PPARβ/δ and lipid metabolism in the heart

Cardiac lipid metabolism is the focus of attention due to its involvement in the development of cardiac disorders. Both a reduction and an increase in fatty acid utilization make the heart more prone to the development of lipotoxic cardiac dysfunction. The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR)beta/delta modulates different aspects of cardiac fatty acid metabolism, and targeting this nuclear receptor can improve heart diseases caused by altered fatty acid metabolism. In addition, PPAR beta/delta regulates glucose metabolism, the cardiac levels of endogenous antioxidants, mitochondrial biogenesis, cardiomyocyte apoptosis, the insulin signaling pathway and lipid-induced myocardial inflammatory responses. As a result, PPAR beta/delta ligands can improve cardiac function and ameliorate the pathological progression of cardiac hypertrophy, heart failure, cardiac oxidative damage, ischemia reperfusion injury, lipotoxic cardiac dysfunction and lipid -induced cardiac inflammation. Most of these findings have been observed in preclinical studies and it remains to be established to what extent these intriguing observations can be translated into clinical practice. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. (C) 2016 Elsevier B.V. All rights reserved.