Ahima R S, Prabakaran D, Flier J S
Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
J Clin Invest. 1998 Mar 1;101(5):1020-7. doi: 10.1172/JCI1176.
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 of 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, leptin 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.
瘦素被认为通过对食物摄入和产热的影响来调节能量平衡。此外，瘦素可能作为对饥饿的神经内分泌反应的介质，并可能调节应激反应和青春期的时间。遗传性瘦素缺乏的ob/ob小鼠中存在神经内分泌和结构性神经元异常，提示瘦素在发育过程中发挥作用。在此，我们试图确定瘦素表达的个体发生及其与发育中的神经内分泌轴的关系。雌性小鼠在出生后第二周瘦素增加了5至10倍，与脂肪量无关，断奶后下降。瘦素的升高先于成年水平的皮质酮、甲状腺素和雌二醇的建立。与成年小鼠不同，出生后早期瘦素不受食物剥夺的急性调节。成年小鼠中瘦素、皮质酮和甲状腺素的昼夜节律受食物摄入调节。当随意进食仅限于光照周期时，皮质酮峰值水平转移到光照周期开始时，并与瘦素的最低点一致。瘦素与皮质酮之间的反向关系得以维持，即进食后瘦素升高与皮质酮下降相关。为了确定食物限制期间皮质酮的变化是否由瘦素介导，我们比较了ob/ob、db/db和瘦小鼠中皮质酮水平的模式。尽管ob/ob小鼠的皮质酮基础水平较高，但瘦素缺乏并未阻止皮质酮的夜间升高。相反，db/db小鼠中皮质酮的夜间激增减弱。因此，除瘦素外的其他因素可能参与了皮质酮昼夜节律的调节。新生小鼠和成年小鼠中瘦素与其他激素之间的时间关系表明，瘦素参与了神经内分泌轴的成熟和功能。
