Psychology Department, Bar Ilan University, Ramat Gan, Israel.
PLoS One. 2010 Nov 3;5(11):e13825. doi: 10.1371/journal.pone.0013825.
The OLETF rat is an animal model of early onset hyperphagia induced obesity, presenting multiple pre-obese characteristics during the suckling period. In the present study, we used a cross-fostering strategy to assess whether interactions with obese dams in the postnatal environment contributed to the development of obesity.
On postnatal Day (PND)-1 OLETF and control LETO pups were cross-fostered to same or opposite strain dams. An independent ingestion test was performed on PND11 and a nursing test on PND18. Rats were sacrificed at weaning or on PND90, and plasma leptin, insulin, cholesterol, triglycerides and alanine aminotransferase (ALT) were assayed. Fat pads were collected and weighed and adipocyte size and number were estimated. Body weight and intake, as well as the estrous cycle of the female offspring were monitored.
During the suckling period, the pups' phenotype was almost completely determined by the strain of the mother. However, pups independently ingested food according to their genotype, regardless of their actual phenotype. At adulthood, cross fostered males of both strains and LETO females were affected in regard of their adiposity levels in the direction of the foster dam. On the other hand, OLETF females showed almost no alterations in adiposity but were affected by the strain of the dams in parameters related to the metabolic syndrome. Thus, OLETF females showed reduced liver adiposity and circulating levels of ALT, while LETO females presented a disrupted estrous cycle and increased cholesterol and triglycerides in the long term.
The present study provides further support for the early postnatal environment playing a sex-divergent role in programming later life phenotype. In addition, it plays a more central role in determining the functioning of mechanisms involved in energy balance that may provide protection from or sensitivity to later life obesity and pathologies related to the metabolic syndrome.
OLETF 大鼠是一种早期发生的摄食过度诱导肥胖的动物模型，在哺乳期表现出多种肥胖前特征。在本研究中，我们使用了交叉寄养策略来评估产后环境中与肥胖母鼠的相互作用是否有助于肥胖的发展。
在出生后第 1 天（PND），将 OLETF 和对照 LETO 幼鼠交叉寄养给相同或相反品系的母鼠。在 PND11 进行独立摄食测试，在 PND18 进行哺乳测试。在断奶或 PND90 时处死大鼠，测定血浆瘦素、胰岛素、胆固醇、甘油三酯和丙氨酸氨基转移酶（ALT）。收集脂肪垫并称重，估算脂肪细胞大小和数量。监测雌性后代的体重和摄食量以及发情周期。
在哺乳期，幼鼠的表型几乎完全由母鼠的品系决定。然而，幼鼠根据其基因型独立进食，而不管其实际表型如何。在成年期，两种品系的寄养雄性和 LETO 雌性的肥胖程度都朝着寄养母鼠的方向受到影响。另一方面，OLETF 雌性的肥胖程度几乎没有改变，但受母鼠品系的影响，与代谢综合征相关的参数发生了改变。因此，OLETF 雌性的肝脏脂肪和循环 ALT 水平降低，而 LETO 雌性的发情周期紊乱，胆固醇和甘油三酯水平升高。
本研究进一步支持了早期产后环境在编程后期生命表型方面发挥性别差异作用。此外，它在决定参与能量平衡的机制的功能方面发挥了更核心的作用，这些机制可能提供对后期肥胖和代谢综合征相关病理的保护或敏感性。
