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Journal of Lipid Research, Vol 34, 1057-1091, Copyright © 1993 by Lipid Research, Inc.
M Lafontan and M Berlan
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).
REVIEWS
Fat cell adrenergic receptors and the control of white and brown fat cell function
Institut National de la Sante et de la Recherche Medicale, INSERM, Unite 317, Institut Louis Bugnard, Faculte de Medecine, CHU Rangueil, Toulouse, France.
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