Leptin's sexual dimorphism results from genotype by sex interactions mediated by testosterone.

Objective: Recent studies have reported the existence of marked sexual dimorphism in serum leptin levels in humans, with women having approximately three times the levels of men. As we have shown for other measures of adiposity, such sexual dimorphism can arise from a special case of genotype by environment interaction, that of genotype by sex interaction. Research Methods and Procedures: Using maximum likelihood-based variance decomposition techniques, we examined the genetic and environmental architecture of sexual dimorphism in serum leptin levels in 1147 Mexican Americans from the San Antonio Family Heart Study. Results: Both the genetic and environmental variances for this trait differed significantly between the sexes (p < 0.001 and p < 0.01, respectively), with women displaying larger values for both components. We found significant evidence that different genes influence variation in serum leptin levels between the two sexes (p = 0.05). Furthermore, this pattern of sexual dimorphism in serum leptin levels persisted even after accounting for the effects of either the percentage of body fat or total body fat. However, this pattern of sexual dimorphism was eliminated after accounting for the effects of testosterone. Discussion: These findings suggest that the sexual dimorphism seen in leptin levels is not simply explained as differences in total adiposity between the sexes. We conclude that the genes, which influence variation in serum leptin levels, are differentially expressed depending on sex, and that the sexes also show differences in response of the expression of this obesity-related trait to unmeasured residual effects.