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| Status |
Public on Jun 30, 2023 |
| Title |
Totum-070, a nutritional combination of plant extracts, prevents hypercholesterolemia in high fat diet-fed hamsters by inhibiting intestinal cholesterol absorption |
| Organism |
Mesocricetus auratus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Atherosclerotic cardiovascular disease is the leading cause of mortality worldwide. Hypercholesterolemia is a risk factor of atherosclerosis. This study evaluated the effects of three doses of Totum-070 (3.5%, 4.25% and 5% of diet for 12 weeks; HFD-Totum-070 groups), a plant-based polyphenol-rich supplement, in hamsters with high-fat diet (HFD)-induced dyslipidemia (HFD group). Several functional tests were performed in vivo to characterize the effect of Totum-070 on lipoprotein metabolism. Molecular mechanisms of action were explored using human Caco2 enterocytes. Totum-070 supplementation reduced total cholesterol (-41%), non-HDL cholesterol (-47%) and triglycerides (-46%) in a dose-dependent manner, compared with HFD, without any effects on food intake or body weight. HFD-induced steatosis also was significantly decreased. Gene expression analysis in liver and intestine highlighted Totum-070 effects on metabolic pathways and a strong anti-inflammatory effect. Upon challenge with olive oil gavage, post-prandial lipemia was strongly reduced. Sterol excretion in the feces was increased in the HFD-Totum-070 groups compared with the HFD group. The dual isotope cholesterol absorption test confirmed the reduction of intestinal cholesterol absorption in Totum-070 supplemented hamsters. These effects were confirmed in Caco2 cells where incubation with Totum-070 inhibited cholesterol uptake and apolipoprotein B secretion. Furthermore, metagenomic analysis of gut microbiota revealed a strong effect of Totum-070 on alpha and beta diversity measures. Compared with the HFD group, the Firmicutes to Bacteroidetes ratio was beneficially reduced in the HFD-hamsters supplemented with Totum-070 groups. Altogether, these findings indicate that Totum-070-mediated inhibition of intestinal cholesterol absorption limits the rise in blood cholesterol in high-fat fed hamsters.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for hamster livers from 3 experimental groups: hamsters fed with a Normal Diet (ND), hamsters fed with a High Fat Diet (HFD) and hamsters fed with HFD supplemented with Totum-070 (HFD-T070 5%)
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| Contributor(s) |
Langhi C |
| Citation(s) |
38140315 |
| |
| Submission date |
Mar 15, 2023 |
| Last update date |
Jan 03, 2024 |
| Contact name |
Cédric Langhi |
| E-mail(s) |
cedric.langhi@valbiotis.com
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| Organization name |
Valbiotis
|
| Street address |
20-22 rue Henri et Gilberte Goudier
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| City |
Riom |
| ZIP/Postal code |
63200 |
| Country |
France |
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| Platforms (1) |
| GPL24490 |
Illumina NextSeq 500 (Mesocricetus auratus) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA945002 |
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