Evidence for Leptin Regulation of Food Intake

The adipocyte hormone leptin regulates body weight in mice by decreasing food intake and increasing energy expenditure. Whether leptin is of physiological importance for these processes in humans is, however, not clear. We therefore studied the relation between leptin and habitual food intake in 64 healthy postmenopausal women. Dietary habits were assessed with a modified diet history method. Body fat content was measured using bioelectrical impedance. In the 64 women, aged 58.6 6 0.4 yr (mean 6 SD), serum leptin was 19.3 6 12.7 ng/mL, body mass index was 25.0 6 3.5 kg/m, body fat content was 31.6 6 4.3%, fasting glucose was 4.6 6 0.5 mmol/L, and fasting insulin was 56 6 21 pmol/L. Leptin levels were negatively correlated to total energy intake (r 5 20.34; P 5 0.006), carbohydrate intake (r 5 20.36; P 5 0.004), and total (r 5 20.27; P 5 0.034) as well as saturated fat intake (r 5 20.31; P 5 0.014). Leptin was correlated to the absolute, but not to the percent, intake of these nutrients. When normalized for body fat content, the correlations remained significant. Our results suggest that plasma leptin is involved in the physiological regulation of food intake in humans, and that leptin is related to the quantity rather than the quality of habitual food intake. (J Clin Endocrinol Metab 83: 4382–4385, 1998) L is produced in adipose tissue and is known to regulate body weight in mice. Thus, leptin administration inhibits food intake (1, 2) through a central effect on leptin receptors in the hypothalamus (3, 4), and increases energy expenditure through activating the sympathetic nervous system (5, 6) and uncoupling protein-2 (7, 8). In addition, the importance of endogenous leptin for the regulation of food intake in rats was recently demonstrated using leptin antibodies (9). The combined effects of leptin on food intake and energy expenditure reduce body weight in rodents. In humans, however, the physiological role of leptin is still unclear. It is known that plasma leptin levels are increased in obese humans (10, 11), suggesting that leptin is released from the adipose tissue in relation to adiposity. Furthermore, evidence for long term regulation of body weight by leptin has been presented in Pima Indians (12). Whether these effects are mediated by changes in food intake and/or energy expenditure is not known. Recently, there have been conflicting reports on the relation between leptin and energy expenditure in humans (13–15), whereas the physiological effects of leptin on food intake are unknown. It is known from animal experiments that neuropeptides and hormones can affect the intake of specific nutrients (16, 17). For example, in rats, central administration of neuropeptide Y (NPY) stimulates the intake of carbohydrates (18, 19) as opposed to fat intake, which is increased by galanin (20). As leptin has been demonstrated to inhibit NPY in the rat hypothalamus (4, 21, 22), it is conceivable that leptin, in addition to regulating total energy intake, is related to qualitative aspects of food intake. Our aim was to determine whether leptin levels are associated with habitual intake of energy or specific nutrients in humans. We therefore related plasma leptin levels in healthy women to their dietary habits as assessed by a combined method of a food frequency questionnaire and a 7-day menu book. Subjects and Methods