Bixin Activates PPARα and Improves Obesity-Induced Abnormalities of Carbohydrate and Lipid Metabolism in Mice

Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a ligand-activated transcription factor that regulates the expression of the genes involved in fatty acid oxidation. PPAR alpha activators induce fatty acid oxidation in the liver, thereby improving lipid and carbohydrate metabolism in obese mice. In this study, the dietary cis-carotenoids bixin and norbixin, which are commonly used in the food coloring industry, were found to activate PPAR alpha by luciferase reporter assays using GAL4/PPAR alpha chimeric and full-length PPAR alpha systems. Treatment with bixin and norbixin induced the mRNA expression of PPAR alpha target genes involved in fatty acid oxidation in PPAR alpha-expressing HepG2 hepatocytes. In obese KK-Ay mice, bixin treatment suppressed the development of hyperlipidemia and hepatic lipid accumulation. In the livers of bixin-treated mice, the mRNA levels of PPAR alpha target genes related to fatty acid oxidation were up-regulated. Moreover, bixin treatment also improved obesity-induced dysfunctions of carbohydrate metabolism, such as hyperglycemia, hyperinsulinemia, and hypoadiponectinemia. Glucose tolerance test and insulin tolerance test revealed that glucose intolerance and insulin resistance in KK-Ay obese mice were attenuated by the treatment with bixin. These results indicate that bixin acts as a food-derived agonist of PPAR alpha, and bixin treatment is useful for the management of obesity-induced metabolic dysfunctions in mice.