title: Bixin activates PPARα and improves obesity-induced abnormalities of carbohydrate and lipid metabolism in mice.
abstract: Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates the expression of the genes involved in fatty acid oxidation. PPARα 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 PPARα by luciferase reporter assays using GAL4/PPARα chimeric and full-length PPARα systems. Treatment with bixin and norbixin induced the mRNA expression of PPARα target genes involved in fatty acid oxidation in PPARα-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 PPARα 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 PPARα, and bixin treatment is useful for the management of obesity-induced metabolic dysfunctions in mice.
authors.affiliation: Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Sota
authors.initials: S
authors.lastname: Kato
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kusudo
authors.forename: Aki
authors.initials: A
authors.lastname: Taimatsu
authors.forename: Kahori
authors.initials: K
authors.lastname: Egawa
authors.forename: Min-Sook
authors.initials: MS
authors.lastname: Kang
authors.forename: Takuro
authors.initials: T
authors.lastname: Hiramatsu
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Taku
authors.initials: T
authors.lastname: Uemura
authors.forename: Shizuka
authors.initials: S
authors.lastname: Hirai
authors.forename: Misato
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Horio
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000188:drug therapy / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D047493:PPAR alpha; D002338:Carotenoids; C004588:bixin; C099823:norbixin