Mediterranean diet and olive oil, microbiota, and obesity-related cancers. From mechanisms to prevention

Olive oil (OO) is the main source of added fat in the Mediterranean diet (MD). It is a mix of bioactive compounds, including monounsaturated fatty acids, phytosterols, simple phenols, secoiridoids, flavonoids, and terpenoids. There is a growing body of evidence that MD and OO improve obesity-related factors. In addition, obesity has been associated with an increased risk for several cancers: endometrial, oesophageal adenocarcinoma, renal, pancreatic, hepatocellular, gastric cardia, meningioma, multiple myeloma, colorectal, postmenopausal breast, ovarian, gallbladder, and thyroid cancer. However, the epidemiological evidence linking MD and OO with these obesity-related cancers, and their potential mechanisms of action, especially those involving the gut microbiota, are not clearly described or understood. The goals of this review are 1) to update the current epidemiological knowledge on the associations between MD and OO consumption and obesity-related cancers, 2) to identify the gut microbiota mechanisms involved in obesity-related cancers, and 3) to report the effects of MD and OO on these mechanisms

Effects of phenol-enriched olive oils on HDL and endothelial functions in cardiovascular risk individuals

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2017-2018La dislipèmia i la hipertensió són factors clàssics de risc cardiovascular, relacionats amb el desenvolupament de l'arteriosclerosi. Donat a què el colesterol de la lipoproteïna d'alta densitat (HDL) ha estat inversament relacionat a l'aterogènesi, les teràpies han estat focalitzades en incrementar el colesterol HDL. Assaigs clínics que han fet augmentar el colesterol HDL han estat associats a un increment de mortalitat, tot i que en estudis recents aquesta ha estat atribuïda a efectes secundaris de la medicació. A més, últimament s'ha publicat que variants genètiques que predisposen a tenir un colesterol-HDL elevat no estan associades a tenir menys risc de patir un event coronari. Tot això ha fet que la funcionalitat de l'HDL sigui considerada com un aspecte més important que la seva quantitat. Els compostos fenòlics (CF) de l'oli d'oliva (OO) són protectors front malalties coronàries del cor incrementant la concentració de colesterol HDL, disminuïnt in vivo el dany oxidatiu a lípids, activant la funció de l'HDL, i millorant la funció endotelial. En aquest context, l'enriquiment de l'oli d'oliva verge (OOV) amb CF és una estrategia prometadora que permet no incrementar el greix consumit, no obstant aquest enriquiment podria tenir una doble acció perquè un excés d'antioxidants podria també revertir-los a pro-oxidants. Olis d'oliva verge funcionals amb antioxidants complementaris, acord amb la seva relació estructura/activitat, podria ser una opció adequada per obtenir més efectes beneficiosos. L'objectiu d'aquest present treball va ser investigar, en humans amb risc cardiovascular, si: (i) un OO verge enriquit amb els seus compostos fenòlics (OOVF; 961 ppm) modula l'expressió gènica de gens relacionats amb l'eflux de colesterol i la funció endotelial, comparat amb un OO verge (OOV; 289 ppm); i si (ii) OOs verge funcionals, un enriquit amb els seus CFOO (OOFV; 500 ppm) i un altre amb els seus CFOO (250 ppm) més CF de la farigola (250 ppm) (OOFVT; total: 500 ppm), podria millorar propietats relacionades amb la funcionalitat de l'HDL en comparació amb un OO verge control (OOV; 80 ppm). Dos assaigs clínics, creuats, aleatoritzats, doble cecs i controlats han estat realitzats: (i) 13 humans pre-/hipertensos van rebre una dosi única de 30 mL de OOV (289 ppm) i OOFV (961 ppm); i (ii) 33 individus hipercolesterolèmics van ingerir 25 mL/dia durant 3 setmanes de OOV (80 ppm), OOVF (500 ppm), i OOVFT (500 ppm). Els resultats indiquen que una dosi única d'OOVF va incrementar l'expressió gènica de gens relacionats amb l'eflux de colesterol comparat amb el consum de OOV, concretament d'ATP binding cassette transporter-A1, scavenger receptor class B type 1, peroxisome proliferator-activated receptors (PPARBP, PPARα, PPARγ, PPARδ), i CD36. A més, aquest consum va augmentar la hiperèmia isquèmica reactiva comparat amb el d'OOV. En aquest sentit, una disminució de l'inhibidor de l'activador del plasminogen-1 va ser observada després de l'OOVF comparat amb l'OOV. Una intervenció sostinguda d'OOVFT va incrementar el percentatge de la subclasse gran d'HDL en comparació a la d'OOV, i també va augmentar els ratios colesterol esterificat/colesterol lliure i fosfolípids/colesterol lliure en HDL comparat amb les intervencions d'OOV i OOVF. A més a més, el consum d'OOVFT va incrementar la massa de lecitin colesterol acil transferasa comparat amb el d'OOV. En conclusió, un consum postprandial d'OOVF millora la transcriptòmica de l'eflux de colesterol, la funció endotelial, i els marcadors de inflamació. També, els beneficis aconseguits amb el consum sostingut de OOVFT sobre el perfil funcional d'HDL han estat demostrats. Els resultats d'aquests estudis suggereixen que el OOVF i el OOVFT podrien ser eines dietètiques útils en el