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Title: Beta-Cryptoxanthin prevents non-alcoholic fatty liver disease through different mechanisms depending on the presence or absence of carotenoid cleavage enzymes

Author
item LIM, JI YE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LIU, CHUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item HU, KANG-QUAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SMITH, DONALD - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item AUSMAN, LYNNE - Tufts University
item WANG, XIANG-DONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Current Developments in Nutrition
Publication Type: Abstract Only
Publication Acceptance Date: 3/1/2019
Publication Date: 6/13/2019
Citation: Lim, J., Liu, C., Hu, K., Smith, D.E., Wu, D., Lamon-Fava, S., Ausman, L.M., Wang, X. 2019. Beta-Cryptoxanthin prevents non-alcoholic fatty liver disease through different mechanisms depending on the presence or absence of carotenoid cleavage enzymes [abstract]. Current Developments in Nutrition. 3(Suppl_1). Abstract No. FS06-03-192. https://doi.org/10.1093/cdn/nzz029.FS06-03-192.
DOI: https://doi.org/10.1093/cdn/nzz029.FS06-03-192

Interpretive Summary:

Technical Abstract: Objectives: Beta-Cryptoxanthin (BCX), a provitamin A carotenoid, is cleaved by carotenoid cleavage enzymes including beta-carotene-15, 15'-oxygenase (BCO1) to generate vitamin A, and beta-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. Methods: 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 beta-oxidation marker Acox1 and Sirt1 in DKO mice but significantly (P < 0.05) suppressed lipogenesis marker Acc1 in WT mice. Conclusions: 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.