构成性活性受体ADGRA3信号诱导脂肪热生成
Zewei Zhao1, Longyun Hu1, Bigui Song1
1Shenzhen Key Laboratory of Systems Medicine for inflammatory diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, China.
eLife
|December 24, 2024
概括
粘附G蛋白结合受体A3 (ADGRA3) 促进脂肪热生成,并对抗肥胖. 用hesperetin或过度表达激活ADGRA3会诱导脂肪细胞色,以促进代谢健康.
科学领域:
- 代谢研究的研究.
- 肥胖研究的研究.
- 脂肪组织生物学 脂肪组织生物学
背景情况:
- 脂肪热生成对体温和代谢平衡至关重要.
- 贝塔3-上腺受体 (β3-AR) 调解热生成,但具有有限的人类脂肪细胞表达.
- 识别人类脂肪细胞中的新目标是治疗肥胖症的关键.
研究的目的:
- 为了确定G蛋白结合受体 (GPCR) 在人类脂肪细胞中高度表达.
- 为了研究这种GPCR在脂肪热生成中的作用.
- 探索肥胖的潜在治疗策略.
主要方法:
- 在人类脂肪细胞中选高表达的GPCRs.
- 研究粘附G蛋白结合受体A3 (ADGRA3) 通过小鼠中断和过度表达的功能.
- 使用体外模型进行脂肪细胞色.
- 识别潜在的ADGRA3激动剂.
主要成果:
- 在人类脂肪细胞和小鼠棕色脂肪中,ADGRA3的表达很高.
- 在ADGRA3中,ADGRA3 Knockdown会加剧肥胖症,并降低发热标志物.
- 过度表达ADGRA3激活热生成并改善代谢平衡.
- ADGRA3促进了色脂肪细胞的生物发生.
- 赫斯佩雷丁作为ADGRA3激动剂,诱导色和改善胰岛素抵抗.
结论:
- 构成性活性ADGRA3或素激活的ADGRA3通过Gs-PKA-CREB通路诱导脂肪细胞色.
- 在肥胖和代谢障碍方面,ADGRA3和hesperetin是有前途的治疗点.
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