0021.972x/96/$03.00/0 Journal of Clinical Endocrinology and Metabolism Copyright 0 1996 by The Endocrine Society Vol. 81, No. 9 Printed in U.S.A. EFFECTS OF GENDER, BODY COMPOSITION, AND MENOPAUSE ON PLASMA CONCENTRATIONS OF LEPTIN MICHAEL ROSENBAUM*, MARGERY NICOLSON, JULES HIRSCH, STEVEN B. HEYMSFIELD, DYMPNA GALLAGHER, FLORENCE CHU, AND RUDOLPH L. LEIBEL Laboratory of Human Behavior and Metabolism, Rockefeller University, New York, NY 10021 (M.R, J.H., F.C., R.L.); Obesity Research Center, Department of Medicine, St. Luke’s-Roosevelt Hospital Center, New York, NY, 10025 (S.B.H., D.G.); and Amgen Inc., Thousand Oaks, CA 91329-1789 (M.N.). ABSTRACT: Circulating concentrations of leptin ([leptin]) vary directly with body mass index and percentage body fat, and may thus constitute an afferent limb of a system regulating body fatness. We tested the hypotheses that: 1). Plasma [leptin] vary more directly with absolute fat mass than with fractional body fatness per se; and 2). The relationship between fat mass and [leptin] is significantly affected by gender and by menopausal status. [Leptin] in the post-absorptive state was examined in 67 subjects (26 male, 20 premenopausal female, 21 post- menopausal females; 43 never-obese, 24 obese) at usual body weight. Body composition was determined by hydrodensitometry, and [leptin] wase determined by a double antibody ELISA assay. In male and pre-menopausal female subjects, subcutaneous adipose tissue aspirations were performed for determination of adipocyte volume by the osmium fixation method, and a 3 hour oral glucose tolerance tests was performed. At usual body weight, ([leptin] was better correlated with absolute fat mass than with body mass index (BMI) or percentage body fat. BMI and % body fat did not account for any of the variance in [leptin] beyond that attributable to FM, per se. The regression equations relating FM to [leptin] did not dither significantly between obese and never-obese subjects. [Leptin] and fasting serum insulin concentrations were significantly correlated in males only. [Leptin] was significantly higher in pre- and post-menopausal females compared to males, even when [leptin] was corrected for differences in body composition @e-menopausal females > post-menopausal females > males). While plasma [leptin], corrected for FM, declines significantly in women post-menopause, this decline is not sufficient to account for the striking sexual dimorphism in the relationship of leptin to fat mass. This sexual dimorphism is apparently also due, in part, to a suppressive effect of circulating androgens on [leptin]. INTRODUCTION for at least 6 months prior to enrollment. Females Leptin is secreted from adipose tissue[l] and appears to be a component of a regulatory loop linking fat mass to food intake and energy expenditure[2-41. Previous studies have reported a significant correlation between measures of body fatness (body mass index[BMI, Wt (kg)/@ (m))2, % body fat) and circulating concentrations of leptin in adults[Matfei, 1996 #1454;Considine, 1996 #1467], but specific effects of absolute fat mass and lean body mass have not been previously reported. We measured plasma concentrations of leptin and body composition in obese and never-obese humans at who were classified as post-menopausal had not menstruated for at least 7 years (range 7 to 32 years, MeanfSE = 13.8f1.3 years) prior to enrollment, while females classifed as pre-menopausal were menstruating regularly. Subjects with body mass index (BMI, [Wt (kg)]/[Ht (m)12) >28 kg/m2 were classified as obese and subjects with BMI<28 kg/m2 were classified as never-obese[5]. All subjects were in good health and taking no medications. All studies were approved by the Institutional Review Boards of the Rockefeller University Hospital and St. Luke’sfioosevelt Hospital Medical Center. All usual body weight. This was done to determine: 1). The relationship of plasma leptin concentrations ([leptin]) to (FM); 2). Whether the relationship between between [leptin] and FM is significantly affected by gender and/or by menopausal status. subjects gave written informed consent was prior to enrollment. Subject characteristics are presented in Table 1. Body composition was measured in all subjects by hydrodensitometry[6]. Post-absorptive [leptin] was measured by a solid phase sandwich enzyme METHODOLOGY immunoassay using an afIinity purified polyvalent All subjects were at their maximal lifetime weight antibody immobilized in microliter wells. Bound and had maintained this weight within a 2 kg range leptin was detected with affinity purified antibody * Correspondent: Michael Rosenbaum, M.D., Rockefeller University, Laboratory of Human Behavior and Metabolism, 1230 York Avenue, New York, NY,10021. 3424 Downloaded from https://academic.oup.com/jcem/article/81/9/3424/2651141 by guest on 25 June 2022