Center for Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY, USA.
J Physiol. 2011 Mar 15;589(Pt 6):1455-62. doi: 10.1113/jphysiol.2010.201681. Epub 2011 Jan 24.
A neonatal peak in rodent plasma leptin plays a central role in regulating development of the hypothalamic appetite control centres. Maternal obesity lengthens and amplifies the peak in altricial rodent species. The precise timing and characteristics of the neonatal leptin peak have not been established in offspring of either normal or obese mothers in any precocial species. We induced obesity by feeding female sheep for 60 days before conception, and throughout pregnancy and parturition with 150% of the diet consumed by control ewes fed to National Research Council recommendations.We have reported that mature offspring of obese sheep fed similarly exhibited increased appetite, weight gain and obesity in response to ad libitum feeding at 19 months of age. We observed a leptin peak in lambs of control ewes between days 6 and 9 of postnatal life, earlier than reported in rodents. This peak was not present in lambs born to obese ewes. The leptin peak in lambs born to control ewes was not clearly related to any changes in plasma cortisol, insulin, triiodothyronine, IGF-1 or glucose. However, there was a significant increase in cortisol at birth in lambs born to obese ewes related to an increase in leptin in the first day of life. We conclude that the increased cortisol seen in lambs of obese sheep plays a role in disrupting the normal peak of leptin in lambs born to obese ewes thereby predisposing them to increased appetite and weight gain in later life.
啮齿动物血浆瘦素的新生儿高峰在调节下丘脑食欲控制中心的发育中起核心作用。母体肥胖会延长并放大早产儿物种的瘦素高峰。在任何早熟物种中,无论是正常母亲还是肥胖母亲的后代,其新生儿瘦素高峰的精确时间和特征都尚未确定。我们通过在受孕前 60 天开始给雌性绵羊喂食,在整个怀孕期间和分娩期间喂食 150%的饮食,来诱导肥胖。我们已经报道过,接受类似喂养的肥胖绵羊的成熟后代在 19 个月大时表现出增加的食欲、体重增加和肥胖,这是对自由进食的反应。我们观察到对照组母羊的羔羊在产后第 6 至 9 天之间出现瘦素高峰,这比在啮齿动物中报道的更早。而在肥胖母羊所生的羔羊中则没有出现这种高峰。对照组母羊所生羔羊的瘦素高峰与血浆皮质醇、胰岛素、三碘甲状腺原氨酸、IGF-1 或葡萄糖的任何变化都没有明显关系。然而,肥胖母羊所生羔羊在出生时皮质醇显著增加,这与生命的第一天瘦素增加有关。我们得出结论,肥胖绵羊羔羊中所见的增加的皮质醇在破坏肥胖母羊所生羔羊正常的瘦素高峰方面发挥了作用,从而使它们在以后的生活中更容易出现食欲增加和体重增加。