Objective: To examine the determinants of plasma leptin levels and leptin resistance in a sample of extremely obese subjects and their relatives.
Design and method: We obtained plasma leptin values on 968 individuals from 218 families having both extremely obese and average weight members for obesity related variables. Multivariate regression analyses were used to identify predictors of both plasma leptin concentration and an index of leptin resistance. Family correlations and heritabilities were computed for plasma leptin and indices of leptin resistance.
Results: Body mass index and sex predicted 63% of the variance in plasma leptin. Extremely obese subjects were most likely and average weight subjects least likely to be leptin resistant. Both leptin and leptin resistance aggregated within families.
Conclusion: Leptin resistance is strongly associated with extreme obesity and appears to be a heritable trait. The determination of its genetic causes will aid in understanding the role of leptin in common forms of human obesity.