Rodríguez-Rodríguez Pilar, Monedero-Cobeta Ignacio, Ramiro-Cortijo David, Puthong Sophida, Quintana-Villamandos Begoña, Gil-Ramírez Alicia, Cañas Silvia, Ruvira Santiago, Arribas Silvia M
Department of Physiology, Faculty of Medicine, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Food, Oxidative Stress and Cardiovascular Health (FOSCH) Research Group, Universidad Autónoma de Madrid, Ciudad Universitaria de Cantoblanco, 28049 Madrid, Spain.
Biomedicines. 2022 Oct 7;10(10):2504. doi: 10.3390/biomedicines10102504.
Low birth weight (LBW) and accelerated growth during lactation are associated with cardiometabolic disease development. LBW offspring from rats exposed to undernutrition during gestation (MUN) develops hypertension. In this rat model, we tested if slower postnatal growth improves early cardiometabolic alterations. MUN dams were fed during gestation days 1-10, with 50% of the daily intake during days 11-21 and during lactation. Control dams were always fed Pups were maintained with their own mother or cross-fostered. Body weight and length were recorded weekly, and breastmilk was obtained. At weaning, the heart was evaluated by echocardiography, and aorta structure and adipocytes in white perivascular fat were studied by confocal microscopy (size, % beige-adipocytes by Mitotracker staining). Breastmilk protein and fat content were not significantly different between groups. Compared to controls, MUN males significantly accelerated body weight gain during the exclusive lactation period (days 1-14) while females accelerated during the last week; length growth was slower in MUN rats from both sexes. By weaning, MUN males, but not females, showed reduced diastolic function and hypertrophy in the heart, aorta, and adipocytes; the percentage of beige-type adipocytes was smaller in MUN males and females. Fostering MUN offspring on control dams significantly reduced weight gain rate, cardiovascular, and fat hypertrophy, increasing beige-adipocyte proportion. Control offspring nursed by MUN mothers reduced body growth gain, without cardiovascular modifications. In conclusion, slower growth during lactation can rescue early cardiovascular alterations induced by fetal undernutrition. Exclusive lactation was a key period, despite no modifications in breastmilk macronutrients, suggesting the role of bioactive components. Our data support that lactation is a key period to counteract cardiometabolic disease programming in LBW and a potential intervention window for the mother.
低出生体重（LBW）和哺乳期生长加速与心脏代谢疾病的发生有关。孕期暴露于营养不足（MUN）的大鼠所产低出生体重后代会发生高血压。在这个大鼠模型中，我们测试了出生后生长较慢是否能改善早期心脏代谢改变。MUN母鼠在妊娠第1 - 10天给予50%日常摄入量的食物，第11 - 21天以及哺乳期给予正常量50%的食物。对照母鼠始终给予正常量食物。幼崽由自己的母亲抚养或进行交叉寄养。每周记录体重和体长，并采集母乳。断奶时，通过超声心动图评估心脏，通过共聚焦显微镜研究主动脉结构和血管周围白色脂肪中的脂肪细胞（大小、通过线粒体追踪染料染色评估米色脂肪细胞百分比）。两组之间母乳的蛋白质和脂肪含量无显著差异。与对照组相比，MUN雄性在纯哺乳期（第1 - 14天）体重显著加速增加，而雌性在最后一周加速增加；两性的MUN大鼠体长生长较慢。到断奶时，MUN雄性而非雌性在心脏、主动脉和脂肪细胞中表现出舒张功能降低和肥大；MUN雄性和雌性的米色型脂肪细胞百分比均较小。将MUN后代寄养在对照母鼠上可显著降低体重增加率、心血管和脂肪肥大，增加米色脂肪细胞比例。由MUN母亲哺育的对照后代身体生长增加减缓，但无心血管改变。总之，哺乳期生长较慢可挽救胎儿营养不足引起的早期心血管改变。尽管母乳中的常量营养素没有变化，但纯哺乳期是一个关键时期，提示生物活性成分的作用。我们的数据支持哺乳期是对抗低出生体重儿心脏代谢疾病编程的关键时期，也是母亲潜在的干预窗口。
