Postnatal regulation of hypothalamic neuropeptide expression by leptin: implications for energy balance and body weight regulation
Postnatal regulation of hypothalamic neuropeptide expression by leptin: implications for energy balance and body weight regulation
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DOI：
10.1016/s0167-0115(00)00142-7
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发表时间：
2000-08-25
影响因子：
--
通讯作者：
Hileman, SM
中科院分区：
文献类型：
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作者：
Ahima, RS;Hileman, SM
瘦素主要由脂肪组织产生，并已被证明可调节摄食、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是由下丘脑神经肽介导的，至少在成年啮齿动物中是这样。新生儿期是发育的关键阶段，在此期间，哺乳动物必须优化热量摄入以支持生长和发育，以及维持体温。瘦素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，我们比较了瘦素治疗对新生和成年小鼠体重和肥胖的影响。我们还确定了是否众所周知的下丘脑神经肽靶点，如神经肽Y（NPY），阿黑皮素原（POMC），刺豚鼠相关肽（AGRP）和可卡因和安非他明调节的转录本（CART）的调节模式与其作为瘦素作用介质的假定作用一致。每天一次腹腔注射瘦素7天没有改变体重，脂肪含量或下丘脑神经肽mRNA的表达在10日龄小鼠。与此相反，瘦素降低体重和肥胖，增加CART和抑制NPY和AGRP mRNA表达的成年小鼠。这些结果与先前的研究一致，表明瘦素的厌食作用的时间是在断奶后发展的。此外，瘦素的能力，影响体重在成年小鼠，但不是在新生儿，和下丘脑神经肽mRNA表达的调节之间的关联，是一致的，认为这些肽介导瘦素的影响能量平衡。(C)2000 Elsevier Science B.V.保留所有权利。
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. (C) 2000 Elsevier Science B.V. All rights reserved.