Gender differences in the response of plasma leptin concentrations to weight loss in obese older individuals

Plasma leptin concentration is directly related to the degree of obesity and is higher in women than in men of the same body mass index (BMI). We hypothesized that fasting plasma leptin concentrations and the response of leptin to weight loss would differ in older men and women of a similar fat mass. Plasma leptin concentrations (radioimmunoassay) and fat mass (DXA) were measured in 47 older, obese (BMI = 30 +/- 4 kg/m2) women and 23 older, obese (BMI = 31 +/- 3 kg/m2) men after a 2 to 4 week period of weight and dietary stabilization, and then in 22 of the women and 18 of the men after a 6-month weight loss intervention (250-350 kcal/d deficit). Leptin correlated with fat mass in men and women (r = 0.75 and r = 0.77, respectively; p values < 0.0001), but women had 3-fold higher leptin levels for a given fat mass than men (p = 0.01). In response to the 6-month hypocaloric diet, men and women lost a similar percentage of fat mass (-13% and -16%, respectively), but the relative decline in circulating leptin was greater in women than men (-45% and -21%, respectively; p < 0.0001). In addition, when leptin was normalized for fat mass using the ratio method, the decrease in leptin per kilogram of fat mass was greater in women than men (-0.37 +/- 0.34 vs. -0.04 +/- 0.06 ng/mL/kg; p < 0.01). After weight loss, the change in leptin concentrations correlated positively with the change in fat mass in men (r = 0.60; p < 0.01), but not in women (r = 0.31; p = 0.17). Furthermore, the loss in fat mass correlated negatively with baseline leptin levels in women (r = -0.47; p < 0.05), but not in men (r = 0.03, p = NS). These results indicate that the decline in leptin concentration with weight loss correlates with the loss in fat mass in men; but, in women, other factors affect the decrease in leptin concentration. This suggests that the role of leptin in the regulation of obesity is gender-specific and may account for gender differences in response to hypocaloric treatment and maintenance of lost weight.