Tan Yanzhen, Li Min, Wu Guiling, Lou Jing, Feng Mengya, Xu Jie, Zhou Jiaheng, Zhang Pengfei, Yang Hongyan, Dong Ling, Li Jia, Zhang Xing, Gao Feng
School of Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, China; Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
School of Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, China.
Life Sci. 2021 May 1;272:119242. doi: 10.1016/j.lfs.2021.119242. Epub 2021 Feb 16.
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.
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.
HFD feeding exerted opposite effects on cardiac function at different time points post-surgery. Short-term 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 μM, 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.
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.
最近的研究表明，通过给动物喂食高脂饮食（HFD）来增强脂肪酸利用可减轻心力衰竭（HF）中的心脏功能障碍。在此，我们旨在研究喂食HFD对心力衰竭小鼠心脏功能的时间效应及其潜在机制。
通过横向主动脉缩窄（TAC）手术建立压力超负荷诱导的HF模型。手术后，将小鼠分别喂食正常饮食或HFD 8周或16周。
喂食HFD在手术后不同时间点对心脏功能产生相反的影响。短期喂食HFD（8周）可保护心脏免受压力超负荷的影响，抑制心脏肥大并改善心脏功能，而长期喂食HFD（16周）则会加重TAC小鼠的心脏功能障碍。短期喂食HFD可提高心脏脂肪酸利用率，而长期喂食HFD对TAC小鼠的心脏脂肪酸利用率无显著影响。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。棕榈酸处理（400μM，2小时）可刺激新生心肌细胞中的脂肪酸氧化和线粒体自噬。机制上，脂肪酸利用通过上调Parkin来刺激线粒体自噬。心脏特异性敲低Parkin可消除短期喂食HFD对TAC小鼠心脏功能的保护作用。
这些结果表明，短期而非长期喂食HFD可通过激活线粒体自噬来预防压力超负荷诱导的心力衰竭，并且在心力衰竭治疗中应谨慎使用饮食脂肪摄入。
