Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues
Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues
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DOI：
10.1073/pnas.94.13.7001
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发表时间：
1997-06-24
影响因子：
11.1
通讯作者：
Friedman, JM
中科院分区：
文献类型：
--
作者：
Fei, H;Okano, HJ;Friedman, JM
瘦素的作用是通过与选择性剪接的受体相互作用介导的，导致至少五种不同的小鼠形式：Ob-Ra、Ob-Rb、Ob-Rc、Ob-Rd和Ob-Re，一种剪接形式Ob-Rb中的突变导致小鼠肥胖，北方印迹、RNA酶保护测定和PCR表明Ob-Rb在下丘脑中以相对高的水平表达，而在几种其他组织中以低的水平表达，Ob-Ra普遍表达，而Ob-Rc、-Rd和-Re RNA仅可使用PCR检测。在下丘脑中，Ob-Rb存在于弓状核、腹内侧核、背内侧核和外侧下丘脑核中，但在其他脑区域中不可检测。已知这些核调节食物摄入和体重。金硫葡萄糖（gold thioglucose，GTG）致肥胖小鼠下丘脑中Ob-Rb水平降低，导致下丘脑病变。GTG治疗小鼠的肥胖可能是由Ob-Rb表达神经元的消融导致瘦素抵抗所致。
Leptin's effects are mediated by interactions with a receptor that is alternatively spliced, resulting in at least five different murine forms: Ob-Ra, Ob-Rb, Ob-Rc, Ob-Rd, and Ob-Re, A mutation in one splice form, Ob-Rb, results in obesity in mice, Northern blots, RNase protection assays, and PCR indicate that Ob-Rb is expressed at a relatively high level in hypothalamus and low level in several other tissues, Ob-Ra is expressed ubiquitously, whereas Ob-Rc, -Rd, and -Re RNAs are only detectable using PCR, In hypothalamus, Ob-Rb is present in the arcuate, ventromedial, dorsomedial, and lateral hypothalamic nuclei but is not detectable in other brain regions, These nuclei are known to regulate food intake and body weight. The level of Ob-Rb in hypothalamus is reduced in mice rendered obese by gold thioglucose (GTG), which causes hypothalamic lesions, The obesity in GTG treated mice is likely to be caused by ablation of Ob-Rb-expressing neurons, which results in leptin resistance.