Ahima R S, Hileman S M
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, 764 Clinical Research Building, 415 Curie Blvd., 19104, Philadelphia, PA, USA.
Regul Pept. 2000 Aug 25;92(1-3):1-7. doi: 10.1016/s0167-0115(00)00142-7.
Leptin is produced mainly by adipose tissue and has been shown to regulate feeding, energy balance and neuroendocrine function. Regulation of energy homeostasis by leptin is thought to be mediated by hypothalamic neuropeptides, at least in adult rodents. The neonatal period is a critical stage of development during which mammals have to optimize caloric intake to support growth and development, as well as maintain body temperature. It is likely that leptin is involved in the transition from preweaning to adult metabolism. To test this hypothesis, we compared the effect of leptin treatment on body weight and adiposity between neonatal and adult mice. We also determined whether well known hypothalamic neuropeptide targets, e.g. neuropeptide Y (NPY), proopiomelanocortin (POMC), agouti-related peptide (AGRP) and cocaine and amphetamine-regulated transcript (CART) were regulated in a pattern consistent with their presumed roles as mediators of leptin action. Once daily intraperitoneal leptin injection for 7 days did not alter body weight, fat content or expression of hypothalamic neuropeptide mRNAs in 10-day-old mice. In contrast, leptin decreased body weight and adiposity, increased CART and suppressed NPY and AGRP mRNA expression in adult mice. These results are consistent with previous studies showing that the timing of leptin's anorectic action develops after weaning. Furthermore, the association between leptin's ability to influence body weight in adult mice but not in neonates, and the regulation of hypothalamic neuropeptide mRNA expression, is consistent with the view that these peptides mediate leptin's effects on energy balance.
瘦素主要由脂肪组织产生，并且已被证明可调节进食、能量平衡和神经内分泌功能。瘦素对能量稳态的调节被认为至少在成年啮齿动物中是由下丘脑神经肽介导的。新生儿期是一个关键的发育阶段，在此期间哺乳动物必须优化热量摄入以支持生长发育以及维持体温。瘦素很可能参与了从断奶前到成年代谢的转变。为了验证这一假设，我们比较了瘦素处理对新生小鼠和成年小鼠体重及肥胖程度的影响。我们还确定了下丘脑神经肽的一些已知靶点，例如神经肽Y（NPY）、阿黑皮素原（POMC）、刺鼠相关肽（AGRP）以及可卡因和苯丙胺调节转录物（CART）是否按照与其作为瘦素作用介质的假定作用相一致的模式受到调节。对10日龄小鼠每天腹腔注射一次瘦素，持续7天，并未改变其体重、脂肪含量或下丘脑神经肽mRNA的表达。相比之下，瘦素可降低成年小鼠的体重和肥胖程度，增加CART表达，并抑制NPY和AGRP mRNA的表达。这些结果与之前的研究一致，即瘦素的厌食作用在断奶后才出现。此外，瘦素影响成年小鼠而非新生小鼠体重的能力与下丘脑神经肽mRNA表达的调节之间的关联，与这些肽介导瘦素对能量平衡的影响这一观点相符。
