A Phytol-Enriched Diet Activates PPAR- in the Liver and Brown Adipose Tissue to Ameliorate Obesity-Induced Metabolic Abnormalities

ScopePeroxisome proliferator-activated receptor alpha (PPAR-) is a ligand-activated transcription factor that regulates lipid and carbohydrate metabolism. We investigate the effects of naturally occurring PPAR- agonists, phytol, and its metabolite phytanic acid, on obesity-induced metabolic disorders using a mouse model. Methods and resultsA luciferase reporter assay shows that phytanic acid potently activates PPAR- among PPAR subtypes. In high-fat-diet-induced, severely obese mice, a phytol-enriched diet increases phytanic acid levels in the liver and adipose tissue, where PPAR- is abundantly expressed. A phytol-enriched diet ameliorates severe obesity and the related metabolic abnormalities of white adipose tissue. Moreover, the expression of PPAR- target genes in the liver and brown adipose tissue is enhanced by a phytol-enriched diet, suggesting that phytol and phytanic acid activate PPAR- in these organs. We confirm that phytanic acid treatment induced PPAR- target gene expression in both primary hepatocytes and brown adipocytes from wild-type mice, but not in these cells from PPAR--deficient mice. ConclusionA phytol-enriched diet may increase phytanic acid levels in the liver and brown adipocytes, thereby activating PPAR- in these organs and ameliorating obesity-induced metabolic diseases.