The hypothalamic leptin receptor in humans - Identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations
The hypothalamic leptin receptor in humans - Identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations
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DOI：
10.2337/diabetes.45.7.992
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发表时间：
1996-07-01
期刊：
影响因子：
7.7
通讯作者：
Caro, JF
中科院分区：
文献类型：
--
作者：
Considine, RV;Considine, EL;Caro, JF
瘦素受体基因在瘦人和肥胖人下丘脑组织中的表达进行了研究。全长瘦素受体被认为是传递瘦素信号的受体，在人的下丘脑中表达。通过逆转录-聚合酶链反应测定，7名瘦子（BMI 23.3 +/- 0.9 kg/m(2)）和8名肥胖者（BMI 36.9 +/- 1.5）的瘦素受体mRNA数量没有差异，在瘦素受体cDNA 668位检测到序列多态性（A—>G），这第二次碱基替换使瘦素受体蛋白223位的谷氨酰胺变为精氨酸。在15个研究对象中，11个为杂合子，3个为纯合子。在研究人群中，多态性等位基因的发生与BMI无关。导致db/db小鼠瘦素受体缺陷的突变在任何肥胖的人身上都没有发现，fa/fa大鼠的突变也没有发现。这些结果提供了证据，证明在肥胖人群中观察到的瘦素抵抗不是由于瘦素受体的缺陷。
Leptin-receptor gene expression in hypothalamic tissue from lean and obese humans was examined. The full-length leptin receptor, that is believed to transmit the leptin signal, is expressed in human hypothalamus. There was no difference in the amount of leptin-receptor mRNA in seven lean (BMI 23.3 +/- 0.9 kg/m(2)) and eight obese (BMI 36.9 +/- 1.5) subjects as determined by reverse transcription-polymerase chain reaction, A sequence polymorphism (A-->G) was detected at position 668 of the leptin receptor cDNA, This second base substitution changed a glutamine to an arginine at position 223 of the leptin receptor protein. Of 15 subjects analyzed, 11 were heterozygous for this base change and 3 were homozygous, The occurance of the polymorphic allele(s) did not correlate with BMI in the population studied. The mutation responsible for the defect in the leptin receptor in db/db mice was not detected in any obese human, nor was the fa/fa rat mutation. These results provide evidence that the leptin resistance observed in obese humans is not due to a defect in the leptin receptor.