PPARδ: Burning off the Fat

Energy consumption and fat metabolism are the keys to controlling weight gain. Peroxisome proliferator-activated receptors (PPARs) are essential regulators of lipid storage and metabolism. The three isoforms of PPARs--PPARα, PPARγ, PPARδ--exhibit tissue-specific expression and functions. PPARγ stimulates adipogenesis and lipid storage, whereas PPARα stimulates lipid combustion in the liver. The role of PPARδ had not been determined. Wang et al. used transgenic mice overexpressing PPARδ in adipose tissue to show that PPARδ inhibited weight gain and blocked fat storage. In adipose tissue from the transgenic mice, PPARδ promoted expression of β oxidation enzymes, triglyceride hydrolysis enzymes involved in lipid metabolism, and of proteins that uncouple mitochondria, which allows cellular energy stores to be converted to heat (thermogenesis). In cultured cells overexpressing PPARδ, β-oxidation and triglyceride metabolism were increased in response to a PPARδ agonist. The effects of PPARδ were very similar to those of the transcriptional coactivator PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) and in cultured cells or gastrocnemius muscle. PPARδ and PGC-1α coprecipitated, which suggested that the thermogenic effects of PGC-1α may be mediated through interaction with PPARδ. PPARδ agonists may provide yet another target in the war against obesity. Y.-X. Wang, C.-H. Lee, S. Tiep, R. T. Yu, J. Ham, H. Kang, R. M. Evans, Peroxisome-proliferator-activated receptor δ activates fat metabolism to prevent obesity. Cell 113, 159-170 (2003). [Online Journal]