Poster Topical Area: Carotenoids and Retinoids
Poster Board Number: 3
(Background) We have previously reported that a high-refined carbohydrate diet (HRCD) is more likely to contribute to non-alcoholic fatty liver disease (NAFLD) than a high-fat diet with the same caloric content. The HRCD effect is associated with decreased functions of sirtuin 1 (SIRT1). β-Cryptoxanthin (BCX), a provitamin A carotenoid found primarily in red sweet peppers, has been shown to be protective against NAFLD. BCX can be cleaved by β-carotene-15, 15'-oxygenase (BCO1), and β-carotene-9', 10'-oxygenase (BCO2) to produce bioactive metabolites. BCO1/BCO2 polymorphisms have been observed in human and rodents. (Objectives) In this study, we investigated whether the protective effect of BCX against HRCD-induced NAFLD was dependent on, or independent of BCO1/BCO2, and whether the upregulation of SIRT1 was the underlying mechanism of its physiological actions. (Methods) At 6 weeks of age, BCO1/BCO2 double knockout (BCO1/BCO2 DKO) mice and wild type (WT) mice from a C57BL/6J genetic background were randomly assigned to either the HRCD (n=15, 66.5 % of energy as carbohydrate including sucrose and maltodextrin) or the HRCD with BCX (n=15, 10 mg BCX/kg diet) group for 24 weeks. The dose of BCX (paprika extract rich in 11% BCX from OmniActive) was equivalent to that on daily human consumption of 3-4 ounces of a sweet red pepper. (Results) BCX feeding significantly reduced hepatic steatosis score in both WT and BCO1/BCO2 DKO mice compared to their respective HRCD counterparts (P < 0.05). Moreover, BCX feeding significantly reduced hepatic concentrations of triglyceride and total cholesterol levels in BCO1/BCO2 DKO mice, compared to the corresponding HRCD group. These hepatic changes by BCX feeding were related to the significant upregulation of mRNA and protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and SIRT1, downregulation of mRNA levels of the cholesterol biosynthesis marker (HMG-CoAR) and lipogenesis markers (SREBP-1C, ACC, FAS), and increases in mRNA levels of the fatty acid β-oxidation marker (PPARα). (Conclusion) In conclusion, our results provided compelling experimental evidence that BCX has protective effects against HRCD-induced NAFLD potentially by regulating NAMPT/SIRT1 pathway independent of carotenoid cleavage enzymes.
Supported by NIFA/AFRI (2017-67017-26363) and USDA/ARS (58-1950-0074)
Ji Ye Lim
graduate student (Ph.D)
1) Nutrition and Cancer Biology Lab, JM USDA-HNRCA at Tufts University, Boston, MA, USA, and 2) Biochemical and Molecular Nutrition Program, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA