Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration—probing the role of PPARα

What is it about?

The heart beats continually over the course of a lifetime, pumping oxygen-rich blood to the tissues of the body. To do so, the heart requires a significant amount of energy, which it acquires from fuel molecules, such as fatty acids and glucose, and a substantial amount of oxygen. When oxygen availability is impaired, for example in diseases such as heart failure or in the course of a journey to high altitude, the capacity of the heart to use fatty acids as a fuel declines and energy reserves also fall. Consumption of leafy green vegetables, such as spinach and beetroot, enhances the blood levels of a molecule, nitrate, which increases oxygen flow to tissues including the heart, but also alters how the heart uses that oxygen. For instance, nitrate increases the capacity for fatty acid oxidation and this even happens in low oxygen conditions, however the mechanism is not known. Here, we sought to investigate the role of a protein, peroxisome proliferator activated receptor alpha (PPARα), which acts as a major regulator for fatty acid oxidation in the heart, in part through its influence on the mitochondria - the molecular powerhouses of the cell. We found that suppression of fat metabolism in the heart under low oxygen conditions involves suppression of PPARα. Furthermore, nitrate acts through PPARα to restore fat oxidation under these conditions. Our work highlights the importance of PPARα in regulating heart energy metabolism in response to varying levels of oxygen.

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