Considine R V, Considine E L, Williams C J, Hyde T M, Caro J F
Division of Endocrinology and Metabolism, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Diabetes. 1996 Jul;45(7):992-4. doi: 10.2337/diab.45.7.992.
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/m2) 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 occurrence [correction of 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.
对瘦人和肥胖者下丘脑组织中的瘦素受体基因表达进行了检测。被认为可传递瘦素信号的全长瘦素受体在人类下丘脑中表达。通过逆转录 - 聚合酶链反应测定，7名瘦人（BMI 23.3±0.9 kg/m²）和8名肥胖者（BMI 36.9±1.5）的瘦素受体mRNA量没有差异。在瘦素受体cDNA的668位检测到一个序列多态性（A→G）。这第二个碱基替换使瘦素受体蛋白223位的谷氨酰胺变为精氨酸。在所分析的15名受试者中，11名是该碱基变化的杂合子，3名是纯合子。在所研究的人群中，多态性等位基因的出现与BMI无关。在任何肥胖人类中均未检测到导致db/db小鼠瘦素受体缺陷的突变，也未检测到fa/fa大鼠突变。这些结果提供了证据，表明在肥胖人类中观察到的瘦素抵抗并非由于瘦素受体缺陷所致。
