Reciprocal relation of food intake and sympathetic activity: experimental observations and clinical implications

The neuropeptides, monoamines and many drugs involved with modulating food intake and fat stores have reciprocal effects on sympathetic activity and t hermogenesis. Both serotonin, acting through 5HT(1B/2C) receptors, and nore pinephrine acting through beta(2) and/or beta(3) receptors reduce food inta ke and augment sympathetic activity. Neuropeptide Y, beta-endorphin, orexin , galanin and melanin concentrating hormone all increase food intake and, w here tested, reduce sympathetic activity. In contrast, a larger number of p eptides including cholecystokinin, corticotrophin-releasing hormone/urocort in, enterostatin, leptin, CART and alpha-MSH reduce food intake and increas e sympathetic activity. Nicotine, prostaglandin, dexfenfluramine and sibutr amine also have this reciprocal effect on feeding and sympathetic nervous s ystem (SNS) activity. Chronic administration of neuropeptide Y (NPY) can pr oduce chronically increased food intake and obesity. This syndrome is simil ar to the ventromedial hypothalamus (VMH) syndrome and suggests that NPY mu st be acting as an inhibitory signal to stimulate a feeding system and inhi bit sympathetic activity. The melanocortin receptor system may be particula rly important in modulating food intake, because a transgenic mouse which d oes not express melanocortin-4 receptors is massively overweight. Adrenal g lucocorticoids are important in obesity since adrenalectomy will reverse or prevent the development of all forms of obesity. The clinical importance o f the sympathetic nervous system and food intake is emphasized by the inver se relation of sympathetic activity and body fat. The inhibition of food in take, lower body fat stores and higher energy expenditure in smokers also s upport this hypothesis. The reciprocal relationship between food intake and sympathetic activity is robust, suggesting that beta receptors in the peri phery and brain may be involved in the control of feeding and a reduction i n food intake in humans accounts for most of the weight loss with ephedrine and caffeine. We conclude that the inhibition of feeding by activating the SNS is an important satiety system which helps regulate body fat stores.