Fat cell adrenergic receptors and the control of white and brown fat cell function.
Fat cell adrenergic receptors and the control of white and brown fat cell function.
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发表时间：
1993-07
影响因子：
6.5
通讯作者：
M. Lafontan;M. Berlan
中科院分区：
文献类型：
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作者：
M. Lafontan;M. Berlan
五种肾上腺素受体亚型参与白色和棕色脂肪细胞功能的肾上腺素能调节。对cAMP产生和cAMP相关细胞反应的影响是通过刺激性β 1-、β 2-和β 3-肾上腺素能受体和抑制性α 2-肾上腺素能受体控制腺苷酸环化酶活性介导的。α 1-肾上腺素能受体的激活刺激磷酸肌醇酶C活性，导致肌醇1，4，5-三磷酸和二酰基甘油形成，随后动员细胞内Ca 2+储存和蛋白激酶C激活，从而触发细胞反应性。各种肾上腺素受体亚型之间的平衡是调节点，其决定了生理胺在体外和体内对脂肪细胞的最终作用。棕色和白色脂肪细胞肾上腺素能受体的分布及其在控制脂肪细胞中的相对重要性存在较大的种属特异性差异。功能性β 3肾上腺素受体与β 1和β 2肾上腺素受体共存于许多脂肪细胞中;它们在豚鼠、灵长类动物和人类脂肪细胞中活性较弱。事实上，生理激素和递质的作用是通过对所有这些多种α-和β-肾上腺素受体的不同募集来实现的，这些募集是基于它们对不同亚型的相对亲和力。β 3-肾上腺素受体对儿茶酚胺的亲和力低于经典的β 1-和β 2-肾上腺素受体。相反，肾上腺素和去甲肾上腺素对α 2-肾上腺素受体的亲和力高于对β 1-、β 2-或β 3-肾上腺素受体的亲和力。在白色脂肪细胞中，α 2-和β-肾上腺素受体介导的效应之间存在拮抗作用，而在棕色脂肪细胞中，α 1-和β-肾上腺素受体之间存在正合作。在给予生理胺和β-激动剂后，观察到β 1-和β 2-肾上腺素受体的同型半胱氨酸下调。相反，β 3-和α 2-肾上腺素受体对激动剂诱导的脱敏和下调更有抵抗力。据报道，糖皮质激素对β-肾上腺素受体具有异源调节作用，而性类固醇激素则可调节α 2-肾上腺素受体表达（雄激素）并改变腺苷酸环化酶活性（雌激素）。
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).