Kaji Noriyuki, Takagi Yoshiichi, Matsuda Satomi, Takahashi Anna, Fujio Sakurako, Asai Fumitoshi
Laboratory of Veterinary Pharmacology School of Veterinary Medicine Azabu University Kanagawa Japan.
Animal Model Exp Med. 2020 Mar 16;3(1):62-68. doi: 10.1002/ame2.12106. eCollection 2020 Mar.
Liraglutide, a GLP-1 receptor agonist, has recently been used to treat metabolic syndrome (MS) because of its anti-diabetic and anti-obesity effects. We have previously shown that Wistar Bonn Kobori diabetic and fatty (WBN/Kob-Lepr , WBKDF) rats fed a high-fat diet (HFD) developed MS including marked obesity, hyperglycemia, and dyslipidemia. To obtain further information on WBKDF-HFD rats as a severe MS model, we performed a pharmacological investigation into the anti-MS effects of liraglutide in this model.
Seven-week-old male WBKDF-HFD rats were allocated to three groups (N = 8 in each group): a vehicle group, a low-dose liraglutide group, and a high-dose liraglutide group. They received subcutaneous injections of either saline or liraglutide at doses of 75 or 300 μg/kg body weight once daily for 4 weeks.
Results showed that liraglutide treatment reduced body weight gain and food intake in a dose-dependent manner. The marked hyperglycemia and the glucose tolerance were also significantly ameliorated in the liraglutide-treated groups. Moreover, liraglutide also reduced the plasma triglyceride concentration and liver fat accumulation.
The present study demonstrated that liraglutide could significantly alleviate MS in WBKDF-HFD rats, and the reaction to liraglutide is similar to human patients with MS. WBKDF-HFD rats are therefore considered to be a useful model for research on severe human MS.
利拉鲁肽是一种胰高血糖素样肽-1（GLP-1）受体激动剂，因其具有抗糖尿病和抗肥胖作用，近来被用于治疗代谢综合征（MS）。我们之前已经表明，喂食高脂饮食（HFD）的威斯塔·波恩·小堀糖尿病和肥胖（Wistar Bonn Kobori diabetic and fatty，WBKDF）大鼠会发展出包括明显肥胖、高血糖和血脂异常在内的代谢综合征。为了获取关于WBKDF-HFD大鼠作为严重代谢综合征模型的更多信息，我们对利拉鲁肽在该模型中的抗代谢综合征作用进行了药理学研究。
将7周龄雄性WBKDF-HFD大鼠分为三组（每组N = 8）：溶剂对照组、低剂量利拉鲁肽组和高剂量利拉鲁肽组。它们每天接受一次皮下注射生理盐水或剂量为75或300μg/kg体重的利拉鲁肽，持续4周。
结果显示，利拉鲁肽治疗以剂量依赖的方式减少体重增加和食物摄入量。利拉鲁肽治疗组中明显的高血糖和葡萄糖耐量也得到显著改善。此外，利拉鲁肽还降低了血浆甘油三酯浓度和肝脏脂肪堆积。
本研究表明，利拉鲁肽可显著减轻WBKDF-HFD大鼠的代谢综合征，并且其对利拉鲁肽的反应与患有代谢综合征的人类患者相似。因此，WBKDF-HFD大鼠被认为是研究严重人类代谢综合征的有用模型。
