Unresponsiveness of the endorphinergic system to its physiological feedback in obesity.

Beta-endorphin (beta-Ep) plasma levels are higher in obese patients than in normal subjects. To establish that this finding constitutes hyperendorphinemia, 28 obese patients aged 12-55 years, six males and 22 females, (weighing 61-117 kg) were investigated twice by an overnight 1-mg p.o. dose dexamethasone suppression test (DST) before and after weight loss. beta-Ep was measured by radioimmunoassay (RIA). Before body weight loss, beta-Ep was higher than normal and unresponsive to DST, whereas ACTH and cortisol were suppressible. After weight loss, beta-Ep was slightly reduced but still insensitive to DST. ACTH and cortisol were responsive as usual. Findings suggest a resistance to DST in obesity as far as beta-Ep is concerned. The disorder persists even after weight loss, indicating that hyperendorphinemia is not secondary to body weight excess. Accordingly, one can argue that the unresponsiveness of the endorphinergic system to its physiological feedback is a pathophysiological characteristic of obesity.