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Title:   Author  item
                                            HUANG, HAIQIU - University Of Marylanditem
                                            XIE, ZHUOHONG - University Of Marylanditem
                                            Yokoyama, Wallace

                                                         - *Wally*item
                                            YU, LIANGLI - University Of Marylanditem
                                            Wang, Thomas

                                                         - *Tom*
  Submitted to: Journal of Nutritional Science
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 1/15/2016
                                    Publication  Date: 3/30/2016
                                    Citation: Huang, H., Xie, Z., Yokoyama, W.H., Yu, L., Wang, T.T. 2016. Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model. Journal of Nutritional Science. doi: 10.1017/jns.2016.3eCollection2016.Interpretive Summary: Cardiovascular disease(CVD)is the No.1 cause of death in the industrialized countries, including the U.S.; and hypercholesterolemia is one of the major risk factors for CVD. Cholestyramine (CA) has been widely used to treat hypercholesterolemia; however, its effects on cholesterol and lipid metabolism are not fully understood at the transcriptional level. The current study identified CYP51 as the key response gene in CA treatment instead of the conventionally focused HMG-CoA reductase. This finding updates our understanding in CA’s mechanism of action, and provides additional molecular target to efficiently reduce hypercholesterolemia. These results provide science-based information for a basic and translational scientist interested in lowering circulating cholesterol and the prevention of CVD using diet or foods.
                                Technical Abstract: Cholestyramine(CA)is a bile acid sequestrant widely used as a cholesterol-lowering drug to treat hypercholesterolemia, one of the major risk factors for cardiovascular disease. Despite the wide use of CA its effect on cholesterol and lipid metabolism at a molecular level and over the long term remains unclear. In this study, male golden Syrian hamsters were fed diets containing 36 kcal% fat with or without 1% CA, or chow for 35 days. Gene expression assay identified CYP51, but not HMG-CoA reductase mRNA expression was significantly increased in CA treated group. CA supplementation inhibited the increases in liver weight, VLDL, LDL, hepatic cholesterol, and bile acids induced by ahigh fat diet. CA significantly increased excretion of bile acids, while cholesterol excretion was unchanged. Cholesterol, bile acids, and lipid metabolism associated gene (LDL receptor, CYP7A1, LXRa, and ABCG5/8) expressions were also significantly altered by CA. The current study aimed to advance the understanding of CA’s effect on cholesterol and lipid metabolism. CYP51 was identified as a key enzyme regulated by CA to be associated with maintenance of plasma cholesterol. Results can be used as a foundation for identifying possible molecular changes and consequences on lipid and cholesterol metabolism when consumed by human.


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