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

• Published in: Diabetes (New York, N.Y.) Vol. 45; no. 7; pp. 992 - 994
• Main Authors: Considine, R. V., Considine, E. L., Williams, C. J., Hyde, T. M., Caro, J. F.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.1996
• Subjects: Animals; Arginine; Biological and medical sciences; Body Weight; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; DNA, Complementary; Gene Expression; Glutamine; Humans; Hypothalamus - metabolism; Medical sciences; Metabolic diseases; Mice; Mice, Mutant Strains; Obesity; Polymerase Chain Reaction; Polymorphism, Genetic; Rats; Rats, Mutant Strains; Receptors, Cell Surface; Receptors, Cytokine - biosynthesis; Receptors, Cytokine - genetics; Receptors, Leptin; RNA, Messenger - biosynthesis; Thinness; Human; Obesity; Target tissue resistance; Leptin; Central nervous system; Metabolic diseases; Hypothalamus; Mutation; Gene expression; Brain (vertebrata); Hormonal receptor
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.45.7.992

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 and J F Caro Division of Endocrinology and Metabolism, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Abstract 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.