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Leptin responsiveness and gene dosage for leptin receptor mutation (fa) in newborn rats
S Kraeft1, K Schwarzer, S Eiden
1Max-Planck-Institut für physiologische und klinische Forschung, W. G. Kerckhoff-Institut, D-61231 Bad Nauheim, Germany.
Insights
Leptin receptor mutations reduce the body fat response to leptin in young rats. Even with high doses, pups with fatty (fa) alleles show diminished or absent fat reduction, indicating impaired leptin signaling.
Area of Science:
- Endocrinology
- Developmental Biology
- Genetics
Background:
- Leptin is a key hormone regulating energy balance and fat deposition.
- The leptin receptor plays a crucial role in mediating leptin's effects.
- Understanding early-life leptin signaling is vital for comprehending metabolic development.
Purpose of the Study:
- To investigate the impact of leptin receptor mutations (fa allele) on leptin responsiveness in neonatal rats.
- To determine if leptin influences fat deposition during the first postnatal week.
Main Methods:
- Recombinant leptin was administered daily to wild-type, heterozygous, and fatty rat pups from day 1 to day 7.
- Body mass and body fat content were compared between leptin-treated and saline-treated pups of the same genotype.
- Plasma leptin levels were monitored under different leptin dosage conditions.
Main Results:
- Leptin treatment slowed body mass gain in wild-type pups but not in heterozygous or fatty pups.
- Body fat content decreased by 37% in wild-type, 22% in heterozygous, and 0% in fatty pups.
- Response to leptin was dose-dependent, with supraphysiological doses showing reduced efficacy in pups with fa alleles.
Conclusions:
- Leptin is involved in controlling early fat deposition, even within the first postnatal week.
- The leptin receptor mutation (fa) significantly impairs or abolishes the response to leptin in neonatal rats.
- These findings highlight the critical role of functional leptin receptors in early metabolic regulation.
Abstract:
To determine the degree to which the leptin receptor mutation (fa) influences the responsiveness to leptin during the first postnatal week, we injected recombinant leptin (600 pmol. g-1. day-1 sc from day 1 to day 7) into wild-type (+/+), heterozygous (+/fa), and fatty (fa/fa) rat pups. Growth and final body fat content of these leptin-treated pups were compared with those of saline-treated littermates of the same genotype. The body mass of the leptin-treated +/+ pups, but not that of the +/fa and fa/fa pups, increased more slowly than that of their respective controls, and fat content at day 7 was reduced by 37% in +/+ pups, by 22% in +/fa pups, but not at all in fa/fa pups. Plasma leptin remained excessively high throughout the day under this treatment, but a 30-fold lower leptin dose, causing only moderate changes of plasma leptin, still reduced the body fat of +/+ pups significantly. We conclude that leptin participates in the control of even the earliest stages of fat deposition and that the response to supraphysiological doses of leptin is markedly reduced in 1-wk-old pups with one fa allele and absent in pups with two fa alleles.
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