Scarpace P J, Baresi L A, Morley J E
Geriatric Research Education and Clinical Center, Veterans Administration Medical Center, Sepulveda, California 91343.
Am J Physiol. 1987 Dec;253(6 Pt 1):E629-35. doi: 10.1152/ajpendo.1987.253.6.E629.
Thermogenesis in brown adipose tissue (BAT) serves as a regulator of body temperature and weight maintenance. Thermogenesis can be stimulated by catecholamine activation of adenylate cyclase through the beta-adrenergic receptor. To investigate the effects of sucrose feeding, food deprivation, and cold exposure on the beta-adrenergic pathway, adenylate cyclase activity and beta-adrenergic receptors were assessed in rat BAT after 2 wk of sucrose feeding, 2 days of food deprivation, or 2 days of cold exposure. beta-Adrenergic receptors were identified in BAT using [125I]iodocyanopindolol. Binding sites had the characteristics of mixed beta 1- and beta 2-type adrenergic receptors at a ratio of 60/40. After sucrose feeding or cold exposure, there was the expected increase in BAT mitochondrial mass as measured by total cytochrome-c oxidase activity but a decrease in beta-adrenergic receptor density due to a loss of the beta 1-adrenergic subtype. This BAT beta-adrenergic receptor downregulation was tissue specific, since myocardial beta-adrenergic receptors were unchanged with either sucrose feeding or cold exposure. In contrast, food deprivation did not alter BAT beta-adrenergic receptor density. Forskolin-stimulated adenylate cyclase activity increased in BAT after sucrose feeding or cold exposure but not after food deprivation. The ratio of isoproterenol-stimulated to forskolin-stimulated adenylate cyclase activity decreased in the sucrose-fed and cold-exposed rats but not in the food-deprived rats. These data suggest that in BAT, sucrose feeding or cold exposure result in downregulation of beta-adrenergic receptors and that isoproterenol-stimulated adenylate cyclase activity was limited by receptor availability.
棕色脂肪组织（BAT）中的产热作用是体温和体重维持的调节机制。儿茶酚胺可通过β-肾上腺素能受体激活腺苷酸环化酶，从而刺激产热。为了研究蔗糖喂养、禁食和冷暴露对β-肾上腺素能通路的影响，在大鼠经2周蔗糖喂养、2天禁食或2天冷暴露后，对其BAT中的腺苷酸环化酶活性和β-肾上腺素能受体进行了评估。使用[125I]碘氰吲哚洛尔在BAT中鉴定β-肾上腺素能受体。结合位点具有混合的β1和β2型肾上腺素能受体特征，比例为60/40。蔗糖喂养或冷暴露后，通过总细胞色素c氧化酶活性测定，BAT线粒体质量出现预期增加，但由于β1-肾上腺素能亚型的丧失，β-肾上腺素能受体密度降低。这种BATβ-肾上腺素能受体下调具有组织特异性，因为心肌β-肾上腺素能受体在蔗糖喂养或冷暴露后均未改变。相比之下，禁食并未改变BATβ-肾上腺素能受体密度。蔗糖喂养或冷暴露后，福斯可林刺激的腺苷酸环化酶活性在BAT中增加，但禁食后未增加。异丙肾上腺素刺激的腺苷酸环化酶活性与福斯可林刺激的腺苷酸环化酶活性之比在蔗糖喂养和冷暴露的大鼠中降低，但在禁食的大鼠中未降低。这些数据表明，在BAT中，蔗糖喂养或冷暴露会导致β-肾上腺素能受体下调，且异丙肾上腺素刺激的腺苷酸环化酶活性受受体可用性限制。
