Abstract 9957: Totum-070 Prevents Diet-Induced Hypercholesterolemia in Western Diet Fed Mice

It is well known that hypercholesterolemia is an important modifiable risk factor in the development of cardiovascular disease. Lowering blood cholesterol level reduces the incidence of atherosclerotic disease. TOTUM-070 (T070) is a clinical stage polyphenol-rich active substance composed by the association of 5 plant extracts. We assessed the hypothesis that administration of T070 prevents hypercholesterolemia in western diet fed mice and explored the potential mechanisms involved. C57BL/6 mice were fed either a normal diet (ND) or western diet (WD) for 6 weeks and received either vehicle or T070 (1mg/kg or 3mg/kg) daily by gavage (n=14 mice per group). Supplementation with T070 had no effect on food intake along the study duration. At the end of the study, body weight in WD-fed mice was increased to 28.3 ± 0.8 g compared to the ND group (24.5 ± 0.4 g, p<0.001). Interestingly, a significant (p<0.01) 29% reduction in body weight gain was observed in the T070 3mg/kg group compared to the WD group at the end of the study. Compared to WD group (298 ± 8 mg/dl), total-cholesterol in mice supplemented by T070 was reduced in a dose dependent manner (276 ± 9 mg/dl T070 1mg/kg, (p=0.19) and 265 ± 8 mg/dl T070 3mg/kg, p<0.05). There was no change in triglyceridemia among the groups compared to the ND mice. However, hepatic steatosis induced by the WD was reduced by 73% (p<0.001) in the T070 3mg/kg group. Hepatic and intestinal gene expression were drastically altered by WD feeding compared to ND, while supplementation with T070 tended to restore normal level of expression of many genes implicated in lipid and lipoprotein metabolism. A significant increase in feces production was observed in mice supplemented with T070 3 mg/g compared to the mice fed with WD alone (234 ± 7 mg/day WD+T070 3mg/g vs 207 ± 6 mg/day WD, p<0.01), probably contributing to the beneficial phenotype induced by T070 administration. In conclusion, our results demonstrate the beneficial effect of supplementation with TOTUM-070 to prevent induction of hypercholesterolemia in a nutritional mouse model. This study highlights the interest of using TOTUM-070 for management of mild hypercholesterolemia.