Davis Lisa M, Michaelides Michael, Cheskin Lawrence J, Moran Timothy H, Aja Susan, Watkins Paul A, Pei Zhengtong, Contoreggi Carlo, McCullough Karen, Hope Bruce, Wang Gene Jack, Volkow Nora D, Thanos Panayotis K
Department of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Neuroendocrinology. 2009;89(2):152-62. doi: 10.1159/000170586. Epub 2008 Nov 4.
The dopamine (DA) D(2) receptor (D2R) agonist bromocriptine (BC) decreases body fat in animal and human models and increases lean muscle mass, improves glucose intolerance and insulin resistance, and reduces triglycerides and free fatty acids. We have previously shown a negative correlation between D2R and body weight in obese individuals and in rodents, and that chronic food restriction increases D2R binding in genetically obese rats. The purpose of this study was to assess whether the antiobesity and metabolic effects of BC are related to changes in midbrain DA and D2R activity by measuring D2R and DA transporter (DAT) binding in a genetic (leptin-receptor-deficient) and environmental (diet-induced) rodent obesity model.
Obese (fa/fa) (leptin-receptor-deficient), lean (FA/FA) Zucker rats and rats with diet-induced obesity (DIO) were treated with 10 mg/kg BC for 4 weeks. Body weight, food intake, locomotor activity and blood glucose levels were measured along with D2R- and DAT-binding levels using in vitro receptor autoradiography.
BC decreased food intake and body fat and increased locomotor activity in both the (fa/fa) and DIO rats. Furthermore, BC increased D2R binding in (fa/fa) but not in DIO rats. Finally, BC increased DAT binding in DIO rats but not in the (fa/fa) rats.
These observations are all consistent with the existence of unique leptin-DA interactions and the hypothesis that there is hyposensitivity of the DA system in obesity.
多巴胺（DA）D2受体（D2R）激动剂溴隐亭（BC）可降低动物和人体模型中的体脂，增加瘦肌肉量，改善葡萄糖耐量和胰岛素抵抗，并降低甘油三酯和游离脂肪酸水平。我们之前已经表明，肥胖个体和啮齿动物体内D2R与体重呈负相关，并且长期食物限制会增加遗传性肥胖大鼠的D2R结合。本研究的目的是通过测量基因（瘦素受体缺陷）和环境（饮食诱导）啮齿动物肥胖模型中的D2R和多巴胺转运体（DAT）结合，评估BC的抗肥胖和代谢作用是否与中脑DA和D2R活性的变化有关。
将肥胖（fa/fa）（瘦素受体缺陷）、瘦（FA/FA）的 Zucker 大鼠以及饮食诱导肥胖（DIO）大鼠用 10 mg/kg BC 治疗 4 周。使用体外受体放射自显影法测量体重、食物摄入量、运动活性和血糖水平以及 D2R 和 DAT 的结合水平。
BC 降低了（fa/fa）大鼠和 DIO 大鼠的食物摄入量和体脂，并增加了它们的运动活性。此外，BC 增加了（fa/fa）大鼠的 D2R 结合，但未增加 DIO 大鼠的。最后，BC 增加了 DIO 大鼠的 DAT 结合，但未增加（fa/fa）大鼠的。
这些观察结果均与独特的瘦素-多巴胺相互作用的存在以及肥胖中多巴胺系统存在低敏性的假设一致。
