Abstract
Agonists directed against the α and γ isoforms of the peroxisome proliferator-activated receptors (PPARs) have become important for the respective treatment of hypertriglyceridemia and insulin resistance associated with metabolic disease. PPARδ is the least well characterized of the three PPAR isoforms. Skeletal muscle insulin resistance is a primary risk factor for the development of type 2 diabetes. There is increasing evidence that PPARδ is an important regulator of skeletal muscle metabolism, in particular, muscle lipid oxidation, highlighting the potential utility of this isoform as a drug target. In addition, PPARδ seems to be a key regulator of skeletal muscle fiber type and a possible mediator of the adaptations noted in skeletal muscle in response to exercise. In this review we summarize the current status regarding the regulation, and the metabolic effects, of PPARδ in skeletal muscle.
- AMPK, AMP-activated protein kinase
- bezafibrate, 2-(4-{2-[(4-chlorobenzoyl)amino]ethyl}phenoxy)-2-methylpropanoic acid
- BMI, body mass index
- clofibrate, ethyl 2-(4-chlorophenoxy)-2-methylpropanoate
- FABP, fatty acid-binding protein
- fenofibrate, propan-2-yl 2-{4-[(4-chlorophenyl)carbonyl]phenoxy}-2-methylpropanoate
- gemfibrozil, 5-(2,5-dimethylphenoxy)-2,2-dimethyl-pentanoic acid
- GW0742, 4-[2-(3-fluoro-4-trifluoromethyl-phenyl)-4-methyl-thiazol-5-ylmethylsulfanyl]-2-methyl-phenoxy}-acetic acid
- GW501516, 2-[2-methyl-4-([4-methyl-2-[4-(trifluoromethyl)phenyl)-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid
- GW610742X, 3-(4-(3-(4-chloro-2-phenoxyphenoxy)butoxy)-2-ethylphenyl)propionic acid
- GWAS, genome-wide association studies
- HDL, high-density lipoprotein
- L-165041, [4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid
- LBD, ligand-binding domain
- MAFbx, muscle atrophy F-box
- MBX-8025, {2-methyl-4-[5-methyl-2-(4-trifluoromethyl-phenyl)-2H-[12,3]triazol-4-ylmethylsulfanyl]-phenoxy}-acetic acid
- MHC, myosin heavy chain
- MuRF1, muscle ring finger 1
- PDC, pyruvate dehydrogenase complex
- PDK, pyruvate dehydrogenase kinase
- PGC1α, PPARγ coactivator 1α
- PPAR, peroxisome proliferator-activated receptors
- PPRE, peroxisomal proliferator response element
- RA, retinoic acid
- RXR, retinoid X receptor
- SMRT, silencing mediator for retinoic acid and thyroid hormone receptor
- SNP, single-nucleotide polymorphism
- © 2009 by The American Society for Pharmacology and Experimental Therapeutics
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