maneig de pacients amb risc cardiovascularDyslipidemia and hypertension are the classical risk factors of cardiovascular diseases related to atherosclerosis development. Due to the fact that high-density lipoprotein (HDL) cholesterol has been inversely related to atherogenesis, therapies have focused on increasing HDL-cholesterol. Clinical trials which augment HDL have shown an increased mortality risk, however, recent studies have attributed to side effects. Moreover, it has lately been reported that genetic variants predisposing to high HDL-C are not associated with a lower risk of suffering a coronary event. All of the above has led to HDL functionality being considered as a more important aspect than its quantity. Olive oil (OO) phenolic compounds (PC) are protective against risk factors for coronary heart disease by increasing HDL cholesterol concentration, decreasing in vivo lipid oxidative damage, enhancing HDL function, and improving endothelial function. Within this context, the enrichment of virgin olive oil (VOO) with PC is a promising strategy as it does not increase the amount of fat consumed, nevertheless such enrichment might have a dual action because an excess of antioxidants could also revert them to pro-oxidants. Functional virgin OOs with complementary antioxidants, according to their structure/activity relationship, could be a suitable option to obtain greater beneficial effects. The scope of the present work was to investigate, in cardiovascular risk subjects, whether: (i) a functional virgin OO enriched with its own OOPC (FVOO; 961 ppm) modulates the cholesterol efflux-related gene expression and endothelial function, compared to a virgin OO (VOO; 289 ppm); and whether (ii) functional virgin OOs, one enriched with its own OOPC (FVOO; 500 ppm) and another with its own OOPC (250 ppm) plus additional complementary PC from thyme (250 ppm) (FVOOT; total: 500 ppm), could improve HDL functionality-related properties versus a virgin OO control (VOO; 80 ppm). Two cross-over, randomized, double blind, control trial were performed: (i) 13 pre-/hypertensive subjects received a single 30 mL dose of VOO (289 ppm) and FVOO (961 ppm); and (ii) 33 hypercholesterolemic individuals ingested 25 mL/day during 3 weeks of VOO (80 ppm), FVOO (500 ppm), FVOOT (500 ppm). The results indicate that a single dose of FVOO increased cholesterol efflux gene expression compared with VOO consumption, specifically ATP binding cassette transporter-A1, scavenger receptor class B type 1, peroxisome proliferator-activated receptors (PPARBP, PPARα, PPARγ, PPARδ), and CD36. Moreover, this consumption augmented ischemic reactive hyperemia versus the VOO one. In this regard, a decrease of circulating plasminogen activator inhibitor-1 was observed after FVOO compared to VOO. A sustained intervention of FVOOT increased large HDL subclass percentage versus VOO, and also augmented esterified cholesterol/free cholesterol and phospholipids/free cholesterol ratios in HDL compared with the VOO and FVOO interventions. In addition, FVOOT consumption increased lecithin-cholesterol acyltransferase mass compared with VOO one. In conclusion, a postprandial consumption of a FVOO improves cholesterol efflux transcriptomics, endothelial function, and inflammatory biomarkers. Furthermore, the benefits achieved with FVOOT sustained consumption on the HDL functional profile have been demonstrated. Data from our studies suggest that FVOO and FVOOT could be a useful dietary tool in the management of cardiovascular risk patients

Functional signatures in non-small-cell lung cancer: a systematic review and meta-analysis of sex-based differences in transcriptomic studies

While studies have established the existence of differences in the epidemiological and clinical patterns of lung adenocarcinoma between male and female patients, we know relatively little regarding the molecular mechanisms underlying such sex-based differences. In this study, we explore said differences through a meta-analysis of transcriptomic data. We performed a meta-analysis of the functional profiling of nine public datasets that included 1366 samples from Gene Expression Omnibus and The Cancer Genome Atlas databases. Meta-analysis results from data merged, normalized, and corrected for batch effect show an enrichment for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways related to the immune response, nucleic acid metabolism, and purinergic signaling. We discovered the overrepresentation of terms associated with the immune response, particularly with the acute inflammatory response, and purinergic signaling in female lung adenocarcinoma patients, which could influence reported clinical differences. Further evaluations of the identified differential biological processes and pathways could lead to the discovery of new biomarkers and therapeutic targets. Our findings also emphasize the relevance of sex-specific analyses in biomedicine, which represents a crucial aspect influencing biological variability in diseaseThis work was supported by Fondo de Investigación Sanitaria (ISCIII PI15-00209), GV/2020/ 186, and ISCIII PT17/0009/0015 FEDE

