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完整人类脂肪细胞和心室心肌中β(3) - 肾上腺素能受体的免疫组织化学鉴定:肥胖以及麻黄碱和咖啡因治疗的影响

Immunohistochemical identification of the beta(3)-adrenoceptor in intact human adipocytes and ventricular myocardium: effect of obesity and treatment with ephedrine and caffeine.

作者信息

De Matteis R, Arch J R S, Petroni M L, Ferrari D, Cinti S, Stock M J

机构信息

Institute of Normal Human Morphology-Anatomy, University of Ancona, Ancona, Italy.

出版信息

Int J Obes Relat Metab Disord. 2002 Nov;26(11):1442-50. doi: 10.1038/sj.ijo.0802148.

DOI:10.1038/sj.ijo.0802148
PMID:12439645
Abstract

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.

摘要

目的

研究β(3)-肾上腺素能受体能否通过免疫组织化学方法在完整的人白色和棕色脂肪细胞及其他人体组织中被识别,以及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。

方法

病态肥胖患者接受低能量饮食(能量消耗的70%),部分患者还接受麻黄碱和咖啡因(20/200毫克,每日三次)治疗4周。手术期间采集脂肪组织和其他组织。使用针对人β(3)-肾上腺素能受体产生的单克隆抗体进行免疫组织化学检测。

结果

染色定位于细胞周边。所有白色脂肪细胞均被染色。来自瘦人以及接受麻黄碱和咖啡因治疗的肥胖患者的白色脂肪细胞染色比未治疗的肥胖患者的更强烈。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更强烈。在心室心肌以及前列腺、回肠、结肠和胆囊的平滑肌中也可见染色。

讨论

染色的组织和亚细胞分布与抗体与人β(3)-肾上腺素能受体结合一致。人白色脂肪细胞中存在β(3)-肾上腺素能受体与它可介导人白色脂肪细胞脂解的证据相符。用咖啡因和麻黄碱治疗的肥胖患者中β(3)-肾上腺素能受体表达增加支持了β(3)-肾上腺素能受体激动剂在治疗肥胖和2型糖尿病方面的潜力。其在心室心肌中的表达与β(3)-肾上腺素能受体在此组织中介导负性变力作用的证据相符。

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