CNS REGULATION OF THERMOGENESIS

Thermogenesis (adaptive increases in heat production) can develop in r esponse to low environmental temperature, alterations in the amount or composition of the diet, and pathogenic stimuli, such as infection, i njury, and inflammation. Thermogenic responses to each of these stimul i appear to be mediated by activation of the sympathetic nervous syste m and, at least in experimental animals, by heat production in brown f at. Thermogenesis is under the direct control by the central nervous s ystem (CNS), particularly by specific regions of the hypothalamus. Ser otonergic pathways have been directly implicated in the central contro l of most forms of thermogenesis, and indirect evidence suggests invol vement of adrenergic and cholinergic mechanisms. Numerous peptides hav e been shown to induce increases on metabolic rate when injected into the brains of experimental animals; of these, corticotrophin-releasing factor (CRF) has been the most extensively studied. CRF appears to me diate thermogenic responses to serotonergic agonists, injury, and cyto kines, and may be involved in impaired thermogenic responses in certai n genetically obese rodents. Cytokines, particularly interleukin-1 (IL -1) and IL-6, act as endogenous pyrogens in the brain and stimulate th ermogenesis via synthesis of prostaglandins and CRF. Peptides such as lipocortin-1, arginine vasopressin, and alphaMSH potently inhibit cent ral effects of cytokines. Pharmacological modification of thermogenesi s may be clinically beneficial in treating conditions such as obesity, cachexia, and fever.