Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding - Implications for energy homeostasis and neuroendocrine function
Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding - Implications for energy homeostasis and neuroendocrine function
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DOI：
10.1172/jci1176
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发表时间：
1998-03-01
影响因子：
15.9
通讯作者：
Flier, JS
中科院分区：
文献类型：
--
作者：
Ahima, RS;Prabakaran, D;Flier, JS
瘦素被认为通过影响食物摄入和产热来调节能量平衡。此外，瘦素可作为神经内分泌对饥饿的反应的介质，并可调节应激反应和青春期的时间，瘦素在发育中的作用是由遗传性瘦素缺乏的ob/ob小鼠的神经内分泌和结构神经元异常的存在而提出的。在这里，我们试图确定瘦素表达的个体发育及其与神经内分泌轴的关系。雌性小鼠在出生后第二周的独立csf脂肪量增加5-10倍，断奶后下降。瘦素的增加先于成年皮质酮、甲状腺素和雌二醇水平的建立。与成年小鼠相反，瘦素在出生后早期不受食物剥夺的急性调节，瘦素、皮质酮、和甲状腺素受成年小鼠摄食量的调节。当自由采食限制在光周期，皮质酮水平的峰值转移到光周期的开始，正好与瘦素的最低点。瘦素和皮质酮之间的负相关关系保持这样的瘦素喂养后的上升与皮质酮的下降。为了确定在食物限制期间皮质酮的变化是否是由瘦素介导的，我们比较了ob/ob、db/db和瘦小鼠的皮质酮水平模式。尽管ob/ob小鼠的皮质酮基础水平较高，但瘦素缺乏并不能阻止皮质酮的夜间升高。与此相反，db/db小鼠皮质酮的夜间高峰减弱。因此，除瘦素外，其他因素可能也参与了皮质酮昼夜节律的调节。新生和成年小鼠瘦素与其他激素的时间关系表明，瘦素参与了神经内分泌轴的成熟和功能。
Leptin is thought to regulate energy balance through effects on food intake and thermogenesis. In addition, leptin may serve as a mediator of the neuroendocrine response to starvation, and may modulate the stress response and the timing of puberty, A role for leptin in development is suggested by the presence of neuroendocrine and structural neuronal abnormalities in ob/ob mice with genetic leptin deficiency. Here, we sought to determine the ontogeny of leptin expression and its relationship to the developing neuroendocrine axis. Leptin increased 5-10-fold in female mice during the second postnatal week independent csf fat mass, and declined after weaning, The rise in leptin preceded the establishment of adult levels of corticosterone, thyroxine, and estradiol, In contrast to adult mice, leptin was not acutely regulated by food deprivation during the early postnatal period, Circadian rhythms of leptin, corticosterone, and thyroxine were regulated by food intake in adult mice. When ad libitum feeding was restricted to the light cycle, peak corticosterone levels were shifted to the beginning of the light cycle and coincided with the nadir of leptin. The inverse relationship between leptin and corticosterone was maintained such that a rise in leptin after feeding was associated with a decline in corticosterone. To determine whether changes in corticosterone during food restriction are mediated by leptin, we compared the patterns of corticosterone levels among ob/ob, db/db and lean mice, Despite their higher basal levels of corticosterone, Ieptin deficiency in ob/ob mice did not prevent the nocturnal rise in corticosterone. In contrast, the nocturnal surge of corticosterone was blunted in db/db mice, Therefore, it is likely that factors in addition to leptin are involved in the regulation of the circadian rhythm of corticosterone, The temporal relationship between leptin and other hormones in neonatal and adult mice suggests that leptin is involved in the maturation and function of the neuroendocrine axis.