Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice
Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice
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DOI：
10.2337/diabetes.45.4.531
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发表时间：
1996-04-01
期刊：
影响因子：
7.7
通讯作者：
Weigle, DS
中科院分区：
文献类型：
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作者：
Schwartz, MW;Baskin, DG;Weigle, DS
纠正遗传性瘦素缺乏引起的肥胖状态可降低ob/ob小鼠血糖和下丘脑神经肽Y（NPY）mRNA水平的升高。为了确定这些反应是否是由于瘦素的特定作用或肥胖状态的逆转，我们研究了全身性瘦素给药对ob/ob小鼠（n = 8）血浆葡萄糖和胰岛素水平以及下丘脑NPY mRNA表达的We效应的特异性。生理盐水处理的对照组自由进食（n = 8）或成对进食瘦素处理组（n = 8）的摄入量，以控制瘦素诱导的食物摄入量的变化。通过1）测量对瘦素有抗性的db/db小鼠（n = 6）中的NPY基因表达，2）测量下丘脑外的脑区域中的NPY基因表达，和3）测量瘦素施用对下丘脑促肾上腺皮质激素释放激素（CRH）mRNA表达的影响，进一步评估瘦素作用的特异性。与生理盐水对照组相比，ob/ob小鼠腹腔注射重组小鼠瘦素（150 μ g）5次，摄食量降低56%（P <0.05），体重降低4.1%（P < 0.05），下丘脑弓状核NPY mRNA水平降低42.3%（P < 0.05）。成对喂养ob/ob小鼠摄入瘦素治疗的动物产生同等的体重减轻，但没有改变弓状核中NPY mRNA的表达。瘦素给药对db/db小鼠的摄食量、体重或弓状核中的NPY mRNA水平也没有影响。在ob/ob小鼠中，瘦素不改变大脑皮质或海马中的NPY mRNA水平或下丘脑室旁核（PVN）中CRH mRNA的表达。肥胖基因型小鼠给予瘦素也能显著降低血清葡萄糖（8.3 +/- 1.2 vs，24.5 +/- 3.8 mmol/l; P < 0.01）和胰岛素水平（7，263 +/-1，309 vs. 3，150 +/- 780 pmol/l），但对db/db小鼠无效。配对喂养的小鼠经历了葡萄糖和胰岛素水平的降低，
Correction of the obese state induced by genetic leptin deficiency reduces elevated levels of both blood glucose and hypothalamic neuropeptide Y (NPY) mRNA in ob/ob mice. To determine whether these responses are due to a specific action of leptin or to the reversal of the obese state, we investigated the specificity of We effect of systemic leptin administration to ob/ob mice (n = 8) on levels of plasma glucose and insulin and on hypothalamic expression of NPY mRNA. Saline-treated controls were either fed ad libitum (n = 8) or pair-fed to the intake of the leptin-treated group (n = 8) to control for changes of food intake induced by leptin. The specificity of the effect of leptin was further assessed by 1) measuring NPY gene expression in db/db mice (n = 6) that are resistant to leptin, 2) measuring NPY gene expression in brain areas outside the hypothalamus, and 3) measuring the effect of leptin administration on hypothalamic expression of corticotropin-releasing hormone (CRH) mRNA. Five daily intraperitoneal injections of recombinant mouse leptin (150 mu g) in ob/ob mice lowered food intake by 56% (P < 0.05), body weight by 4.1% (P < 0.05), and levels of NPY mRNA in the hypothalamic arcuate nucleus by 42.3% (P < 0.05) as compared with saline-treated controls. Pair-feeding of ob/ob mice to the intake of leptin-treated animals produced equivalent weight loss, but did not alter expression of NPY mRNA in the arcuate nucleus. Leptin administration was also without effect on food intake, body weight, or NPY mRNA levels in the arcuate nucleus of db/db mice, in ob/ob mice, leptin did not alter NPY mRNA levels in cerebral cortex or hippocampus or the expression of CRH mRNA in the hypothalamic paraventricular nucleus (PVN). Leptin administration to ob/ob mice also markedly reduced serum glucose (8.3 +/- 1.2 vs, 24.5 +/- 3.8 mmol/l; P < 0.01) and insulin levels (7,263 +/-1,309 vs. 3,150 +/- 780 pmol/l), but was ineffective in db/db mice. Pair-fed mice experienced reductions of glucose and insulin levels that were