OBESITY PPAR: 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--PPAR, PPAR, PPAR--exhibit tissue-specific expression and functions. PPAR stimulates adipogenesis and lipid storage, whereas PPAR stimulates lipid combustion in the liver. The role of PPAR had not been determined. Wang et al. used transgenic mice overexpressing PPAR in adipose tissue to show that PPAR inhibited weight gain and blocked fat storage. In adipose tissue from the transgenic mice, PPAR promoted expression of ß 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 PPAR, ß-oxidation and triglyceride metabolism were increased in response to a PPAR agonist. The effects of PPAR were very similar to those of the transcriptional coactivator PGC-1 (peroxisome proliferator-activated receptor gamma coactivator-1) and in cultured cells or gastrocnemius muscle. PPAR and PGC-1 coprecipitated, which suggested that the thermogenic effects of PGC-1 may be mediated through interaction with PPAR. PPAR 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 activates fat metabolism to prevent obesity. Cell 113, 159-170 (2003). [Online Journal]