Background: Obesity in Prader-Willi syndrome (PWS) may be related to abnormalities in the adipocyte-leptin-hypothalamic pathway and may be exacerbated by reductions in the resting metabolic rate (RMR).
Objective: We compared body composition, body-composition- adjusted RMR, and adiposity-adjusted plasma leptin between women with PWS and control women. We also examined leptin receptor expression in the PWS group.
Design: We studied body composition using whole-body magnetic resonance imaging and measured plasma leptin by radioimmunoassay in 45 control women aged 18-56 y and in 13 women with PWS aged 20-38 y. RMR was measured by indirect calorimetry in 41 control women and in 8 women with PWS. Age, body composition, and regional adipose tissue (AT) depots were corrected for by multiple regression analysis. Messenger RNA expression of the leptin receptor was examined by reverse transcriptase-polymerase chain reaction in lymphocytes.
Results: In the PWS group, fat mass was greater after correction for fat-free mass, and RMR was normal after correction for both fat-free mass and fat mass. Leptin was influenced primarily by subcutaneous AT volume in both subject groups. Leptin concentrations were not significantly different between the 2 groups after adjustment for age and AT content or distribution. Full-length leptin receptor messenger RNA was expressed in the lymphocytes of the PWS group.
Conclusions: Differences in RMR in women with PWS are explained by abnormal body composition, suggesting that energy expenditure is normal at the tissue level in PWS. There is no evidence that defective leptin production causes obesity in PWS, and leptin receptor deficiency is not a primary consequence of the gene defects leading to leptin resistance.