Abstract
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that bind to DNA and regulate transcription of genes involved in lipid and glucose metabolism. A growing number of studies provide strong evidence that PPARs are the promising pharmacological targets for therapeutic intervention in various diseases including cardiovascular disorders caused by compromised energy metabolism. PPAR agonists have been widely used for decades as lipid-lowering and anti-inflammatory drugs. Existing studies are mainly focused on the anti-atherosclerotic effects of PPAR agonists; however, their role in the maintenance of cellular bioenergetics remains unclear. Recent studies on animal models and patients suggest that PPAR agonists can normalize lipid metabolism by stimulating fatty acid oxidation. These studies indicate the importance of elucidation of PPAR agonists as potential pharmacological agents for protection of the heart from energy deprivation. Here, we summarize and provide a comprehensive analysis of previous studies on the role of PPARs in the heart under normal and pathological conditions. In addition, the review discusses the PPARs as a therapeutic target and the beneficial effects of PPAR agonists, particularly bezafibrate, to attenuate cardiomyopathy and heart failure in patients and animal models.
Highlights
Peroxisome proliferator-activated receptors (PPARs) play an important role in the regulation of carbohydrate and lipid metabolism in the cell
PPARα is highly expressed in cardiomyocytes, and genetic studies demonstrated the importance of PPARα in fatty acid metabolism in the heart [26,27]
Differential transcriptomic analysis of hearts demonstrated that treatment with a low dose (0.05%) of BF resulted in robust activation of genes involved in a wide-spectrum of biological processes that included metabolism of fatty acids, ketone bodies, amino acids and glucose, metabolism of proteins, mitochondrial protein transport, RNA metabolism, gene expression, DNA repair, chromatin organization, immune system, and organelle biogenesis and maintenance [102]
Summary
Peroxisome proliferator-activated receptors (PPARs) play an important role in the regulation of carbohydrate and lipid metabolism in the cell. PPARs are members of the nuclear hormone receptor superfamily and act as ligand-activated transcription factors They were first discovered in the early 1990s as transcription factors that mediate proliferation of peroxisomes in the cell [1,2,3]. Ligand binding releases the corepressor from the complex and allows activation of coactivator leading to changes in target gene expression [9]. This study revealed that interactions of PPARγ with its binding partners are highly ligand- and DNA-dependent. PPARs represent attractive molecular targets for the development of pharmacological agents and treatment of metabolic disorders, including obesity, type 2 diabetes, dyslipidemia, and cardiovascular diseases
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