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, and 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 is unclear.
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, of triglyceride hydrolysis enzymes involved in lipid metabolism, and of proteins that uncouple mitochondria, allowing cellular energy stores to be converted to heat in a process known as 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. In addition, PPARδ and PGC-1α could be coprecipitated, suggesting that the thermogenic effects of PGC-1α may be mediated through interaction with PPARδ. Thus, PPARδ agonists may provide another target in the war against obesity.—NG
Cell 113, 159 (2003).