复旦团队:生酮饮食对心脏健康有什么负面影响?
  • 生酮饮食(KD)、频繁深度禁食或外源β-羟丁酸(β-OHB,一种组蛋白脱乙酰酶2抑制剂)可降低大鼠线粒体生物合成,减少细胞呼吸,增加心肌细胞凋亡和纤维化;
  • 机制上,酮体β-OHB水平的增加,能促进Sirt7启动子的组蛋白乙酰化,并可激活Sirt7转录,反过来又能抑制线粒体核糖体编码基因的转录和线粒体生物合成,导致心肌细胞凋亡和纤维化;
  • 人房颤心脏组织中β-OHB水平和SIRT7表达升高,线粒体生物合成降低,心肌纤维化增加。
主编推荐语
nana
生酮饮食(KD) 已广泛用于临床多种相关疾病治疗,同时,越来越多的健康人为了预防肥胖也选择KD。Signal Transduction and Targeted Therapy近期发表的复旦大学赵健元团队的研究,通过体外培养细胞、动物模型和临床样本分析,发现长时间KD暴露和β-OHB积累可诱导心肌纤维化,影响健康。本研究结果提示,除非KD对心脏系统的不良影响可以有效避免,否则健康人选择使用KD来减肥应慎重考虑。
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Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis

生酮饮食抑制线粒体生物合成并诱导心脏纤维化

10.1038/s41392-020-00411-4

02-09, Article

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In addition to their use in relieving the symptoms of various diseases, ketogenic diets (KDs) have also been adopted by healthy individuals to prevent being overweight. Herein, we reported that prolonged KD exposure induced cardiac fibrosis. In rats, KD or frequent deep fasting decreased mitochondrial biogenesis, reduced cell respiration, and increased cardiomyocyte apoptosis and cardiac fibrosis. Mechanistically, increased levels of the ketone body β-hydroxybutyrate (β-OHB), an HDAC2 inhibitor, promoted histone acetylation of the Sirt7 promoter and activated Sirt7 transcription. This in turn inhibited the transcription of mitochondrial ribosome-encoding genes and mitochondrial biogenesis, leading to cardiomyocyte apoptosis and cardiac fibrosis. Exogenous β-OHB administration mimicked the effects of a KD in rats. Notably, increased β-OHB levels and SIRT7 expression, decreased mitochondrial biogenesis, and increased cardiac fibrosis were detected in human atrial fibrillation heart tissues. Our results highlighted the unknown detrimental effects of KDs and provided insights into strategies for preventing cardiac fibrosis in patients for whom KDs are medically necessary.

First Authors:
Sha Xu,Hui Tao,Wei Cao

Correspondence Authors:
Jian-Yuan Zhao

All Authors:
Sha Xu,Hui Tao,Wei Cao,Li Cao,Yan Lin,Shi-Min Zhao,Wei Xu,Jing Cao,Jian-Yuan Zhao

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