New anti-obesity and anti-diabetic druges for dogs activating brown adipose tissue thermogenesis.

用于狗的新型抗肥胖和抗糖尿病药物，可激活棕色脂肪组织生热作用。

• 批准号: 07556117
• 负责人: SAITO Masayuki
• 金额: $ 1.66万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07556117/
• 关键词: Obesity; Brown adipose tissue; Beta-adrenoceptor; Dogs

Obesity is one of the most important risk factors for diabetes and hypertension in the dog, as in man. In this study, to explore an effective pharmacological method for treatment and prevention of obesity in small animal practises, we have examined in dogs anti-obesity effects of an agonist (CL316,243) to beta3-adrenoceptor which activates brown adipose tissue thermogenesis. When CL316,243 was given intravenously to Beagle dogs, plasma free fatty acid level increased promptly and remarakably, indicating a strong lipolytic action of this drug. When the drug was given orally for 5 weeks, body weight and girth length decreased significantly compared with placebo- controls. Biochemical and histological examinations revealed that the adipose tissues of the dogs chronically given the drug had less triglyceride and expressed a specific thermogenic protein (mitochondrial uncoupling protein). These results show that the beta3-adrenocetor agonist has potent lipolytic and thermogenic action and can be used as an anti-obesity drug in the dog.

肥胖是狗和人患糖尿病和高血压的最重要的风险因素之一。在这项研究中，为了探索治疗和预防小动物肥胖的有效药理学方法，我们在狗身上检测了β3-肾上腺素能受体激动剂(CL316,243)的抗肥胖作用，该受体激活棕色脂肪组织产热。给Beagle犬静脉注射CL316,243后，血浆游离脂肪酸水平迅速而显著升高，表明该药具有较强的降脂作用。当口服药物5周时，与安慰剂对照组相比，体重和周长显著减少。生化和组织学检查显示，长期服用该药物的狗的脂肪组织中甘油三酯较少，并表达一种特定的生热蛋白(线粒体解偶联蛋白)。这些结果表明，β3-肾上腺素能受体激动剂具有很强的降脂和生热作用，可作为狗的减肥药物。

项目成果

I. Nagase et al.: "Expression of uncoupling protein in skeletal muscle and white fat of obese mice treated with thermogenic β3-adrenergic agonist." J. Clim. Invest.97. 2898-2904 (1996)

I. Nagase 等人：“用产热 β3-肾上腺素激动剂治疗的肥胖小鼠骨骼肌和白色脂肪中解偶联蛋白的表达”，J. Clim 2898-2904。

H. Nikami et al.: "Expression of beta3-adrenoceptor and stimulation of glucose transport by beta3-agoista in brown adipocyte primary culture" Journal of Biochemistry. 119. 120-125 (1996)

H. Nikami 等人：“棕色脂肪细胞原代培养物中β3-肾上腺素受体的表达和β3-激动剂对葡萄糖转运的刺激”《生物化学杂志》。

H.Nikami, et al.: "Expression of beta3-adrenoceptor and stimulation of glucose transport by b3-agonist in brown adipocyte primary culture." J.Biochem.119. 120-125 (1996)

H.Nikami 等人：“棕色脂肪细胞原代培养物中 β3 肾上腺素受体的表达和 b3 激动剂对葡萄糖转运的刺激。”

K.Tsukazaki, et al.: "Chronic administration of beta-adrenergic agonists can mimic the stimulative effect of cold exposure on protein synthesis in rat brown adipose tissue." J.Biochem. 117. 96-100 (1995)

K.Tsukazaki 等人：“长期服用 β-肾上腺素能激动剂可以模拟寒冷暴露对大鼠棕色脂肪组织蛋白质合成的刺激作用。”