The dual-edged role of SIRT1 in energy metabolism and cardiovascular disease

Regulation of energy metabolism is pivotal in the development of cardiovascular diseases. Dysregulation in mitochondrial fatty acid oxidation (FAO) has been linked to cardiac lipid accumulation and diabetic cardiomyopathy. Sirtuin 1 (SIRT1) is a deacetylase that regulates the acetylation of various proteins involved in mitochondrial energy metabolism. SIRT1 mediates energy metabolism by directly and indirectly affecting multiple aspects of mitochondrial processes, such as mitochondrial biogenesis. SIRT1 interacts with essential mitochondrial energy regulators such as Peroxisome Proliferator-Activated Receptor α (PPARα), PPARgcoactivator-1 (PGC1α), Estrogen-Related Receptor α (ERRα), and their downstream targets. Apart from that, SIRT1 regulates additional proteins, including Forkhead Box Protein O1 (FOXO1) and AMP-Activated Protein Kinase (AMPK) in cardiac disease. Interestingly, studies have also shown that the expression of SIRT1 plays a dual-edged role in energy metabolism. Depending on the physiological state, SIRT1 expression can be detrimental or protective. This review focuses on the molecular pathways through which SIRT1 regulates energy metabolism in cardiovascular diseases. We will review SIRT1 and discuss its role in cardiac energy metabolism and its benefits and detrimental effects in heart disease.