减少脂肪细胞谷氨酸酶活性促进能量消耗和代谢健康
Simon Lecoutre1,2, Salwan Maqdasy1, David Rizo-Roca3
1Department of Medicine (Huddinge), Karolinska Institutet, ME Endokrinologi, Karolinska University Hospital Huddinge, Huddinge, Sweden.
Nature metabolism
|July 15, 2024
概括
脂肪细胞中氨酸代谢的改变导致肥胖和胰岛素抵抗. 抑制谷氨酸酶可以增加能量消耗,改善葡萄糖耐受性,提供代谢健康益处.
科学领域:
- 代谢途径 代谢途径
- 肥胖研究的研究.
- 脂肪细胞生物学 脂肪细胞生物学
背景情况:
- 谷氨胺-谷氨酸代谢周期的改变与心脏代谢疾病有关.
- 与肥胖相关的胰岛素抵抗与谷氨胺代谢的变化有关.
研究的目的:
- 在肥胖和胰岛素抵抗的背景下,研究谷氨酸-谷氨酸代谢在白色脂肪细胞中的作用.
- 探索向谷氨酸代谢对代谢健康的治疗潜力.
主要方法:
- 对肥胖个体的血和白脂肪组织中谷氨酸与谷氨酸的比率的分析.
- 测量谷氨酸酶和谷氨酸合成酶mRNA和蛋白质水平在人类白色脂肪细胞.
- 评估新陈代谢参数,基因表达和信号通路,以应对小鼠和人类脂肪细胞中的谷氨酸酶抑制.
- 生成脂肪细胞特异性谷氨胺酶淘汰小鼠.
主要成果:
- 与肥胖相关的胰岛素抵抗的特点是血和白色脂肪组织中的谷氨酸与谷氨酸的比率下降.
- 人类白色脂肪细胞中减少的谷氨酸酶活性促进有氧糖解和线粒体的氧化能力.
- 系统性或脂肪细胞特异性谷氨酸酶抑制激活了 inguinal 脂肪细胞中的热生基因程序.
- 抑制谷氨酸酶会增加能量消耗,并改善小鼠的葡萄糖耐受性,即使是在高脂肪饮食条件下.
结论:
- 白色脂肪细胞的谷氨酸循环是能源消耗和代谢健康的关键决定因素.
- 向脂肪细胞中的谷氨酸酶为肥胖和相关代谢障碍提供了潜在的治疗策略.
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