SERUM LEPTIN LEVELS IN WOMEN WITH ANOREXIA-NERVOSA

Leptin is a protein encoded by the ob gene that is expressed in adipoc ytes and regulates eating behavior via central neuroendocrine mechanis ms. Serum leptin levels have been shown to correlate with weight and p ercent body fat in normal and obese individuals; however, it is not kn own whether the regulation of leptin is normal below a critical thresh old of body fat in chronic undernutrition. We investigated serum lepti n levels in 22 women, aged 23 +/- 4 yr, with anorexia nervosa. Duratio n of disease, weight, BMI, percent body fat, and serum leptin levels w ere determined for each patient. Nutritional status was assessed furth er by caloric intake and measurement of insulin and insulin-like growt h factor I (IGF-I) levels. Twenty-three healthy women, aged 23 +/- 4 y r, taking no medications, with normal menstrual function and body mass index (BMI) between 20-26 kg/m(2) (mean, 23.7 +/- 1.7 kg/m(2)), serve d as a control population for compar ison of leptin levels. Subjects w ith anorexia nervosa were low weight (BMI, 16.3 +/- 1.6 kg/m(2); norma l, 20-26 kg/m(2)) and exhibited a striking reduction in percent body f at (7 +/- 2%; normal, 20-30%). The mean serum leptin level was signifi cantly decreased in subjects with anorexia nervosa compared with that in age- and sex-matched controls of normal body weight (5.6 +/- 3.7 vs . 19.1 +/- 8.1 ng/mL; P < 0.0001). Serum leptin levels were correlated highly with weight, as expressed either BMI (r = 0.66; P = 0.002) or percent ideal body weight (r = 0.68; P = 0.0005), body fat (r = 0.70; P = 0.0003), and IGF-I (r = 0.64; P = 0.001), but not with caloric int ake or serum levels of estradiol or insulin in subjects with anorexia nervosa. The correlation between leptin and body fat was linear, with progressively lower, but detectable, leptin levels measured even in pa tients with less than 5% body fat, but was not significant when the ef fects of weight were taken into account. In contrast, the correlation between leptin and IGF-I remained significant when the effects of weig ht, body fat, and caloric intake were taken into account. In normal co ntrols, leptin correlated with BMI (r = 0.55; P = 0.007) and IGF-I (r = 0.44; P < 0.05), but not with fat mass. These data demonstrate that serum leptin levels are reduced in association with low weight and per cent body fat in subjects with anorexia nervosa compared to normal con trols. Leptin levels correlate highly with weight, percent body fat, a nd IGF-I in subjects with anorexia nervosa, suggesting that the physio logical regulation of leptin is maintained in relation to nutritional status even at an extreme of low weight and body fat.