Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution

BACKGROUND: Circulating concentrations of leptin normalized to total adipos e tissue mass are significantly greater in females than in males. Rates of leptin expression (per gram of adipose tissue) are significantly greater in subcutaneous (SAT) than visceral (VAT) adipose tissue and the relative amo unt of fat stored as SAT vs VAT is significantly greater in pre-menopausal females than in males. Gender-related differences in the relative amounts o f SAT and VAT may account for the greater circulating leptin concentration relative to fat-mass in females than males. METHODS: We examined body composition and anatomic fat distribution by dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), a nd post-absorptive circulating concentrations of leptin and insulin in 58 s ubjects (26 females, 32 males). Stepwise multiple linear regression analyse s, treating gender as a dichotomous variable, were performed to determine i nter-relationships among leptin concentrations and insulin concentrations, VAT and SAT. RESULTS: Body composition by DEXA and MRI were highly correlated (r(2) = 0. 97, P < 0.0001). There were significant gender effects on leptin/total fat mass (males, 0.17 +/- 0.01 ng/ml/kg; females, 0.49 +/- 0.05 ng/ml/kg; P < 0 .0001) and relative amounts of fat in SAT and VAT depots (ratio of SAT/VAT, males, 12.3 +/- 1.5; females, 32.9 +/- 3.2; P < 0.0001). Circulating lepti n concentration was significantly correlated with insulin concentration (P = 0.001), SAT (P < 0.0001) and gender (P = 0.033). Circulating concentratio ns of insulin were significantly correlated with VAT, but not SAT, in males and with SAT, but not VAT, in females. CONCLUSIONS: The sexual dimorphism in the relationship between leptin and a dipose tissue mass cannot be explained by differences in the relative amoun ts of VAT and SAT. Thus, the sexual dimorphism in plasma leptin concentrati on appears to reflect, at least in part, effects of circulating concentrati ons of gonadal steroids (especially androgens) and/or primary genetic diffe rences that are independent of amounts of VAT or SAT.