GENDER DIFFERENCES IN THE RESPONSE OF PLASMA LEPTIN CONCENTRATIONS TOWEIGHT-LOSS IN OBESE OLDER INDIVIDUALS

Plasma leptin concentration is directly related to the degree of obesi ty and is higher in women than in men of the same body mass index (BMI ). We hypothesized that fasting plasma leptin concentrations and the r esponse of leptin to weight loss would differ in older men and women o f a similar fat mass. Plasma leptin concentrations (radioimmunoassay) and fat mass (DXA) mere measured in 47 older, obese (BMI=30 +/- 4 kg/m (2)) women and 23 older, obese (BMI=31 +/- 3 kg/m(2)) 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 wo men (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 simila r percentage of fat mass (-13% and -16%, respectively), but the relati ve decline in circulating leptin was greater in women than men (-45% a nd -21%, respectively; p<0.0001). In addition, when leptin was normali zed for fat mass using the ratio method, the decrease in leptin per ki logram 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 lept in 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 level s in women (r=-0.47; p<0.05), but not in men (r=0.03, p=NS). These res ults indicate that the decline in leptin concentration with weight los s correlates with the loss in fat mass in men; but, in women, other fa ctors 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 treatme nt and maintenance of lost weight.