Wattez J-S, Delahaye F, Barella L F, Dickes-Coopman A, Montel V, Breton C, Mathias P, Foligné B, Lesage J, Vieau D
1 Environnement Périnatal et Croissance (EA4489), Université Lille-Nord de France, Equipe Dénutritions Maternelles Périnatales, SN4, Université de Lille 1, Villeneuve d'Ascq, France.
3 Department of Cell Biology and Genetics, Laboratory of Secretion Cell Biology, State University of Maringá, Brazil.
J Dev Orig Health Dis. 2014 Apr;5(2):109-20. doi: 10.1017/S2040174413000548.
Undernutrition exposure during the perinatal period reduces the growth kinetic of the offspring and sensitizes it to the development of chronic adult metabolic diseases both in animals and in humans. Previous studies have demonstrated that a 50% maternal food restriction performed during the last week of gestation and during lactation has both short- and long-term consequences in the male rat offspring. Pups from undernourished mothers present a decreased intrauterine (IUGR) and extrauterine growth restriction. This is associated with a drastic reduction in their leptin plasma levels during lactation, and exhibit programming of their stress neuroendocrine systems (corticotroph axis and sympatho-adrenal system) in adulthood. In this study, we report that perinatally undernourished 6-month-old adult animals demonstrated increased leptinemia (at PND200), blood pressure (at PND180), food intake (from PND28 to PND168), locomotor activity (PND187) and altered regulation of glycemia (PND193). Cross-fostering experiments indicate that these alterations were prevented in IUGR offspring nursed by control mothers during lactation. Interestingly, the nutritional status of mothers during lactation (ad libitum feeding v. undernutrition) dictates the leptin plasma levels in pups, consistent with decreased leptin concentration in the milk of mothers subjected to perinatal undernutrition. As it has been reported that postnatal leptin levels in rodent neonates may have long-term metabolic consequences, restoration of plasma leptin levels in pups during lactation may contribute to the beneficial effects of cross-fostering IUGR offspring to control mothers. Collectively, our data suggest that modification of milk components may offer new therapeutic perspectives to prevent the programming of adult diseases in offspring from perinatally undernourished mothers.
围产期营养不良会降低后代的生长动力学，并使其对成年慢性代谢性疾病的发展敏感，这在动物和人类中均如此。先前的研究表明，在妊娠最后一周和哺乳期进行50%的母体食物限制对雄性大鼠后代有短期和长期影响。营养不良母亲的幼崽表现出宫内（IUGR）和宫外生长受限。这与哺乳期其血浆瘦素水平的急剧降低有关，并在成年期表现出应激神经内分泌系统（促肾上腺皮质激素轴和交感-肾上腺系统）的程序化。在本研究中，我们报告围产期营养不良的6个月大成年动物表现出瘦素血症增加（在PND200时）、血压升高（在PND180时）、食物摄入量增加（从PND28到PND168）、运动活动增加（PND187）以及血糖调节改变（PND193）。交叉寄养实验表明，哺乳期由对照母亲哺育的IUGR后代可预防这些改变。有趣的是，哺乳期母亲的营养状况（自由进食与营养不良）决定了幼崽的血浆瘦素水平，这与围产期营养不良母亲乳汁中瘦素浓度降低一致。正如所报道的，啮齿动物新生儿出生后的瘦素水平可能具有长期代谢后果，哺乳期幼崽血浆瘦素水平的恢复可能有助于将IUGR后代交叉寄养给对照母亲的有益效果。总体而言，我们的数据表明，改变乳汁成分可能为预防围产期营养不良母亲后代成年疾病的程序化提供新的治疗前景。
