Atherosclerotic cardiovascular disease is the leading cause of mortality worldwide, and hypercholesterolemia is a central risk factor for atherosclerosis. This study evaluated the effects of Totum... Show moreAtherosclerotic cardiovascular disease is the leading cause of mortality worldwide, and hypercholesterolemia is a central risk factor for atherosclerosis. This study evaluated the effects of Totum-070, a plant-based polyphenol-rich supplement, in hamsters with high-fat diet (HFD)-induced dyslipidemia. The molecular mechanisms of action were explored using human Caco2 enterocytes. Totum-070 supplementation reduced the total cholesterol (-41%), non-HDL cholesterol (-47%), and triglycerides (-46%) in a dose-dependent manner, compared with HFD. HFD-induced hepatic steatosis was also significantly decreased by Totum-070, an effect associated with the reduction in various lipid and inflammatory gene expression. Upon challenging with olive oil gavage, the post-prandial triglyceride levels were strongly reduced. The sterol excretion in the feces was increased in the HFD-Totum-070 groups compared with the HFD group and associated with reduction of intestinal cholesterol absorption. These effects were confirmed in the Caco2 cells, where incubation with Totum-070 inhibited cholesterol uptake and apolipoprotein B secretion. Furthermore, a microbiota composition analysis revealed a strong effect of Totum-070 on the alpha and beta diversity of bacterial species and a significant decrease in the Firmicutes to Bacteroidetes ratio. Altogether, our findings indicate that Totum-070 lowers hypercholesterolemia by reducing intestinal cholesterol absorption, suggesting that its use as dietary supplement may be explored as a new preventive strategy for cardiovascular diseases. Show less
Fernandez-Castillejo, S.; Pedret, A.; Catalan, U.; Valls, R.M.; Farras, M.; Rubio, L.; ... ; Sola, R. 2021
Scope The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function.Methods and results A randomized, controlled, double-blind, crossover trial... Show moreScope The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function.Methods and results A randomized, controlled, double-blind, crossover trial (33 hypercholesterolaemic subjects) is performed with a control virgin olive oil (VOO), VOO enriched with its own phenolic compounds (FVOO), or VOO enriched with additional phenolic compounds from thyme (FVOOT) for 3 weeks. HDL lipidomic analyses are performed using the Lipidyzer platform. VOO and FVOO intake increase monounsaturated-fatty acids (FAs) and decrease saturated and polyunsaturated FAs in triacylglyceride (TAG) species, among others species. In contrast, FVOOT intake does not induce these FAs changes. The decrease in TAG52:3(FA16:0) after VOO intake and the decrease in TAG52:5(FA18:2) after FVOO intake are inversely associated with changes in HDL resistance to oxidation. After FVOO intake, the decrease in TAG54:6(FA18:2) in HDL is inversely associated with changes in HDL cholesterol efflux capacity.Conclusion VOO and FVOO consumption has an impact on the HDL lipidome, in particular TAG species. Although TAGs are minor components of HDL mass, the observed changes in TAG modulated HDL functionality towards a cardioprotective mode. The assessment of the HDL lipidome is a valuable approach to identify and characterize new biomarkers of HDL function. Show less
