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Cholesterol-lowering effects of dietary pomegranate extract and inulin in mice fed an obesogenic diet
Institution:1. State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang 310021, P. R. China;2. Shaanxi Engineering Laboratory for Food Green Processing and Safety Control, College of Food Engineering and Nutritional Science, Normal University, Xi''an 710062, P. R. China;1. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China;2. School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China;3. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China;4. Department of Endocrinology and Metabolism and Institute of Endocrinology, the First Hospital of China Medical University, Shenyang, Liaoning, China;1. Top Institute Food and Nutrition, Wageningen, the Netherlands;2. Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands;3. Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Universiteitssingel 50, 6229 ER Maastricht, the Netherlands;4. Department of HPB Surgery and Liver Transplantation, Institute of Liver and Digestive Health, University College London, Rowland Hill Street, London NW3 2PF, United Kingdom;5. NNF Center for Basic Metabolic Research, Copenhagen, Blegdamsvej 3A, Copenhagen 2200, Denmark;6. Department of Surgery, Universitätsklinikum Aachen, Pauwelsstraße 30, 52074 Aachen, Germany;7. Department of Biomedical Sciences, University of Copenhagen, Nørregade 10, 1165 Copenhagen, Denmark
Abstract:BackgroundIt has been demonstrated in animal studies that both polyphenol-rich pomegranate extract (PomX) and the polysaccharide inulin, ameliorate metabolic changes induced by a high-fat diet, but little is known about the specific mechanisms.ObjectiveThis study evaluated the effect of PomX (0.25%) and inulin (9%) alone or in combination on cholesterol and lipid metabolism in mice.MethodsMale C57BL/6 J mice were fed high-fat/high-sucrose HF/HS (32% energy from fat, 25% energy from sucrose)] diets supplemented with PomX (0.25%) and inulin (9%) alone or in combination for 4 weeks. At the end of intervention, serum and hepatic cholesterol, triglyceride levels, hepatic gene expression of key regulators of cholesterol and lipid metabolism as well as fecal cholesterol and bile acid excretion were determined.ResultsDietary supplementation of the HF/HS diet with PomX and inulin decreased hepatic and serum total cholesterol. Supplementation with PomX and inulin together resulted in lower hepatic and serum total cholesterol compared to individual treatments. Compared to HF/HS control, PomX increased gene expression of Cyp7a1 and Cyp7b1, key regulators of bile acid synthesis pathways. Inulin decreased gene expression of key regulators of cholesterol de novo synthesis Srebf2 and Hmgcr and significantly increased fecal elimination of total bile acids and neutral sterols. Only PomX in combination with inulin reduced liver and lipid weight significantly compared to the HF/HS control group. PomX showed a trend to decrease liver triglyceride (TG) levels, while inulin or PomX-inulin combination had no effect on either serum or liver TG levels.ConclusionDietary PomX and inulin supplementation decreased hepatic and serum total cholesterol by different mechanisms and the combination leading to a significant enhancement of the cholesterol-lowering effect.
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