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OtherReview Article

Regulation of Skeletal Muscle Physiology and Metabolism by Peroxisome Proliferator-Activated Receptor δ

Ewa Ehrenborg and Anna Krook
Pharmacological Reviews September 2009, 61 (3) 373-393; DOI: https://doi.org/10.1124/pr.109.001560
Ewa Ehrenborg
Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (E.E.); and Integrative Physiology Group, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (A.K.)
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Anna Krook
Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden (E.E.); and Integrative Physiology Group, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (A.K.)
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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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Pharmacological Reviews: 61 (3)
Pharmacological Reviews
Vol. 61, Issue 3
September 2009
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OtherReview Article

Regulation of Skeletal Muscle Physiology and Metabolism by Peroxisome Proliferator-Activated Receptor δ

Ewa Ehrenborg and Anna Krook
Pharmacological Reviews September 1, 2009, 61 (3) 373-393; DOI: https://doi.org/10.1124/pr.109.001560

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OtherReview Article

Regulation of Skeletal Muscle Physiology and Metabolism by Peroxisome Proliferator-Activated Receptor δ

Ewa Ehrenborg and Anna Krook
Pharmacological Reviews September 1, 2009, 61 (3) 373-393; DOI: https://doi.org/10.1124/pr.109.001560
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  • Article
    • Abstract
    • I. Introduction
    • II. Peroxisome Proliferator-Activated Receptor Family
    • III. Regulation of Skeletal Muscle Metabolic Phenotype and Fiber Types
    • IV. Peroxisome Proliferator-Activated Receptor δ and Metabolic Disease
    • V. Concluding Thoughts
    • Acknowledgments
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