Short-term but not long-term high fat diet feeding protects against pressure overload-induced heart failure through activation of mitophagy

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.

Automated summary

The study showed that short-term but not long-term HFD feeding protected against pressure overload-induced heart failure through activation of mitophagy, caution should be exercised in the use of dietary fat intake in the treatment of heart failure.