The role of PPARalpha in lipid metabolism and obesity: focusing on the effects of estrogen on PPARalpha actions.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor that belongs to the steroid hormone receptor superfamily. PPARalpha is expressed predominantly in tissues that have a high level of fatty acid catabolism, such as liver, heart, and muscle. PPARalpha regulates the expression of a number of genes critical for lipid and lipoprotein metabolism. PPARalpha ligand fibrates have been used for the treatment of dyslipidemia due to their ability to lower plasma triglyceride levels and elevate HDL cholesterol levels. PPARalpha activators have been shown to regulate obesity in rodents by both increasing hepatic fatty acid oxidation and decreasing the levels of circulating triglycerides responsible for adipose cell hypertrophy and hyperplasia. However, these effects of PPARalpha on obesity and lipid metabolism may be exerted with sexual dimorphism and seem to be influenced by estrogen. Estrogen inhibits the actions of PPARalpha on obesity and lipid metabolism through its effects on PPARalpha-dependent regulation of target genes. Thus, the use of fibrates seems to be effective in men and postmenopausal women with obesity and lipid disorders, but not in premenopausal women with functioning ovaries.