Genetic variation of circulating leptin is involved in genetic variation of hand bone size and geometry.

Leptin is secreted primarily by the adipocytes and plays an important role in the regulation of food intake and energy expenditure. In addition to its adipostatic function, it has been demonstrated that leptin directly enhances stromal cell differentiation to osteoblasts, and since such precursor cells are potential targets for leptin, the latter could possibly mediate the relationship between obesity and bone mass and size. To address this question, we studied phenotypic and genetic correlations between the circulating levels of leptin and hand bone size (BS) and geometry (BG) of the radiographic hand in a healthy and ethnically homogeneous sample of pedigrees. We also attempted to evaluate to what extent potential leptin/BS/BG correlations are modified by an individual's obesity traits, specifically his/her BMI. Our research has shown that leptin, BMI and the corresponding bone measures are clearly inherited traits (0.46+/-0.11, 0.35+/-0.16, 0.62+/-0.12 and 0.51+/-0.09, respectively). The bivariate variance component analysis revealed very strong and significant genetic and environmental correlations between circulating leptin and BMI ( r(G)=0.86+/-0.09, r(E)=0.75+/-0.05, P<0.001). Furthermore, genetic correlations between leptin and hand bone characteristics proved inverse and statistically significant ( r(G)=-0.35+/-0.01 and -0.45+/-0.10 for BS and BG, respectively), while corresponding environmental correlations were low ( r(E)=-0.14+/-0.15 and -0.07+/-0.14) and they could be constrained to zero without significant deterioration of the model fit to the data ( P>0.10). However, despite the extremely strong relationship between leptin and BMI, we failed to detect phenotypic or genetic correlations between BMI and our two hand bone measures. Thus our study provided evidence that plasma leptin levels may be statistically significant predictor of hand bone size and geometry, and may play a physiological role in maintaining bone mass as well as in regulation of hand bone proportions.