性改变。因此，内源性大麻素和内源性大麻素相关脂质信号改变可能与营养不足和低出生体重后常见的长期和性别二态性效应有关。
