运动增强选择性β3-肾上腺素能受体激动剂BRL 35135对肥胖Zucker大鼠的抗肥胖作用。

Potentiation of the anti-obesity effect of the selective beta 3-adrenoceptor agonist BRL 35135 in obese Zucker rats by exercise.

作者信息

Santti E, Huupponen R, Rouru J, Hänninen V, Pesonen U, Jhanwar-Uniyal M, Koulu M

机构信息

Department of Pharmacology, University of Turku, Finland.

出版信息

Br J Pharmacol. 1994 Dec;113(4):1231-6. doi: 10.1111/j.1476-5381.1994.tb17129.x.

DOI:10.1111/j.1476-5381.1994.tb17129.x

PMID:7889277

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1510474/

Abstract

UNLABELLED

The effects of chronic treatments with a selective beta 3-adrenoceptor agonist and a selective alpha 2-adrenoceptor antagonist and their interactions with physical exercise training were studied in experimental obesity. 2. BRL 35135 (beta 3-agonist, 0.5 mg kg-1 day-1 p.o.), atipamezole (alpha 2-antagonist, 4.0 mg kg-1 day-1 p.o.) and placebo were given to genetically obese male Zucker rats. Half of the rats were kept sedentary whereas the other half were subjected to moderate treadmill exercise training. Body weight gain, cumulative food intake, the neuropeptide Y content of the hypothalamic paraventricular nucleus, brown adipose tissue thermogenic activity (measured as GDP binding), plasma insulin and glucose levels were measured after 3 weeks' treatment and exercise. 3. Treatment with BRL 35135 reduced weight gain by 19%, increased brown adipose tissue thermogenic activity 45-fold and reduced plasma insulin by 50%. Atipamezole slightly increased food intake and neuropeptide Y content in the paraventricular hypothalamic nucleus but had no effect on the other measured parameters. Exercise alone had no effect on weight gain, food intake or thermogenic activity, whereas it reduced plasma insulin and glucose levels. 4. The effect of BRL 35135 on weight gain and thermogenic activity was significantly potentiated by exercise; the reduction in weight gain was 56% in comparison with 19% in sedentary animals. Food intake was significantly reduced in the BRL 35135-treated-exercise-trained animals, although neither beta 3-agonist nor exercise alone affected it. 5. Based on the present results in genetically obese Zucker rats, combination of 03-agonist treatment with a moderate physical training may offer a new feasible approach to the therapy of obesity.-

KEYWORDS

BRL 35135; atipamezole; P3-adrenoceptor agonism; M2-adrenoceptor antagonism; brown adipose tissue; thermogenesis;genetic obesity; Zucker rat; exercise; neuropeptide Y

摘要

未标记

在实验性肥胖中研究了选择性β3-肾上腺素能受体激动剂和选择性α2-肾上腺素能受体拮抗剂的长期治疗效果及其与体育锻炼训练的相互作用。2. 给遗传性肥胖雄性 Zucker 大鼠给予 BRL 35135（β3-激动剂，0.5 毫克/千克/天，口服）、阿替美唑（α2-拮抗剂，4.0 毫克/千克/天，口服）和安慰剂。一半大鼠保持久坐不动，而另一半进行中等强度的跑步机运动训练。在 3 周的治疗和运动后，测量体重增加、累积食物摄入量、下丘脑室旁核的神经肽 Y 含量、棕色脂肪组织产热活性（以 GDP 结合量衡量）、血浆胰岛素和葡萄糖水平。3. 用 BRL 35135 治疗使体重增加减少 19%，棕色脂肪组织产热活性增加 45 倍，血浆胰岛素降低 50%。阿替美唑略微增加了下丘脑室旁核中的食物摄入量和神经肽 Y 含量，但对其他测量参数没有影响。单独运动对体重增加、食物摄入量或产热活性没有影响，而它降低了血浆胰岛素和葡萄糖水平。4. 运动显著增强了 BRL 35135 对体重增加和产热活性的影响；与久坐动物的 19%相比，体重增加减少了 56%。在接受 BRL 35135 治疗并进行运动训练的动物中，食物摄入量显著减少，尽管单独使用β3-激动剂或运动均未对其产生影响。5. 根据目前在遗传性肥胖 Zucker 大鼠中的结果，β3-激动剂治疗与适度体育训练相结合可能为肥胖治疗提供一种新的可行方法。