Effects of Dietary Pomegranate Extract and Inulin in Mice Fed an Obesogenic Diet

Abstract

BackgroundIt has been demonstrated in animal studies that both polyphenol rich pomegranate extract (PomX) and the oligosaccharide 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 (10%) alone or in combination on cholesterol and lipid metabolism in mice fed a high fat/high sucrose diet.MethodsMale C57BL/6J 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 (10%) 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. PomX increased gene expression of Cyp7a1 and Cyp7b1, key regulators of bile acid synthesis pathways, and significantly increased total bile acids and neutral sterol fecal elimination. Inulin decreased gene expression of key regulators of cholesterol de novo synthesis Srebf2 and Hmgcr. PomX in combination with inulin reduced liver weight and lipid weight significantly compared to the HF/HS control group. PomX showed a trend to decrease liver triglyceride (TG) level, while inulin or PomX in combination with inulin had no effect on both serum and liver TG levels. In the liver, inulin inhibited expression of genes related to fatty acid synthesis (Fas, Acaca) and to fatty acid β‐oxidation (Cpt1a and Cpt2), while PomX increased expression of genes involved in fatty acid β‐oxidation (Cpt2, Acadl and Acadvl).ConclusionDietary supplementation of the HF/HS diet with PomX and inulin decreased hepatic and serum total cholesterol by different mechanisms leading to a significant enhancement of the cholesterol‐lowering effect.Support or Funding InformationThis project was supported by departmental funds of the Center for Human Nutrition, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles