Article

PPARδ as a therapeutic target in metabolic disease

Department of Genetics and Complex Diseases, Harvard University School of Public Health, 665 Huntington Avenue, Bldg 2, Room 119, Boston, MA 02115-5818, USA.
FEBS Letters (Impact Factor: 3.34). 02/2008; 582(1):26-31. DOI: 10.1016/j.febslet.2007.11.040
Source: PubMed

ABSTRACT PPAR delta is the only member in the PPAR subfamily of nuclear receptors that is not a target of current drugs. Animal studies demonstrate PPAR delta activation exerts many favorable effects, including reducing weight gain, increasing skeletal muscle metabolic rate and endurance, improving insulin sensitivity and cardiovascular function and suppressing atherogenic inflammation. These activities stem largely from the ability of PPAR delta to control energy balance, reduce fat burden and protect against lipotoxicity caused by ectopic lipid deposition. Therefore, PPAR delta represents a novel therapeutic target and the development of PPAR delta gonists/modulators may be useful for treating the whole spectrum of metabolic syndrome.

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Available from: Chih-Hao Lee, Jun 23, 2014
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    • "metabolism and glucose homeostasis (Braissant et al., 1996; Wang et al., 2003). PPARβ has been shown to increase fat oxidation and reduce lipid accumulation in adipose tissue and in other tissues (Reilly and Lee, 2008). Furthermore, studies in rodents have shown that activation of PPAR-β reduces body weight, increases metabolic rate and improves insulin sensitivity, through increased skeletal muscle fatty acid oxidation (Wang et al., 2003). "
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    • "Several synthetic ligands have also been developed, to improve symptoms of metabolic disorders [122] [123]. Experimental data support that the combined hepatic and muscular effects of PPARβ/δ constitute a " fatty acid futile cycle, " resulting in improved glucose and lipid metabolism [124]. "
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    • "PGC-1α also regulates genes involved in oxidative metabolism and mitochondrial biogenesis by activating transcription factors (Lin et al., 2005), including PPARs. The PPAR nuclear receptor (NR) family consists of PPARα, PPARδ (also called PPARβ) and PPARγ, all of which are drug targets for components of metabolic syndrome (Lee et al., 2003; Reilly and Lee, 2008). PPARα and PPARγ exhibit more restricted effects on fatty acid β-oxidation and fat storage in the liver and adipocyte, respectively. "
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