Protective effect of fasting in hearts and arteries of Pparα −/− mice

Peroxisome proliferator activated receptors (PPARs), of which there are three subtypes, are important determinants of cardiovascular health. Generally, following stimulation by fatty acids, PPARs alter the expression of metabolic genes that regulate energy homeostasis. In the present study, we examined the effect of fasting on cardiac and vascular function in wild‐type (WT) and PPARα‐deficient ( Ppar α −/− ) mice. In isolated aortas from mice fed normal chow, relaxation to acetylcholine (ACh), but not sodium nitroprusside, was impaired by 25% in Ppar α −/− mice. Additionally, we found that eNOS mRNA expression was reduced 2.4‐fold in aortas of fed Ppar α −/− mice. Interestingly, fasting for 36 hours restored relaxation to ACh in Ppar α −/− mice without altering the response in WT mice. Ex vivo cardiac contractility demonstrated that hearts from fed Ppar α −/− mice were 37% weaker than WT hearts. Similar to the aorta, fasting for 36 hours improved cardiac contractility by 46% in Ppar α −/− mice. Thus, fasting improves endothelial function and cardiac contractility in Ppar α −/− mice, suggesting that PPARα is normally protective in the cardiovascular system. This work was supported by AHA SDGs 0735053N (Dr. Andresen), 11SDG5330016 (Dr. Wacker), AHA Postdoctoral grant 7650044 (Dr. Silswal), and a NIH‐NIAMS grant RC2 AR058962 (Drs. Andresen and Wacker).