Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus
Leptin receptor mRNA identifies a subpopulation of neuropeptide Y neurons activated by fasting in rat hypothalamus
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DOI：
10.2337/diabetes.48.4.828
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发表时间：
1999-04-01
期刊：
影响因子：
7.7
通讯作者：
Schwartz, MW
中科院分区：
文献类型：
--
作者：
Baskin, DG;Breininger, JF;Schwartz, MW
禁食期间瘦素(Ob蛋白)浓度的下降是下丘脑促食欲素多肽神经肽Y(NPY)表达增加的信号。为了验证摄食对弓状核NPY激活的影响是由Leptin介导的假说，我们同时进行了三重原位杂交共定位研究，以确定禁食激活的NPY神经元亚群是否优先表达Leptin受体(Ob-Rb)的长型，从而用荧光原位杂交、原位杂交和同位素原位杂交相结合的方法在喂养和禁食大鼠的弓状核共定位编码NPY和前阿片黑素皮质素(POMC)的mRNAs在喂养的动物中，47%的含有NPY mRNA的弓状核神经元也含有Ob-Rb mRNA，而在POMC神经元中，这一比例为79%(P<；禁食2天后，含NPY mRNA的弓状核神经元数目增加50%(P=0.013)，共表达Ob-Rb的弓状核神经元数目增加2倍(P=0.02)，单个NPY神经元的Ob-Rb mRNA杂交量增加0.02%(P<；0.02)，而共表达Ob-Rb的POMC神经元数目无明显变化。对这些发现的一个重要解释是，不表达可检测到的Ob-Rb mRNA的NPY神经元不会被禁食激活，而由禁食激活的NPY神经元是表达Ob-Rb的神经元，这些数据表明表达Ob-Rb的NPY神经元与不表达Ob-Rb的NPY神经元之间存在显著的生理差异。这些结果支持了食物摄入对NPY神经元的影响是通过这些NPY细胞表达的Ob-Rb受体直接作用于瘦素的结论。结果还表明，Ob-Rb的表达是弓状核NPY神经元亚群的一个决定性的表型特征，这些神经元被禁食激活，并在对负能量平衡的适应性反应中发挥核心作用。
The decline of leptin (Ob protein) concentrations during fasting is implicated as a signal for increasing the expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamus, To test the hypothesis that the effects of food intake on arcuate nucleus NPY activation are mediated by leptin, we performed simultaneous triple in situ hybridization colocalization studies to determine whether the subset of NPY neurons that are activated by fasting preferentially expresses the long form of the leptin receptor (Ob-Rb), Thus, mRNAs encoding NPY and pro-opiomelanocortin (POMC) were colocalized in the arcuate nucleus of fed and fasted rats by fluorescence in situ hybridization in combination,vith isotopic in situ hybridization for Ob-Rb mRNA, In fed animals, 47% of arcuate nucleus neurons containing NPY mRNA also contained Ob-Rb mRNA, compared with 79% of POMC neurons (P < 0.01), After a 2-day fast, the number of arcuate nucleus neurons with NPY mRNA increased 50% (P < 0.05); the number of these that coexpressed Ob-Rb increased twofold (P = 0.013), Furthermore, Ob-Rb mRNA hybridization in individual NPY neurons increased by 64% (P < 0.02), In contrast, the number of POMC neurons that coexpressed Ob-Rb was unchanged. A significant interpretation of these findings is that the NPY neurons that do not express detectable levels of Ob-Rb mRNA are not activated by fasting, whereas the NPY neurons that are activated by fasting are the ones that express Ob-Rb, These data demonstrate a significant physiological difference between NPY neurons that express Ob-Rb and those that do not. The results support the conclusion that the effect of food intake on NPY neurons is mediated by the direct action of leptin via Ob-Rb receptors expressed by these NPY cells. The results also indicate that expression of Ob-Rb is a defining phenotypic characteristic of the subset of arcuate nucleus NPY neurons that are activated by fasting and play a central role in the adaptive response to negative energy balance.