An Escape-Room about Krebs cycle prepared for Chemical Students

Games are excellent teaching tools for self-learning. Students playing a game enjoy themselves and at the same time learn basic and important concepts. Different games including crossword puzzles, word search puzzles, knight's tour games, connecting dots, mazes, matching two sets, amidakuji, and logic games were used for continuous assessment during the confinement due to pandemic. These games were developed as part of the GINDO-UB180 teaching innovation group activities. Since these games were very successful, we decided to combine all of them and construct a new teaching activity, that would help our students to study one essential metabolic pathway: The Krebs cycle. This activity (https://forms.gle/BPvpnLQRNYNPxcLQ7) is an Escape-room, and it was recently tested by our students in a General Biochemistry course. The code of the Escape room after the game is a word: either the longest in the letter soup, an anagram from several boxes from the crossword puzzles, the sentence from the knight's tour game, or a word obtained following a maze. The results obtained after carrying out the Escape room will be compared with those obtained using previous tasks in terms of assessment and acceptance by the students in order to be included in the future as self-evaluation activities

Characteristics of atheromatosis in the prediabetes stage : A cross-sectional investigation of the ILERVAS project

Background: Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage. Methods: Atheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines. Results: Prediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c < 5.7% (70.4 vs. 67.5%, p = 0.017). In the population with prediabetes this was observed at the level of the carotid territory (p < 0.001), but not in the femoral arteries. Participants in the prediabetes stage also presented a significantly higher number of affected territories (2 [1;3] vs. 1 [0;3], p = 0.002), with a positive correlation between HbA1c levels and the number of affected territories (r = 0.068, p < 0.001). However, atheromatosis was only significantly (p = 0.016) magnified by prediabetes in those subjects with 3 or more cardiovascular risk factors. The multivariable logistic regression model showed that the well-established cardiovascular risk factors together with HbA1c were independently associated with the presence of atheromatous disease in participants with prediabetes. When males and females were analyzed separately, we found that only men with prediabetes presented both carotid and femoral atherosclerosis, as well as an increase of total plaque area in comparison with non-prediabetic subjects. Conclusions: The prediabetes stage is accompanied by an increased subclinical atheromatous disease only in the presence of other cardiovascular risk factors. Prediabetes modulates the atherogenic effect of cardiovascular risk factors in terms of distribution and total plaque area in a sex-dependent manner

Clinical Usefulness of Anthropometric Indices to Predict the Presence of Prediabetes. Data from the ILERVAS Cohort

Prediabetes is closely related to excess body weight and adipose distribution. For this reason, we aimed to assess and compare the diagnostic usefulness of ten anthropometric adiposity indices to predict prediabetes. Cross-sectional study with 8188 overweight subjects free of type 2 diabetes from the ILERVAS project (NCT03228459). Prediabetes was diagnosed by levels of glycated hemoglobin (HbA1c). Total body adiposity indices [BMI, Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) and Deurenberg's formula] and abdominal adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora's equation, A body shape index, and body roundness index) were calculated. The area under the receiver-operating characteristic (ROC) curve, the best cutoff and the prevalence of prediabetes around this value were calculated for every anthropometric index. All anthropometric indices other than the A body adiposity were higher in men and women with prediabetes compared with controls (p < 0.001 for all). In addition, a slightly positive correlation was found between indices and HbA1c in both sexes (r ≤ 0.182 and p ≤ 0.026 for all). None of the measures achieved acceptable levels of discrimination in ROC analysis (area under the ROC ≤ 0.63 for all). Assessing BMI, the prevalence of prediabetes among men increased from 20.4% to 36.2% around the cutoff of 28.2 kg/m2, with similar data among women (from 29.3 to 44.8% with a cutoff of 28.6 kg/m2). No lonely obesity index appears to be the perfect biomarker to use in clinical practice to detect individuals with prediabetes.This work was supported by grants from the Diputació de Lleida and Generalitat de Catalunya (2017SGR696 and SLT0021600250). CIBER de Diabetes y Enfermedades Metabólicas Asociadas and CIBER de Enfermedades Respiratorias are initiatives of the Instituto de Salud Carlos III

Virgin olive oil phenolic compounds modulate the HDL lipidome in hypercholesterolaemic subjects: a lipidomic analysis of the VOHF study

