The hypothalamic leptin receptor in humans: Identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations

R. V. Considine, E. L. Considine, C. J. Williams, T. M. Hyde, J. F. Caro

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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 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.

Original languageEnglish (US)
Pages (from-to)992-994
Number of pages3
Issue number3 SUPPL.
StatePublished - Jul 19 1996


ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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