Mutation in the leptin receptor (Leprfa) 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 Leprfa. Because the plasma of neonatal rats contains leptin, although their adipocytes contain virtually no triglyceride, we determined whether mutation dose-dependent differences in plasma leptin concentration exist before the postnatal onset of triglyceride storage. Plasma samples were obtained 10 min after birth of each rat pup and leptin concentration determined by radioimmunoassay. Plasma leptin 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-way 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). Leprfa gene dose-dependent elevations in plasma leptin are, therefore, present at birth and constitute the only Leprfa-related phenotypic trait presently known to precede the onset of increased fat storage.