Department of Biomedical Science, West Virginia School of Osteopathic Medicine, Lewisburg, WV, USA; Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY, USA.
Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY, USA; College of Agriculture and Food Sciences, Florida Agricultural and Mechanical University, Tallahassee, FL, USA.
Domest Anim Endocrinol. 2021 Jul;76:106628. doi: 10.1016/j.domaniend.2021.106628. Epub 2021 Mar 27.
Accumulating evidence suggests that indications of metabolic syndrome can be inherited through the germline as a result of maternal obesity. We hypothesized that diet-induced maternal obesity during gestation would program metabolic consequences for multiple generations of offspring, even when first, second, and third generation offspring (F1, F2, F3, respectively) were fed only to requirements. Control (CON) and obese (OB) ewes (generation 0; F0) were bred to a single ram to produce the first generation of offspring (F1). From 60 d prior to conception through term, CONF0 ate 100% National Research Council recommendations (NRC), while OBF0 ewes ate 150% NRC. All F1, F2, and F3 ate 100% NRC after weaning. All mature F1 ewes were bred to a single ram to generate CONF2 (n = 6) and OBF2 (n = 10). All mature F2 ewes were bred to a single ram to produce CONF3 (n = 6) and OBF3 (n = 10). OBF2 ewes exhibited greater (P < 0.0001) plasma cortisol than CONF2 throughout gestation. A glucose tolerance test at 90% gestation revealed OBF2 ewes had higher (P < 0.05) insulin response with similar glucose, resulting in greater (P < 0.05) insulin resistance. OBF3 neonates had similar weight, lean mass, and body fat mass to CONF3 neonates. These data suggest that multigenerational programming of adverse metabolic phenotypes occur in association with F0 maternal obesity, yet adiposity may return to CON levels in F3 neonates.
越来越多的证据表明，由于母体肥胖，代谢综合征的迹象可以通过种系遗传。我们假设，在妊娠期间诱导母体肥胖会为后代的多代产生代谢后果，即使第一代、第二代和第三代后代（分别为 F1、F2 和 F3）仅根据需求喂养。对照（CON）和肥胖（OB）母羊（第 0 代；F0）与一只公羊交配以产生第一代后代（F1）。从受孕前 60 天到分娩时，CONF0 吃了 100%的国家研究委员会建议（NRC），而 OBF0 母羊吃了 150%的 NRC。所有 F1、F2 和 F3 在断奶后吃 100%的 NRC。所有成熟的 F1 母羊与一只公羊交配，以产生 CONF2（n=6）和 OBF2（n=10）。所有成熟的 F2 母羊与一只公羊交配，以产生 CONF3（n=6）和 OBF3（n=10）。OBF2 母羊在整个妊娠期间的血浆皮质醇水平高于 CONF2（P < 0.0001）。在妊娠 90%时进行葡萄糖耐量试验显示，OBF2 母羊的胰岛素反应更高（P < 0.05），但葡萄糖水平相似，导致胰岛素抵抗更高（P < 0.05）。OBF3 新生儿的体重、瘦体重和体脂肪量与 CONF3 新生儿相似。这些数据表明，与 F0 母体肥胖相关，不良代谢表型的多代编程发生，但肥胖可能会在 F3 新生儿中恢复到 CON 水平。
