Efecto cardiometabólico de un aceite de oliva virgen enriquecido con componentes bioactivos de la propia aceituna

Abstract

Virgin olive oil (VOO) is a heart-healthy fat for its content of oleic acid and minor compounds: phenols and triterpenic acids. The evidence shows that the intake of VOOs with a high content of polyphenols (150-800 mg/kg of oil) improves plasma inflammatory biomarkers and cholesterol, as well as arterial hypertension (AH) (George et al., 2019). In addition to antihypertensive and antioxidant actions, triterpenic acids regulate several factors related to metabolic syndrome (Sharma et al., 2018). These compounds are present in the by-products of the olive grove, where they can be extracted to enrich the oils and their functional properties. Metabolomics helps to identify the VOO components responsible for the beneficial activity and the molecular mechanisms underlying those effects (Olmo-García and Carrasco-Pancorbo., 2021). The hypothesis of this Doctoral Thesis is based on that the supplementation with VOOs enriched in bioactive compounds can improve cardiovascular health and its associated risk factors The general objective of the Doctoral Thesis is to evaluate the effect of VOOs enriched with bioactive compounds obtained from olives and olive leaves on hypertension and metabolic risk factors associated with cardiovascular risk. Two studies have been proposed: The CARDIOLIVE study has evaluated the effect of 8-weeks oral supplementation with a VOO enriched with olive and olive leaf extracts, with a concentration of 749.9 mg/kg of polyphenols and 292.6 mg/kg of triterpenic acids compared to an oil with a low concentration 17.6 mg/kg in an experimental model of rats with genetic hypertension (SHR). The specific objectives have been the evaluation of the effect of oil enriched in bioactive compounds on: 1) blood pressure, 2) heart morphology, 3) ex-vivo endothelial dysfunction, and 4) oxidation and inflammation plasma biomarkers. In addition, a metabolomic study has been carried out to identify metabolic pathways affected during hypertension and the effects of the VOO. Materials and methods: 10 animals were included per group of rats that took 1 mL/d of the corresponding oil, and 10 control SHR rats and a healthy control group of Wistar Kyoto rats that received 1 mL/d of water. The results of this study show that treatment for 8 weeks with 1 mL/d of a VOO enriched with extracts rich in polyphenols and triterpenes in suspension reduces systolic blood pressure (SBP), cardiac hypertrophy and the secretion of angiotensin II, endothelin -1 and nitrites in hypertensive rats. In addition, improves the functionality of the aortas ex-vivo and the concentrations of plasma oxidation biomarkers and cholesterol. The beneficial effect on some of these biomarkers also occurred after consumption of the control VOO, but was not reflected in a decrease in SBP, which demonstrates an effect of the added bioactive components that are carried in the VOO. The results of the metabolomic analyses has allowed us the annotation of 12 metabolites (6 in urine and 6 in plasma). The urinary metabolomic profile of SHR rats treated with VOO control showed higher amounts of enterolactone and isoflavones compared to SHR and enriched VOO animals. In the plasmatic metabolomic profile, SHR rats treated with enriched VOO showed higher amounts of glycerophospholipids and lysophospholipids. The enrichment analysis identified three metabolic pathways affected in sick untreated SHR rats versus WKY rats, these pathways are: purine metabolic pathway (uric and urate), amino acid metabolic pathway (tyrosine and phenylalanine) and biosynthesis of steroid hormones, which confirms that the rat SHR is suitable for study of the pathophysiology of hypertension. Our data suggest that the intestinal microbiota is determinant for the production of certain metabolites, which play a fundamental role in maintaining cardiovascular function, Therefore, future nutritional intervention studies in animals and humans should be complemented with intestinal microbiota analysis. In the NUTRAOLEUM study, the postprandial effect was evaluated in healthy humans (n=18), of an optimized extra VOO (EVOO) with 490 mg/kg of polyphenols and few triterpenic acids (86 mg/kg); a standard VOO with 124 mg/kg of polyphenols and 86 mg/kg of triterpenic acids; and a functional VOO prepared from the optimized EVOO (487 mg/kg polyphenols) with added olivederived triterpenic acids (388.8 mg/kg). The specific objective has been to evaluate the effect of intake of a dose of 30 mL of the three different oils on the glycemic response, insulin, incretins and gastrointestinal hormones involved in the regulation of appetite and satiety. Different indices of pancreatic functionality (HOMA-β), insulin secretion (INSI), insulin resistance (HOMA-IR), and insulin sensitivity (QUICKI and Matsuda) were calculated. The data show that the intake of olive oil enriched with polyphenols and triterpenic acids improves the functionality of insulin by increasing its secretion (INSI) and peripheral sensitivity (Matsuda) suggesting a synergistic effect between polyphenols and triterpenic acids. Conclusions Our results help to understand the effects of VOO and its minor components on cardiovascular health and associated risk factors. However, more studies are needed to confirm the synergistic effect of polyphenols and triterpenic acids present in VOO and to identify the molecular mechanisms responsible for the beneficial effects on cardiometabolic health and the associated risk factors.