线粒体TNAP通过脂蛋白的水解控制热生成
Yizhi Sun1,2, Janane F Rahbani3,4, Mark P Jedrychowski1,2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nature
|May 13, 2021
概括
组织非特异性酸 (TNAP) 驱动热生成脂肪细胞中徒劳的肌酸循环,产生热量以对抗肥胖和糖尿病. 这一发现突出了TNAP
科学领域:
- 代谢过程
- 细胞生物学
- 内分泌学
背景情况:
- 适应性热生成会增加能量消耗, 有可能对抗肥胖和糖尿病.
- 以前建议热生成脂肪细胞使用肌酸进行无效的基质循环,产生热量.
- 这一过程所涉及的分子基础和特定酶仍然不清楚.
研究的目的:
- 阐明热生成脂肪细胞中无用的肌酸循环的分子机制.
- 在这些细胞中识别负责脂蛋白水解的酶.
- 研究这种途径在调节能量消耗和体重方面的作用.
主要方法:
- 在小鼠热生成脂肪细胞中研究了脂蛋白酸酶活性.
- 使用生物化学和细胞技术定位了负责这种活动的酶.
- 研究了TNAP抑制对线粒体活性的影响.
- 研究了TNAP在脂肪细胞中的遗传剥离对暴露在寒冷环境中的小鼠能量消耗和体重的影响.
主要成果:
- 已确定非组织特异性酸酶 (TNAP) 是热生成脂肪细胞中的关键酸酶.
- 证明TNAP局部化到这些细胞中的线粒体,在那里它启动了徒劳的肌酸循环.
- 显示TNAP表达被冷暴露上调,其抑制消除了徒劳的循环.
- 发现脂肪细胞中TNAP的遗传删除会减少能量消耗并导致小鼠肥胖.
结论:
- TNAP是热生成脂肪细胞中无用的肌酸循环中介的关键酶.
- 这种由TNAP驱动的徒劳循环在适应性热生成和能量稳定中起着重要作用.
- 针对TNAP可能为肥胖和相关代谢障碍提供一种新的治疗策略.
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