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Functional consequences of the human leptin receptor (LEPR) Q223R transversion.


ABSTRACT: Perturbations in the functional integrity of the leptin axis are obvious candidates for mediation of altered adiposity. In a large number of genetic association studies in humans, the nonconservative LEPR Q223R allele has been inconsistently associated with adiposity. Subtle, long-term effects of such genetic variants can be obscured by effects of the environment and other confounders that render definitive inferences difficult to reach. We directly assessed the biological effects of this variant in 129P3/J mice segregating for the humanized Lepr allele at codon 223. No effects of this allele were detected on body weight, composition, or energy expenditure in animals fed diets of varying fat content over periods as long as 235 days. In vitro, Q223R did not affect leptin signaling as reflected by activation of STAT3. We conclude that Q223R is unlikely to play a significant role in regulation of human adiposity. This approach to vetting of human allelic variation might be more widely used.

SUBMITTER: Stratigopoulos G 

PROVIDER: S-EPMC2808713 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Functional consequences of the human leptin receptor (LEPR) Q223R transversion.

Stratigopoulos George G   LeDuc Charles A CA   Matsuoka Naoki N   Gutman Roee R   Rausch Richard R   Robertson Scott A SA   Myers Martin G MG   Chung Wendy K WK   Chua Streamson C SC   Leibel Rudolph L RL  

Obesity (Silver Spring, Md.) 20081106 1


Perturbations in the functional integrity of the leptin axis are obvious candidates for mediation of altered adiposity. In a large number of genetic association studies in humans, the nonconservative LEPR Q223R allele has been inconsistently associated with adiposity. Subtle, long-term effects of such genetic variants can be obscured by effects of the environment and other confounders that render definitive inferences difficult to reach. We directly assessed the biological effects of this varian  ...[more]

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