Peroxisome proliferator-activated receptor δ (PPARδ), a novel target site for drug discovery in metabolic syndrome |
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Authors: | Sadao Takahashi Toshiya Tanaka Tatsuhiko Kodama Juro Sakai |
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Affiliation: | aThird Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-0063, Japan;bLaboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Komaba 153-8904, Japan;cExploratory Research for Advanced Technology of Japan Science and Technology Corporation, Aomi 153-0064, Japan |
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Abstract: | The development of new treatments for metabolic syndrome is urgent project for decreasing the prevalence of coronary heart disease and diabetes mellitus in the advanced countries. Peroxisome proliferator-activated receptor (PPAR)α and γ agonists have shed light on the treatment of hypertriglyceridemia and type 2 diabetes mellitus, respectively. Among PPARs, analysis of the PPARδ functions is lagging behind because specific PPARδ agonists have not been developed. The appearance of new PPARδ agonists is brightening the prospects for elucidating the physiological role of PPARδ. PPARδ is a new target for the treatment of metabolic syndrome. In particular, the fact that fatty acid oxidation and energy dissipation in skeletal muscle and adipose tissue by PPARδ agonists lead to improved lipid profile, reduced adiposity and insulin sensitivity is a breakthrough. It seems that treatment of PPARδ agonists operate similarly to the caloric restriction and prolonged exercise. We suggest that the physiological role of PPARδ may be an indicator for switching from glucose metabolism to fatty acid metabolism. To receive new benefits of PPARδ agonists against metabolic syndrome by increasing fatty acid consumption in skeletal muscle and adipose tissue, we need to unveil more details on the functions of PPARδ itself and its agonists in the future. |
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Keywords: | PPARδ Metabolic syndrome Fatty acids oxidation Adaptive thermogenesis |
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