Bromocriptine administration reduces hyperphagia and adiposity and differentially affects dopamine D2 receptor and transporter binding in leptin-receptor-deficient Zucker rats and rats with diet-induced obesity.
Bromocriptine administration reduces hyperphagia and adiposity and differentially affects dopamine D2 receptor and transporter binding in leptin-receptor-deficient Zucker rats and rats with diet-induced obesity.
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DOI：
10.1159/000170586
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发表时间：
2009
影响因子：
4.1
通讯作者：
Thanos PK
中科院分区：
文献类型：
--
作者：
Davis LM;Michaelides M;Cheskin LJ;Moran TH;Aja S;Watkins PA;Pei Z;Contoreggi C;McCullough K;Hope B;Wang GJ;Volkow ND;Thanos PK
多巴胺（DA）D2受体（D2 R）激动剂溴隐亭（BC）在动物和人类模型中减少体脂，增加瘦肌肉质量，改善葡萄糖耐受不良和胰岛素抵抗，并减少甘油三酯和游离脂肪酸。我们先前已经表明，在肥胖个体和啮齿动物中，D2 R和体重之间存在负相关性，并且慢性食物限制会增加遗传性肥胖大鼠的D2 R结合。本研究的目的是评估BC的减肥和代谢作用是否与中脑DA和D2 R活性的变化有关，通过测量D2 R和DA转运蛋白（DAT）在遗传（瘦素受体缺陷）和环境（饮食诱导）啮齿动物肥胖模型中的结合。用10 mg/kg BC处理肥胖（fa/fa）（瘦素受体缺陷）、瘦（FA/FA）Zucker大鼠和饮食诱导肥胖（DIO）大鼠4周。使用体外受体放射自显影术测量体重、食物摄入、自发活动和血糖水平沿着D2 R和DAT结合水平。BC减少食物摄入量和体脂，并增加自发活动（fa/fa）和DIO大鼠。此外，BC增加D2 R结合（fa/fa），但不是在DIO大鼠。最后，BC增加DIO大鼠的DAT结合，但不增加（fa/fa）大鼠的DAT结合。这些观察结果都与存在独特的瘦素-DA相互作用和肥胖中DA系统低敏感性的假设一致。
The dopamine (DA) D2 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.
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影响因子：
16.2
作者：
Cincotta, AH;Meier, AH
通讯作者：
Meier, AH
影响因子：
4.1
作者：
Bina, KG;Cincotta, AH
通讯作者：
Cincotta, AH
影响因子：
9.8
作者：
CINCOTTA, AH;SCHILLER, BC;MEIER, AH
通讯作者：
MEIER, AH
影响因子：
25.7
作者：
Davis, Lisa M.;Pei, Zhengtong;Moran, Timothy H.
通讯作者：
Moran, Timothy H.
影响因子：
6.1
作者：
Cincotta, AH;Tozzo, E;Scislowski, PWD
通讯作者：
Scislowski, PWD