Recent research suggests that leptin may control body weight by regulating energy expenditure and energy intake in mice. To explore the possible role of leptin in the regulation of energy expenditure in humans, we used doubly-labeled water methodology to determine whether fasting plasma leptin concentrations were related to total daily energy expenditure (TEE) and its components, resting energy expenditure (REE) and physical activity energy expenditure (PAEE), in free-living older African-American men (n = 21) and women (n = 25). Plasma leptin concentrations were higher in women than men, even after the adjustment for differences in fat mass (28 ± 3 ng/ml for women vs. 17 ± 3 ng/ml for men; P < 0.01). The logarithm of plasma leptin concentrations correlated with fat mass in both women (r = 0.80) and men (r = 0.78) (P < 0.0001). After statistical adjustment for sex differences in fat-free mass and fat mass, women had lower TEE (22%) and REE (15%) (P < 0.01) and a trend (P = 0.08) toward lower PAEE, compared with men. After controlling for the effects of fat-free mass on energy expenditure, plasma leptin concentrations were related to REE (r = 0.68, P < 0.001) and tended to be related to TEE (r = 0.37, P = 0.07) in African-American women but not men (r = 0.18 and −0.03, respectively). Plasma leptin concentrations were not related to PAEE in either men or women. These results suggest that leptin may contribute to the regulation of TEE in older African-American women through its effects on resting energy metabolism, but the role of leptin in the regulation of energy expenditure is less apparent in older African-American men.

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