Immunohistochemical identification of the β3-adrenoceptor in intact human adipocytes and ventricular myocardium:: effect of obesity and treatment with ephedrine and caffeine

Immunohistochemical identification of the β3-adrenoceptor in intact human adipocytes and ventricular myocardium:: effect of obesity and treatment with ephedrine and caffeine
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DOI:
10.1038/sj.ijo.0802148
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发表时间:
2002-11-01
影响因子:
4.9
通讯作者:
Stock, MJ
Stock, MJ
中科院分区:
医学2区
文献类型:
--
作者:
De Matteis, R;Petroni, ML;Stock, MJ

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目的:研究β 3肾上腺素能受体是否可以通过免疫组织化学在完整的人白色和棕色脂肪细胞以及其他人体组织中鉴定,并研究肥胖及其用麻黄碱和咖啡因治疗对脂肪细胞中β 3肾上腺素能受体表达的影响。病态肥胖的病人被给予低能量饮食(70%的能量消耗),有些人还用麻黄碱和咖啡因(20/200毫克,每天三次)治疗4周。在手术过程中采集脂肪组织和其他组织。免疫组织化学染色用抗人β 3肾上腺素受体的单克隆抗体进行。所有白色脂肪细胞均染色。那些从瘦受试者和肥胖受试者与麻黄碱和咖啡因治疗显示出更强烈的染色比未经治疗的肥胖受试者。嗜铬细胞瘤患者肾周脂肪组织中棕色脂肪细胞的染色比白色脂肪细胞的染色更强烈。染色也被认为是在心室肌,在平滑肌的前列腺,回肠,结肠和gallblades.Discussion:染色的组织和亚细胞分布是一致的,它是由于结合抗体的人β(3)-肾上腺素受体。人类白色脂肪细胞中β(3)-肾上腺素受体的存在与其可以介导人类白色脂肪细胞中脂肪分解的证据一致。在接受咖啡因和麻黄碱治疗的肥胖受试者中,β(3)-肾上腺素受体表达增加,这支持β(3)-肾上腺素受体激动剂在治疗肥胖和2型糖尿病中的潜力。其在心室肌中的表达与β 3肾上腺素受体在该组织中介导负性肌力作用的证据一致。
OBJECTIVES: To investigate whether the beta(3)-adrenoceptor could be identified by immunohistochemistry in intact human white and brown adipocytes and other human tissues, and to investigate the influence of obesity and its treatment with ephedrine and caffeine on the expression of the beta(3)-adrenoceptor in adipocytes.METHODS: Morbidly obese patients were given a hypoenergetic diet (70% of energy expenditure) and some were also treated with ephedrine and caffeine (20/200 mg, three times daily) for 4 weeks. Adipose tissue and other tissues were taken during surgery. Immunohistochemistry was carried out using a monoclonal antibody raised against the human beta(3)-adrenoceptor.RESULTS: Staining was localized to the periphery of cells. All white adipocytes were stained. Those from lean subjects and obese subjects treated with ephedrine and caffeine showed more intense staining than those from untreated obese subjects. Staining was more intense in brown than in white adipocytes in perirenal adipose tissue from phaeochromocytoma patients. Staining was also seen in ventricular myocardium, and in smooth muscle of the prostate, ileum, colon and gall bladder.DISCUSSION: The tissue and subcellular distribution of staining was consistent with it being due to binding of the antibody to the human beta(3)-adrenoceptor. The presence of the beta(3)-adrenoceptor in human white adipocytes is consistent with evidence that it can mediate lipolysis in human white adipocytes. The increased expression of the beta(3)-adrenoceptor in obese subjects treated with caffeine and ephedrine supports the potential of beta(3)-adrenoceptor agonists in the treatment of obesity and type 2 diabetes. Its expression in ventricular myocardium is consistent with evidence that the beta(3)-adrenoceptor mediates a negative inotropic effect in this tissue.