Abstract 9729: Totum-070 Prevents Diet-induced Hyperlipidemia in High Fat High Cholesterol Fed Hamsters

Low-density lipoprotein cholesterol (LDL-Chol) is a well-established modifiable risk factor for cardiovascular disease. TOTUM-070 (T070) is a clinical stage patented blend of biomolecules extracted from 5 plant extracts with high content of polyphenols. We tested the hypothesis that T070 administration prevents hyperlipidemia in Syrian hamsters and explored the potential mechanisms involved. Hamsters were fed either normal diet (ND) or high fat high cholesterol diet (HFHCD) with or without T070 mixed at 3.5%, 4.25% and 5% in the diet for 12 weeks (n=16 per group). During the study duration, no effect of T070 on food intake was observed. At the end of the study, no effect of T070 on the final body weight was noticed when hamsters were supplemented with T070 in comparison to the HFHCD group. HFHCD feeding led to a 5-fold increase in blood total cholesterol compared to ND (1141± 49mg/dl vs 221.4 ± 8.8 mg/dl, respectively, p<0.0001), and a 13-fold increase in non-HDL Chol compared to ND (866 ± 43 mg/dl vs 65 ± 9 mg/dl, respectively, p<0.0001). Compared to the HFHCD group, the 3 groups supplemented with T070 at 3.5%, 4.25% and 5% exhibited a dose-dependent decrease in total-Chol (788 ± 61 mg/dl, n.s; 678 ± 41 mg/dl, p<0.01 and 667 ± 37 mg/dl, p<0.01, respectively) and non-HDL Chol (542 ± 61 mg/dl, p<0.05; 455 ± 37 mg/dl, p<0.01 and 455 ± 33 mg/dl, p<0.01, respectively). Serum triglyceride (TG) levels were increased to 1018 ± 103 mg/dl in HFHCD vs. ND (256 ± 24 mg/dl, p<0.0001). T070 had a dose-dependent effect on serum TG levels reduction (709 ± 91 mg/dl T070 3.5%, p<0.05; 605 ± 56 mg/dl T070 4.25%, p<0.001; and 547 ± 57 mg/dl T070 5%, p<0.001) in comparison to the HFHCD group. Analysis of hepatic lipid content revealed strong lipid accumulation in HFHCD (92-fold increase vs ND), while lipid content decreased by 36%, 52% and 44% in the 3.5, 4.25 and 5% supplemented groups, respectively. Lipid metabolism-related gene expression in liver and intestine was altered upon HFHCD compared to ND but tended to return to normal levels in T070 groups. Collectively, our results highlight the beneficial effect of T070 in the management of moderate cholesterol levels.