The hypothalamic leptin receptor in humans: identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations.
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.
Considine
R V
RV
Division of Endocrinology and Metabolism, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Considine
E L
EL
Williams
C J
CJ
Hyde
T M
TM
Caro
J F
JF
D000818:Animals; D001120:Arginine; D001835:Body Weight; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D018076:DNA, Complementary; D015870:Gene Expression; D005973:Glutamine; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009765:Obesity; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011922:Rats, Mutant Strains; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D054411:Receptors, Leptin; D013851:Thinness
D002352:Carrier Proteins; D018076:DNA, Complementary; C515448:LEPR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D005973:Glutamine; D001120:Arginine