Short-term but not long-term high fat diet feeding protects against pressure overload-induced heart failure through activation of mitophagy
Short-term but not long-term high fat diet feeding protects against pressure overload-induced heart failure through activation of mitophagy
复制标题
短期而非长期高脂肪饮食喂养可通过激活线粒体自噬来预防压力超负荷引起的心力衰竭
DOI：
10.1016/j.lfs.2021.119242
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发表时间：
2021-02-21
期刊：
影响因子：
6.1
通讯作者：
Gao, Feng
中科院分区：
文献类型：
--
作者：
Tan, Yanzhen;Li, Min;Gao, Feng
目的：最近的研究表明，通过给动物喂食高脂饮食（HFD）来提高脂肪酸利用率可以减轻心力衰竭（HF）时的心功能障碍。在这里，我们的目的是检查HFD喂养对心脏功能的时间影响，在小鼠心脏failure.Main方法及其潜在mechanism.Main方法：压力超负荷诱导的HF建立通过横向主动脉缩窄（TAC）手术。手术后，将小鼠喂食正常饮食或HFD 8周或16周。关键发现：HFD喂养在手术后不同时间点对心脏功能产生相反的影响。短期HFD喂养（8周）保护心脏免受压力超负荷，抑制心脏肥大和改善心脏功能，而长期HFD喂养（16周）加重心脏功能障碍的TAC小鼠。短期HFD喂养提高心脏脂肪酸利用率，而长期HFD喂养对TAC小鼠的心脏脂肪酸利用率没有显着影响。具体而言，心脏脂肪酸利用率的增加伴随着线粒体自噬的激活和线粒体功能的改善。棕榈酸治疗（400亩M，2小时）刺激脂肪酸氧化和线粒体自噬新生儿心肌细胞。从机制上讲，脂肪酸利用通过上调帕金刺激线粒体自噬。心脏特异性敲除帕金取消短期HFD喂养对心脏功能的保护作用在TAC mice. Significance：这些结果表明，短期而不是长期的HFD喂养通过激活线粒体自噬保护压力超负荷诱导的心力衰竭，饮食脂肪摄入量应谨慎使用在治疗心力衰竭。
Aims: Recent studies have shown that enhancement of fatty acid utilization through feeding animals a high fat diet (HFD) attenuated cardiac dysfunction in heart failure (HF). Here, we aimed to examine the temporal effects of HFD feeding on cardiac function in mice with heart failure and its underlying mechanism.Main methods: Pressure overload-induced HF was established via transverse aortic constriction (TAC) surgery. After surgery, the mice were fed on either normal diet or HFD for 8 or 16 weeks.Key findings: HFD feeding exerted opposite effects on cardiac function at different time points post-surgery. Shortterm HFD feeding (8 wk) protected the heart against pressure overload, inhibiting cardiac hypertrophy and improving cardiac function, while long-term HFD feeding (16 wk) aggravated cardiac dysfunction in TAC mice. Short-term HFD feeding elevated cardiac fatty acid utilization, while long-term HFD feeding showed no significant effects on cardiac fatty acid utilization in TAC mice. Specifically, an increase in cardiac fatty acid utilization was accompanied with activated mitophagy and improved mitochondrial function. Palmitic acid treatment (400 mu M, 2 h) stimulated fatty acid oxidation and mitophagy in neonatal myocytes. Mechanistically, fatty acid utilization stimulated mitophagy through upregulation of Parkin. Cardiac-specific knockdown of Parkin abolished the protective effects of short-term HFD feeding on cardiac function in TAC mice.Significances: These results suggested that short-term but not long-term HFD feeding protects against pressure overload-induced heart failure through activation of mitophagy, and dietary fat intake should be used with caution in treatment of heart failure.