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.The VOHF project (AGL2009-13517-457 C03-01) and the AppleCOR Project (AGL2016-76943-C2) were made possible with the support of the Ministerio de Economía, Indústria y Competitividad, the Agencia Estatal de Investigación, and the European Regional Development Fund. U.C. has a Pla Estratègic de Recerca i Innovació en Salut (PERIS) postdoctoral grant (no. SLT002/16/00239; Catalunya, Spain) from the Generalitat de Catalunya. A.P. has a Torres Quevedo postdoctoral grant with the Subprograma Estatal de Incorporación, Plan Estatal de Investigación Científica Técnica y de Innovación. M.F. has a Sara Borrell postdoctoral contract (CD17/00233 to M.F.-St.Pau). O.C. has a JR17/00022 contract from Instituto de Salud Carlos III. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) is a project of Instituto de Salud Carlos III (Madrid, Spain). The NFOC-Salut group is a consolidated research group of the Generalitat de Catalunya, Spain (reference no. 2017 SGR 522)

Dissimilar Impact of a Mediterranean Diet and Physical Activity on Anthropometric Indices: A Cross-Sectional Study from the ILERVAS Project

There is a close relationship between lifestyle behaviors and excess adiposity. Although body mass index (BMI) is the most used approach to estimate excess weight, other anthropometric indices have been developed to measure total body and abdominal adiposity. However, little is known about the impact of physical activity and adherence to a Mediterranean diet on these indices. Here we report the results of a cross-sectional study with 6672 middle-aged subjects with low to moderate cardiovascular risk from the Ilerda Vascular (ILERVAS) project. The participants' adherence to physical activity (International Physical Activity Questionnaire short form) and MedDiet (Mediterranean Diet Adherence Screener) was evaluated. Measures of total adiposity (BMI, Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE), and Deurenberg's formula), central adiposity (waist and neck circumferences, conicity index, waist to height ratio, Bonora's equation, A body adiposity index, and body roundness index), and lean body mass (Hume formula) were assessed. Irrespective of sex, lower indices of physical activity were associated with higher values of total body fat and central adiposity. This result was constant regardless of the indices used to estimate adiposity. However, the association between MedDiet and obesity indices was much less marked and more dependent on sex than that observed for physical activity. Lean body mass was influenced by neither physical activity nor MedDiet adherence. No joint effect between physical activity and MedDiet to lower estimated total or central adiposity indices was shown. In conclusion, physical activity is related to lower obesity indices in a large cohort of middle-aged subjects. MedDiet showed a slight impact on estimated anthropometric indices, with no joint effect when considering both lifestyle variables

Effects of Mediterranean Diet and Physical Activity on Pulmonary Function: A Cross-Sectional Analysis in the ILERVAS Project

A few studies showed that both adherence to Mediterranean diet (MedDiet) and physical activity practice have a positive impact on pulmonary function in subjects with lung disease. These associations are not well studied in subjects free from lung disease. In a cross-sectional study conducted in 3020 middle-aged subjects free of lung disease, adherence to the MedDiet using the Mediterranean Diet Adherence Screener, and physical activity practice using the International Physical Activity Questionnaire short form were recorded. Respiratory function was assessed using forced spirometry and the results were evaluated according to the Global initiative for Chronic Obstructive Lung Disease. Logistic regression models were used to analyze the associations between adherence to the MedDiet and physical activity practice with the presence of ventilatory defects. Participants with a high adherence to MedDiet, in comparison to those with low adherence, had both higher forced vital capacity (FVC; 100 (87–109) vs. 94 (82–105) % of predicted, p = 0.003) and forced expired volume in the first second (FEV1; 100 (89–112) vs. 93 (80–107) % of predicted, p < 0.001). According to their degree of physical activity, those subjects with a high adherence also had both higher FVC (100 (88–107) vs. 94 (83–105) % of predicted, p = 0.027) and FEV1 (100 (89–110) vs. 95 (84–108) % of predicted, p = 0.047) in comparison with those with low adherence. The multivariable logistic regression models showed a significant and independent association between both low adherence to MedDiet and low physical activity practice, and the presence of altered pulmonary patterns, with differences between men and women. However, no joint effect between adherence to MedDiet and physical activity practice on respiratory function values was observed. Low adherence to MedDiet and low physical activity practice were independently associated with pulmonary impairment. Therefore, the lung mechanics seem to benefit from heart-healthy lifestyle behaviors.This study was supported by grants from the Diputació de Lleida, Generalitat de Catalunya (2017SGR696 and SLT0021600250), Instituto de Salud Carlos III (Fondo de Investigación Sanitaria PI12/00803 and PI15/00260), and European Union (European Regional Development Fund, Fondo Europeo de Desarrollo Regional, “Una manera de hacer Europa”). CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBER de Nutrición y Obesidad, and CIBER de Enfermedades Respiratorias are initiatives of the Instituto de Salud Carlos III