Roles of PPARs on regulating myocardial energy and lipid homeostasis.

Myocardial energy and lipid homeostasis is crucial for normal cardiac structure and function. Either shortage of energy or excessive lipid accumulation in the heart leads to cardiac disorders. Peroxisome proliferator-activated receptors (PPARalpha, -beta/delta and -gamma), members of the nuclear receptor transcription factor superfamily, play important roles in regulating lipid metabolic genes. All three PPAR subtypes are expressed in cardiomyocytes. PPARalpha has been shown to control transcriptional expression of key enzymes that are involved in fatty acid (FA) uptake and oxidation, triglyceride synthesis, mitochondrial respiration uncoupling, and glucose metabolism. Similarly, PPARbeta/delta is a transcriptional regulator of FA uptake and oxidation, mitochondrial respiration uncoupling, and glucose metabolism. On the other hand, the role of PPARgamma on transcriptional regulation of FA metabolism in the heart remains obscure. Therefore, both PPARalpha and PPARbeta/delta are important transcriptional regulators of myocardial energy and lipid homeostasis. Moreover, it appears that the heart needs to have two PPAR subtypes with seemingly overlapping functions in maintaining myocardial lipid and energy homeostasis. Further studies on the potential distinctive roles of each PPAR subtype in the heart should provide new therapeutic targets for treating heart disease.