Obesity is a multifactorial disease, which in turn contributes to the onset of comorbidities, such as diabetes and atherosclerosis. Moreover, there are only few options available for treating obesity, and most current pharmacotherapy causes severe adverse effects, while offering minimal weight loss. Literature shows that metabotropic glutamate receptor 5 (mGluR5) modulates central reward pathways. Herein, we evaluated the effect of VU0409106, a negative allosteric modulator (NAM) of mGluR5 in regulating feeding and obesity parameters. Diet-induced obese C57BL/6 mice were treated for 14 days with VU0409106, and food intake, body weight, inflammatory/hormonal levels, and behavioral tests were performed. Our data suggest reduction of feeding, body weight, and adipose tissue inflammation in mice treated with high-fat diet (HFD) after chronic treatment with VU0409106. Furthermore, a negative modulation of mGluR5 also reduces binge-like eating, the most common type of eating disorder. Altogether, our results pointed out mGluR5 as a potential target for treating obesity, as well as related disorders.

中文翻译：

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代谢型谷氨酸受体 5 型的负调节作为肥胖和暴饮暴食行为的潜在治疗策略。

肥胖是一种多因素疾病，进而导致糖尿病和动脉粥样硬化等合并症的发生。此外，治疗肥胖症的选择很少，而且目前大多数药物疗法都会造成严重的副作用，同时减肥效果却微乎其微。文献表明，代谢型谷氨酸受体 5 (mGluR5) 调节中枢奖赏通路。在此，我们评估了 VU0409106（一种 mGluR5 负变构调节剂 (NAM)）在调节进食和肥胖参数方面的作用。用 VU0409106 治疗饮食诱导的肥胖 C57BL/6 小鼠 14 天，并进行食物摄入、体重、炎症/激素水平和行为测试。我们的数据表明，在长期接受 VU0409106 治疗后，接受高脂肪饮食 (HFD) 治疗的小鼠的进食、体重和脂肪组织炎症均有所减少。此外，mGluR5 的负调节还可以减少暴饮暴食，这是最常见的饮食失调类型。总而言之，我们的结果指出 mGluR5 是治疗肥胖及相关疾病的潜在靶点。