Poster Theater Flash Session
Carotenoids and Retinoids (CARIG)
β-Cryptoxanthin (BCX), a provitamin A carotenoid, is cleaved by carotenoid cleavage enzymes including β-carotene-15, 15’-oxygenase (BCO1) to generate vitamin A, and β-carotene-9’, 10’-oxygenase (BCO2) which yields bioactive apo-carotenoids. Dietary supplementation of BCX can prevent non-alcoholic fatty liver disease (NAFLD), which is the most common chronic liver disease worldwide. This study aimed to investigate whether BCX-mediated protection against NAFLD proceeds through the liver-mesenteric adipose tissue axis depending on the presence or absence of BCO1/BCO2.
Six-week-old male wild type (WT) mice (n=30) and congenic BCO1-/-/BCO2-/- double KO (DKO) mice (n=30) were randomly fed either a high-refined carbohydrate diet (HRCD, 66.5% CHO) or HRCD with BCX (10 mg/kg diet) for 24 weeks.
Results : Hepatic levels of BCX, but not retinol and retinyl palmitate, were significantly (P < 0.001) higher (33-fold) in the DKO mice than in the WT mice. BCX significantly reduced hepatic steatosis and total cholesterol levels in both WT and DKO mice in comparison with their HRCD counterparts (P < 0.01 and P < 0.001, respectively), albeit through different mechanisms. In the liver, BCX significantly (P < 0.05) down-regulated mRNA for cholesterol synthesis genes Hmgcr and Hmgs1 and nuclear bile acid receptor Fxr, and up-regulated cholesterol catabolism gene Cyp7a1 in DKO mice in comparison with their HRCD counterparts. Furthermore, BCX significantly (P < 0.05) up-regulated antioxidant enzymes Sod1 and Cat in DKO mice in comparison with HRCD littermates. In WT mice, BCX significantly (P < 0.05) up-regulated hepatic mRNA for cholesterol efflux gene Abcg5 and nuclear receptor Shp in comparison with their HRCD counterparts. In mesenteric adipose tissue, BCX significantly down-regulated (P < 0.05) the inflammatory cytokine Il6 and up-regulated fatty acid β-oxidation marker Acox1 and Sirt1 in DKO mice but significantly (P < 0.05) suppressed lipogenesis marker Acc1 in WT mice.
The protective effects of dietary BCX against HRCD-induced NAFLD are achieved through different molecular mechanisms in the liver-mesenteric adipose tissue axis and depend on the carotenoid cleavage enzymes.
Funding Sources :
NIFA/AFRI (2017-67017-26363) and USDA/ARS (58-1950-0074)