Leptin regulates appetite-related neuropeptides in the hypothalamus of developing rats without affecting food intake.
Leptin regulates appetite-related neuropeptides in the hypothalamus of developing rats without affecting food intake.
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DOI：
10.1210/en.2002-220593
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发表时间：
2002-12
期刊：
影响因子：
4.8
通讯作者：
K. Proulx;D. Richard;C. Walker
中科院分区：
文献类型：
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作者：
K. Proulx;D. Richard;C. Walker
瘦素通过刺激下丘脑促食欲途径和抑制促食欲途径来调节成年哺乳动物的食物摄入。在发育中的啮齿动物中，脂肪储存量很低，但循环中的瘦素水平很高，似乎不能调节食物摄入。我们确定了两种食欲相关的神经肽[神经肽Y（NPY）和前阿黑皮素（POMC）]和食物摄入行为是否对新生儿瘦素[3 mg/kg体重（BW），ip]敏感。我们测量了1）急性瘦素施用（3 mg/kg BW，ip，测试前3小时）对出生后（PND）第5、8和10天的食物摄入的影响;和2）慢性瘦素处理（3 mg/kg BW，ip，每天PND 3-PND 10）对PND 10时的BW增加和脂肪垫重量的影响。除了下丘脑POMC和NPY表达，我们还测定了接受急性（PND 10）或慢性（PND 3 - 10）瘦素（3 mg/kg BW，ip）或溶媒治疗的PND 10幼仔中细胞因子信号传导抑制因子-3、瘦素受体所有亚型和促肾上腺皮质激素释放因子受体-2 mRNA的表达。在最后一次注射后30或120分钟取出脑。急性瘦素管理没有影响食物摄入量在任何年龄测试。长期瘦素治疗没有改变体重，但减少脂肪垫重量显着。在弓状核（ARC），急性瘦素增加SOCS-3和POMC mRNA的水平，但减少NPY mRNA的水平，在嘴部的ARC。慢性瘦素下调所有亚型的瘦素受体mRNA和减少NPY mRNA水平在尾侧ARC，但没有进一步的影响POMC的表达。慢性瘦素增加下丘脑腹内侧区促肾上腺皮质激素释放因子受体-2 mRNA水平。我们的结论是，尽管成人样的影响，瘦素对POMC，神经肽Y，和CRFR-2的表达在新生儿，瘦素不调节食物的摄入量在早期发展。
Leptin regulates food intake in adult mammals by stimulating hypothalamic anorexigenic pathways and inhibiting orexigenic ones. In developing rodents, fat stores are low, yet circulating leptin levels are high and do not appear to regulate food intake. We determined whether two appetite-related neuropeptides [neuropeptide Y (NPY) and proopiomelanocortin (POMC)] and food intake behavior are sensitive to leptin [3 mg/kg body weight (BW), ip] in neonates. We measured the effects of 1) acute leptin administration (3 mg/kg BW, ip, 3 h before testing) on food intake on postnatal day (PND) 5, 8, and 10; and 2) chronic leptin treatment (3 mg/kg BW, ip, daily PND3-PND10) on BW gain and fat pads weight on PND10. In addition to hypothalamic POMC and NPY expression, we determined the expression of suppressor of cytokine signaling-3, all subtypes of leptin receptors, and corticotropin-releasing factor receptor-2 mRNA in PND10 pups receiving either an acute (PND10) or a chronic (PND 3-10) leptin (3 mg/kg BW, ip) or vehicle treatment. Brains were removed 30 or 120 min after the last injection. Acute leptin administration did not affect food intake at any age tested. Chronic leptin treatment did not change BW but decreased fat pad weight significantly. In the arcuate nucleus (ARC), acute leptin increased SOCS-3 and POMC mRNA levels, but decreased NPY mRNA levels in the rostral part of ARC. Chronic leptin down-regulated all subtypes of leptin receptors mRNA and decreased NPY mRNA levels in the caudal ARC but had no further effect on POMC expression. Chronic leptin increased corticotropin-releasing factor receptor-2 mRNA levels in the ventromedial hypothalamus. We conclude that despite adult-like effects of leptin on POMC, NPY, and CRFR-2 expression in neonates, leptin does not regulate food intake during early development.