Lipids, lipoproteins, and peroxisome proliferator activated receptor-delta

Am J Cardiol. 2007 Dec 3;100(11 A):n20-4. doi: 10.1016/j.amjcard.2007.08.009.


Peroxisome proliferator activated receptors (PPARs) are nuclear receptors activated by small, lipophilic compounds. Typically resident on nuclear DNA, full activation requires heterodimer formation with retinoid X receptor and ligand binding, leading to modulation in the expression of hundreds of genes. Of the 3 described forms, (PPAR-alpha, PPAR-gamma, and PPAR-delta), PPAR-delta has been the least investigated. Preclinical in vitro data show that activation of PPAR-delta, like PPAR-alpha, results in enhancement of fatty acid oxidation, leading to increased energy production in the form of adenosine triphosphate and of energy uncoupling. Microarray data in preclinical models suggest substantial PPAR-delta expression in skeletal muscle. Exercise, which induces upregulation of PPAR-delta in muscle tissue, leads to an increased requirement for an external or serum derived triacylglycerol energy source. This suggests that upregulation of skeletal muscle PPAR-delta would influence lipoprotein composition, this being the major source of combustible substrate. In the first human study using a PPAR-delta agonist, experimental data obtained with GW 501516 (a highly specific PPAR-delta agonist) suggested that upregulated enzymes critical to fatty acid oxidation in human cells enhanced fatty acid and beta-oxidation in skeletal muscle.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Animals
  • Fatty Acids / metabolism*
  • Humans
  • Lipid Metabolism
  • Lipoproteins / physiology*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology
  • Oxidation-Reduction
  • PPAR delta / physiology*
  • Thiazoles / pharmacology*
  • Up-Regulation


  • Fatty Acids
  • GW 501516
  • Lipoproteins
  • PPAR delta
  • Thiazoles
  • Adenosine Triphosphate