Fat cell adrenergic receptors and the control of white and brown fat cell function

Five adrenoceptor subtypes are involved in the adrenergic regulation of white and brown fat cell function. The effects on cAMP production and cAMP-related cellular responses are mediated through the control of adenylyl cyclase activity by the stimulatory beta 1-, beta 2-, and beta 3-adrenergic receptors and the inhibitory alpha 2-adrenoceptors. Activation of alpha 1-adrenoceptors stimulates phosphoinositidase C activity leading to inositol 1,4,5-triphosphate and diacylglycerol formation with a consequent mobilization of intracellular Ca2+ stores and protein kinase C activation which trigger cell responsiveness. The balance between the various adrenoceptor subtypes is the point of regulation that determines the final effect of physiological amines on adipocytes in vitro and in vivo. Large species-specific differences exist in brown and white fat cell adrenoceptor distribution and in their relative importance in the control of the fat cell. Functional beta 3-adrenoceptors coexist with beta 1- and beta 2-adrenoceptors in a number of fat cells; they are weakly active in guinea pig, primate, and human fat cells. Physiological hormones and transmitters operate, in fact, through differential recruitment of all these multiple alpha- and beta-adrenoceptors on the basis of their relative affinity for the different subtypes. The affinity of the beta 3-adrenoceptor for catecholamines is less than that of the classical beta 1- and beta 2-adrenoceptors. Conversely, epinephrine and norepinephrine have a higher affinity for the alpha 2-adrenoceptors than for beta 1-, 2-, or 3-adrenoceptors. Antagonistic actions exist between alpha 2- and beta-adrenoceptor-mediated effects in white fat cells while positive cooperation has been revealed between alpha 1- and beta-adrenoceptors in brown fat cells. Homologous down-regulation of beta 1- and beta 2-adrenoceptors is observed after administration of physiological amines and beta-agonists. Conversely, beta 3- and alpha 2-adrenoceptors are much more resistant to agonist-induced desensitization and down-regulation. Heterologous regulation of beta-adrenoceptors was reported with glucocorticoids while sex-steroid hormones were shown to regulate alpha 2-adrenoceptor expression (androgens) and to alter adenylyl cyclase activity (estrogens).