Mutation in the leptin receptor (Lepr(fa)) causes fat-storage-independent hyperleptinaemia in neonatal rats

The plasma leptin concentration adjusted for fat mass is affected by mutant gene dosage in older animals segregating for Lepr(fa). Because the plasma of neonatal rats contains leptin, although their adipocytes contain virtual ly no triglyceride, we determined whether mutation dose-dependent differenc es in plasma leptin concentration exist before the postnatal onset of trigl yceride storage. Plasma samples were obtained 10 min after birth of each ra t pup and leptin concentration determined by radioimmunoassay. Plasma lepti n in homozygous wild-type (+/+) pups was 1.6+/-0.2 ng/ml (n=20) and 2.4+/-0 .2 ng/ml in +/fa (n=32) littermates (least-square means+/-SE, P<0.05, two-w ay ANOVA with litter and genotype as factors). The corresponding values for +/fa (n=21) and fa/fa (n=15) littermates were 2.4+/-0.2 and. 4.0+/-0.3 ng/ ml respectively (P<0.001). Lepr(fa) gene dose-dependent elevations in plasm a leptin are, therefore, present at birth and constitute the only Lepr(fa)- related phenotypic trait presently known to precede the onset of increased fat storage.