增强器调节器MLL4通过限制AMPK介导的燃料催化作用来控制骨肌肉的代谢效率
Likun Yang1,2, Lin Liu1,2, Wen Wang3,4
1State Key Laboratory of Pharmaceutical Biotechnology, Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China.
Nature communications
|November 26, 2025
概括
基因组单甲基转移酶混合系白血病4 (MLL4) 调节肌肉新陈代谢. 在小鼠中减少MLL4可增加能量消耗,并通过激活AMPK信号来改善代谢健康,从而提供潜在的肥胖治疗方法.
科学领域:
- 代谢研究的研究.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 骨肌肉在全身能量平衡中起着至关重要的作用.
- 了解肌肉如何将其转录和代谢程序适应环境因素对于代谢健康至关重要.
- 基因组蛋白修饰是基因表达和细胞适应的关键调节者.
研究的目的:
- 为了研究基因组单甲基转移酶混合系白血病4 (MLL4) 在骨肌肉代谢适应中的作用.
- 阐明MLL4通过AMPK信号传导影响系统代谢的机制.
- 探索针对MLL4或其下游途径对代谢障碍的治疗潜力.
主要方法:
- 在雄性小鼠的骨肌特异性MLL4切除.
- 评估代谢参数,包括体重,葡萄糖平衡和燃料代谢.
- 分析AMPK信号通路的激活和AMP代谢酶的表达.
- 使用Pentostatin对AMP代谢途径的药理抑制.
主要成果:
- 骨肌特异性MLL4缺乏保护雄性小鼠免受饮食诱导的肥胖和改善葡萄糖平衡.
- 在骨肌中,MLL4的耗尽导致AMP激活蛋白激酶 (AMPK) 的明显激活,从而增强了燃料代谢.
- 发现MLL4与肌细胞增强因子2合作,诱导抑制AMPK活性的酶.
- 对AMP代谢途径的药理抑制模仿了MLL4耗尽的代谢益处.
结论:
- 通过AMPK信号传递,MLL4作为骨肌肉代谢和全身能量平衡的关键调节者.
- 准MLL4或AMP代谢途径为肥胖和相关代谢疾病提供了潜在的治疗策略.
- 这些发现揭示了一种新的表观遗传机制,控制肌肉燃料利用和代谢适应.
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