Heterozygosity forLepob orLeprdb affects body composition and leptin homeostasis in adult mice

In an effort to understand the genetics of human obesity, we have studied the physiology and molecular genetics of rodent models with monogenetic forms of obesity including the leptin gene-defective (Lepob /Lepob ) and leptin receptor gene-defective (Leprdb /Leprdb ) mouse. In the experiments reported here, we investigated the effects of heterozygosity atLepob andLeprdb on body composition and circulating leptin concentration in +/+,Leprdb /+, andLepob /+ adult mice to identify possible gene dosage effects of these mutations that might elucidate their physiology. Adult mice heterozygous for theLepob orLeprdb allele had equivalent fat mass and percentage body fat, which was increased 27–47% and 23–35%, respectively, relative to +/+ littermates. Plasma leptin concentrations adjusted for fat mass were 6.5 ng/ml in theLepob /+, 9.6 ng/ml in the +/+, and 11.5 ng/ml in theLeprdb /+ mice. Sex had no effect on plasma leptin after controlling for fat mass. These data, and data from a small number of mice heterozyg...