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

George Stratigopoulos, Charles A. LeDuc, Naoki Matsuoka, Roee Gutman, Richard Rausch, Scott A. Robertson, Martin G. Myers, Wendy K. Chung, Streamson C. Chua, Jr., Rudolph L. Leibel

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)126-135
Number of pages10
JournalObesity
Volume17
Issue number1
DOIs
StatePublished - Jan 23 2009

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Adiposity
Alleles
Leptin
Genetic Association Studies
Body Composition
Codon
Energy Metabolism
Fats
Body Weight
Diet
human leptin receptor

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Stratigopoulos, G., LeDuc, C. A., Matsuoka, N., Gutman, R., Rausch, R., Robertson, S. A., ... Leibel, R. L. (2009). Functional consequences of the human leptin receptor (LEPR) Q223R transversion. Obesity, 17(1), 126-135. https://doi.org/10.1038/oby.2008.489

Functional consequences of the human leptin receptor (LEPR) Q223R transversion. / Stratigopoulos, George; LeDuc, Charles A.; Matsuoka, Naoki; Gutman, Roee; Rausch, Richard; Robertson, Scott A.; Myers, Martin G.; Chung, Wendy K.; Chua, Jr., Streamson C.; Leibel, Rudolph L.

In: Obesity, Vol. 17, No. 1, 23.01.2009, p. 126-135.

Research output: Contribution to journalArticle

Stratigopoulos, G, LeDuc, CA, Matsuoka, N, Gutman, R, Rausch, R, Robertson, SA, Myers, MG, Chung, WK, Chua, Jr., SC & Leibel, RL 2009, 'Functional consequences of the human leptin receptor (LEPR) Q223R transversion', Obesity, vol. 17, no. 1, pp. 126-135. https://doi.org/10.1038/oby.2008.489
Stratigopoulos G, LeDuc CA, Matsuoka N, Gutman R, Rausch R, Robertson SA et al. Functional consequences of the human leptin receptor (LEPR) Q223R transversion. Obesity. 2009 Jan 23;17(1):126-135. https://doi.org/10.1038/oby.2008.489
Stratigopoulos, George ; LeDuc, Charles A. ; Matsuoka, Naoki ; Gutman, Roee ; Rausch, Richard ; Robertson, Scott A. ; Myers, Martin G. ; Chung, Wendy K. ; Chua, Jr., Streamson C. ; Leibel, Rudolph L. / Functional consequences of the human leptin receptor (LEPR) Q223R transversion. In: Obesity. 2009 ; Vol. 17, No. 1. pp. 126-135.
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