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Title: Hypocholesterolemic effects of hydroxypropyl methylcellulose are mediated by altered gene expression in hepatic bile and cholesterol pathways of male hamsters

item Bartley, Glenn
item Yokoyama, Wallace - Wally
item YOUNG, SCOTT - Dow Chemical Company
item ANDERSON, KERR - Dow Chemical Company
item HUNG, SHAO-CHING - Dow Chemical Company
item ALBERS, DAVID - Dow Chemical Company
item LANGHORST, MARSHA - Dow Chemical Company
item TUROWSKI, MACIEJ - Dow Chemical Company
item Kim, Hyunsook

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/10/2010
Publication Date: 7/1/2010
Citation: Bartley, G.E., Yokoyama, W.H., Young, S.A., Anderson, K., Hung, S., Albers, D.R., Langhorst, M.L., Turowski, M., Kim, H. 2010. Hypocholesterolemic effects of hydroxypropyl methylcellulose are mediated by altered gene expression in hepatic bile and cholesterol pathways of male hamsters. Journal of Nutrition. 140(7): 1255-1260.

Interpretive Summary: Recently combination of lifestyle changes and appropriately controlled diets has received more attention to reduce cardiovascular disease risk. Hydroxypropyl methylcellulose (HPMC) is a well-characterized semi-synthetic cellulose derivative that has the structural and physiological properties of a soluble non-fermentable dietary fiber. In the present study, HPMC supplemented diets showed significant effects of cholesterol and body weight reduction in hamsters. Furthermore, these dramatic changes were associated with hepatic lipid metabolism-related gene expression. Our data suggested that increased bile acid and sterol excretion with HPMC supplemented diets could trigger dramatic changes in lipid and cholesterol metabolism in liver. This study further supports the potential dietary use of HPMC for the prevention of cardiovascular disease and possibly obesity

Technical Abstract: Hydroxypropyl methylcellulose (HPMC), a semi-synthetic non-fermentable soluble dietary fiber (SDF) modulates plasma lipoprotein profiles and hepatic lipid levels. HPMC is not absorbed by the body but its presence in the intestinal lumen increases fecal fat, sterol, and bile acid excretion and decreases intestinal cholesterol absorption which may result indirectly in changes in hepatic lipid metabolism. To elucidate the underlying mechanism, we measured hepatic expression of genes involved in cholesterol, bile acid, and fatty acid metabolism in hamsters fed 39% fat calorie diets containing either 5% HPMC or 5% insoluble dietary fiber (microcrystalline cellulose, MCC) for 4 weeks. Hamsters fed HPMC gained significantly less body weight without changes in food intake and had significantly lower plasma total-, VLDL-, and LDL-cholesterol and triglyceride concentrations and hepatic lipid levels than animals on MCC diet. Cholesterol-lowering effects of HPMC supplementation were significantly correlated with up-regulation of the expression of hepatic CYP7A1, CYP51, and HMG-CoA reductase genes, indicating both increased cholesterol and bile acid synthesis. Interestingly, regulation of CYP7A1 expression was not dependent of FXR' expression but dependent of HNF-4'. Up-regulation of hepatic LDLR expression was inversely correlated with plasma cholesterol levels. Reductions in plasma and hepatic triglyceride levels were associated with hepatic expression of genes related to fatty acid oxidation (up-regulation) and fatty acid synthesis (down-regulation). Our data suggest that altered hepatic expression of lipid metabolism-related genes, possibly due to modulation of fecal bile acid excretion and intestinal cholesterol absorption, contributes to lipid-lowering effects of HPMC.