Peroxisome proliferator-activated receptor 伪 (PPAR伪) is a ligand-activated transcription factor that regulates the expression of the genes involved in fatty acid oxidation. PPAR伪 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伪 by luciferase reporter assays using GAL4/PPAR伪 chimeric and full-length PPAR伪 systems. Treatment with bixin and norbixin induced the mRNA expression of PPAR伪 target genes involved in fatty acid oxidation in PPAR伪-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伪 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伪, and bixin treatment is useful for the management of obesity-induced metabolic dysfunctions in mice.
Keywords:
bixin; energy metabolism; hepatocyte; norbixin; PPAR伪