Maternal obesity eliminates the neonatal lamb plasma leptin peak
Maternal obesity eliminates the neonatal lamb plasma leptin peak
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DOI：
10.1113/jphysiol.2010.201681
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发表时间：
2011-03-15
影响因子：
5.5
通讯作者：
Nathanielsz, Peter W.
中科院分区：
文献类型：
--
作者：
Long, Nathan M.;Ford, Stephen P.;Nathanielsz, Peter W.
非技术概述瘦素，一种脂肪组织激素，抑制大脑的中枢进食驱动力，使正常的体重和组成得以维持。新生啮齿类动物中存在的瘦素峰控制着大脑食欲调节区的发育，其时间和幅度的改变易导致以后的肥胖。然而，与人类不同，啮齿动物出生在发育的不成熟阶段，因此为了确定与人类发育的潜在相关性，我们检查了新生羔羊中的瘦素峰，这些羔羊出生在与人类相当的更高级成熟水平。正常峰值是不存在的羔羊出生的肥胖母亲谁表现出较高的新生儿血浆皮质醇水平。我们的结论是，存在的相似性和差异，新生儿瘦素的物种出生不成熟或成熟。这一信息有助于了解妇女肥胖流行对其后代的影响，并将有助于促进诊断、预防和治疗。啮齿动物血浆瘦素的新生儿峰值在调节下丘脑食欲控制中心的发育中起着核心作用。母体肥胖延长并放大了晚期啮齿动物物种的峰值。新生儿瘦素峰值的精确时间和特征尚未在任何早熟物种的正常或肥胖母亲的后代中建立。我们诱导肥胖喂养雌性绵羊60天前受孕，并在整个怀孕和分娩的控制母羊喂养国家研究理事会的建议消耗的饮食的150%。我们已经报道过，在19月龄时，以类似方式喂养的肥胖绵羊的成熟后代表现出对自由采食的反应，食欲增加，体重增加和肥胖。我们观察到的瘦素峰值之间的第6和第9天的出生后的生活，早于在啮齿动物中报道的控制母羊的羔羊。这一峰值不存在于羔羊出生的肥胖母羊。出生控制母羊的羔羊瘦素峰值没有明显相关的血浆皮质醇，胰岛素，三碘甲腺原氨酸，IGF-1或葡萄糖的任何变化。然而，有一个显着增加皮质醇在出生的羔羊出生肥胖母羊有关的瘦素增加，在第一天的生活。我们的结论是，增加皮质醇看到在羔羊肥胖绵羊发挥了作用，在破坏正常的瘦素峰值出生的羔羊肥胖母羊，从而使他们在以后的生活中增加食欲和体重增加。
Non technical summaryLeptin, an adipose tissue hormone, inhibits the brain's central drive to eat, enabling maintenance of normal body weight and composition. The leptin peak present in newborn rodents controls development of brain appetite regulatory areas, and alteration in its timing and amplitude predisposes to obesity in later life. However, unlike humans, rodents are born at an immature stage of development so to determine potential relevance to human development, we examined the leptin peak in newborn lambs, born at a more advanced level of maturity equivalent to humans. The normal peak was absent in lambs born to obese mothers who showed higher newborn levels of plasma cortisol. We conclude that similarities and differences exist in neonatal leptin in species born immature or mature. This information aids understanding of effects of the obesity epidemic in women on their offspring and will help promote diagnosis, prevention and therapy.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.