Peroxisome Proliferator-Activated Receptors and the Heart: Lessons from the Past and Future Directions

Table 2

The natural and synthetic ligands of the PPARs and their physiological roles. Modified from [49, 51].

Properties	PPAR-α	PPAR-β/δ	PPAR-γ
Natural ligands	Unsaturated FA, PG, and LT B4; 8-Hydroxyeicosatetraenoic acid	Unsaturated FA; Carbaprostacyclin; Components of VLDL	Unsaturated FA; 15-Hydroxyeicosatetraenoic acid; 9- and 13-hydroxyoctadecadienoic acid; 15-Hydroxy delta 12,14-PG J2; PG J2
Synthetic ligands	Clofibrate and fenofibrate; Gemfibrozil	GW501516	Rosiglitazone and pioglitazone; Troglitazone and ciglitazone; Farglitazar, S26948, and INT131
Physiological roles	Lipid catabolism and homeostasis (stimulating β-oxidation of fatty acids), increased breakdown of TG and FA, increased cellular FA uptake, reduced TG and FA synyheis, control of inflammatory processes, and vascular integrity mediate the hypolipidemic function of fibrates; Liver: increasing FA oxidation and uptake and increasing apoA-I, apoA-II, and HDL; Vessel: increasing TG, HDL, ABCA1, and apoE and decreasing FFA, VLDL, cytokines, and NF-κB	Dyslipidemia?; Wound healing?; Increasing fat oxidation in skeletal and cardiac muscle responsible for insulin sensitivity and glucose; homeostasis and vascular integrity; Adipocentric action: decreasing cytokines, resistin, fFFA, and NF-κB and increasing ABCA1 and GLUT4; Skeletal muscle: increasing glucose uptake and glycogen synthesis	Glucose homeostasis and lipid storage: differentiation and maturation of adipocytes; Increasing IS and glucose; homeostasis; (it prevents hyperglycemia) and; vascular integrity; Skeletal muscle/liver/adipocyte: increasing FA oxidation, UCP, and HDL and decreasing TG

FA: fatty acid; apo: apolipoprotein, PG: prostaglandin, LT: leukotriene, TG: triglyceride, HDL: high-density lipoprotein, ABCA1: ATP-binding cassette subfamily A member 1, FFA: free fatty acid, VLDL: very low-density lipoprotein, NF-B: nuclear factor kappa-light-chain-enhancer of activated B cells, GLUT4: glucose transporter type 4, and UCP: uncoupling protein.