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TAAR1激动剂可以改善血糖控制,减轻体重,调节控制能量平衡和养的神经回路
Nina Dedic1, Lien Wang1, Eva Hajos-Korcsok1
1Sumitomo Pharma America, Inc., Marlborough, MA, USA.
Molecular metabolism
|January 18, 2024
概括
微氨基关联受体1 (TAAR1) 激动剂通过降低体重和改善血糖控制来治疗精神分裂症,没有其他抗精神病药物 (APD) 的代谢副作用. 这些发现表明,在精神分裂症患者的代谢失调方面,一种新的治疗方法.
科学领域:
- 神经科学是一个神经科学.
- 代谢障碍 代谢障碍 代谢障碍
- 药理学 药理学是指药理学的学科.
背景情况:
- 代谢综合征在精神分裂症患者中很常见,通常因抗精神病药物 (APD) 而恶化.
- 微氨基关联受体1 (TAAR1) 激动剂正在研究用于精神分裂症治疗.
- 新出现的证据表明,TAAR1在代谢调节中起作用.
研究的目的:
- 评估TAAR1激动剂,包括乌洛坦,对体重和代谢参数的影响.
- 为了研究TAAR1激动剂对参与养行为的神经回路的影响.
- 评估TAAR1激动剂作为对APD诱导的代谢副作用的潜在治疗方法.
主要方法:
- 在高脂肪饮食 (HFD) 和饮食诱导肥胖症 (DIO) 的动物模型中研究了TAAR1激动剂 (ulotaront,RO5166017,RO5263397).
- 评估对体重,食物摄入量,耐葡萄糖,胃空气和血葡萄糖/胰岛素的影响.
- 利用c-fos表达的全脑成像来分析神经电路调制.
主要成果:
- TAAR1激动剂通过抑制胃排空来改善葡萄糖耐受性.
- 在HFD大鼠中,Ulotaront降低了体重,食物摄入量和肝脏甘油三.
- TAAR1激动剂逆转了奥兰扎诱导的体重增加和调节与食相关的神经回路.
结论:
- 在动物模型中,TAAR1激动剂表现出缺乏代谢负担,可以降低体重并改善血糖控制.
- 机制包括对葡萄糖平衡和胃空化的外围影响,以及对能量平衡的中央调节.
- TAAR1激动剂代表了与精神分裂症治疗相关的代谢失调的有前途的治疗策略.
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