Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial.

BACKGROUND: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years. METHODS: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements. FINDINGS: 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group. CONCLUSION: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease. TRIAL REGISTRATION: Clinicaltrials.gov number NCT00924937.

Functional foods and nutraceuticals in the treatment of hypercholesterolemia: Statement of the Spanish Society of Arteriosclerosis 2023. / Alimentos funcionales y nutracéuticos en el tratamiento de la hipercolesterolemia: posicionamiento de la Sociedad Española de Arteriosclerosis 2023.

In the management of hypercholesterolemia, besides advising a healthy, plant-based diet, it may be useful to recommend functional foods or nutraceutical with cholesterol-lowering properties. Given the progressive increase in the number of these products and their rising use by the population, the Spanish Society of Arteriosclerosis (SEA) has considered it appropriate to review the available information, select the results of the scientifically more robust studies and take a position on their usefulness, to recommend to health professionals and the general population their potential utility in terms of efficacy and their possible benefits and limitations. The following clinical scenarios have been identified in which these products could be used and will be analyzed in more detail in this document: (1) Hypolipidemic treatment in subjects with statin intolerance. (2) Hypolipidemic treatment «a la carte¼ in individuals in primary prevention. (3) Long-term cardiovascular prevention in individuals with no indication for lipid-lowering therapy. (4) Patients with optimized lipid-lowering treatment who do not achieve therapeutic objectives.

Nutritional recommendations in the prevention and treatment of atherogenic dyslipidemia. / Recomendaciones nutricionales en la prevención y tratamiento de la dislipemia aterogénica. Grupo de Trabajo Dislipemia Aterogénica, Sociedad Española de Arteriosclerosis.

The incorporation of a healthy diet, regular physical exercise and smoking cessation are the initial measures to reduce cardiovascular risk in patients with atherogenic dyslipidemia. In these patients, the nutritional quality of their diet should be improved, replacing foods with a greater atherogenic effect for others with a healthier effect. There is strong evidence that plant-based dietary patterns, low in saturated fatty acids, cholesterol and sodium, with a high content of fiber, potassium and unsaturated fatty acids, are beneficial and reduce the expression of cardiovascular risk factors. This document focuses on the role of nutrition in the prevention and treatment of atherogenic dyslipidemia, providing current evidence to serve as a tool for health professionals in its clinical management. To facilitate the reading of these recommendations, they are presented in a user-friendly table format, with a hierarchy of different levels of evidence.

MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: From the CORDIOPREV study.

BACKGROUND AND AIM: The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide. One of the first actions to reduce the risk of this disease is to implement healthy dietary models; however, no universal dietary strategies have so far been established. In addition, MicroRNAs (miRNAs) are emerging as new biomarkers to predict disease. We aimed to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease. METHODS: All patients from the CORDIOPREV study without T2DM at baseline according to the American Diabetes Association (ADA) diagnostic criteria (n = 462) were included in the present study. Of them, after a median dietary intervention period of 60 months with two diets (Low fat or Mediterranean diets), 107 developed T2DM and 355 subjects did not develop the disease. The plasma levels of 24 miRNAs were measured at baseline by qRT-PCR. The risk of T2DM was evaluated by Cox regression analysis based on the plasma levels of the miRNAs at baseline and according to the dietary intervention. Finally, pathways analyses were carried out to identify target genes regulated by the miRNAs studied and cellular processes which could be associated with T2DM development. RESULTS: Cox regression analyses showed that patients with low plasma levels of miR-145 at baseline showed a higher risk of developing T2DM after consumption of an LFHCC diet. In addition, patients with low levels of miR-29a, miR-28-3p and miR-126 and high plasma levels of miR-150 at baseline showed a higher risk of developing T2DM after consumption of the Med diet. Finally, pathways analysis showed an interaction of miR-126 and miR-29a in the modulation of FoxO, TNF-α, PI3K-AKT, p53 and mTOR signaling, associated with T2DM development. CONCLUSION: Our results suggest that circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent type 2 diabetes mellitus development in patients with cardiovascular disease. CLINICAL TRIALS NUMBER: NCT00924937.

Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies.

Alpha-lipoic acid (ALA) is a natural short-chain fatty acid that has attracted great attention in recent years as an antioxidant molecule. However, some concerns have been recently raised regarding its safety profile. To address the issue, we aimed to assess ALA safety profile through a systematic review of the literature and a meta-analysis of the available randomized placebo-controlled clinical studies. The literature search included EMBASE, PubMed Medline, SCOPUS, Google Scholar, and ISI Web of Science by Clarivate databases up to 15th August 2020. Data were pooled from 71 clinical studies, comprising 155 treatment arms, which included 4749 subjects with 2558 subjects treated with ALA and 2294 assigned to placebo. A meta-analysis of extracted data suggested that supplementation with ALA was not associated with an increased risk of any treatment-emergent adverse event (all p > 0.05). ALA supplementation was safe, even in subsets of studies categorized according to smoking habit, cardiovascular disease, presence of diabetes, pregnancy status, neurological disorders, rheumatic affections, severe renal impairment, and status of children/adolescents at baseline.

The Role of n-3 Fatty Acids in Cardiovascular Disease: Back to the Future.

Cardiovascular disease (CVD) remains the major cause of death and disability worldwide, and residual risk after implementing all current therapies is still high. In this context, the latest (2016) European Cardiology Society/European Atherosclerosis Society guidelines recommend that triglyceride (TG)-lowering drugs should be used in high-risk patients with TGs levels >2.3 mmol/L (200 mg/dL), after lifestyle measures fail to lower them. After several neutral CVD outcome trials with n-3 fatty acids, the Reduction of Cardiovascular Events with EPA-Intervention Trial met its primary end point, that is, among patients with elevated TGs levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower in those who received 4 g of icosapent ethyl daily. In this review, we comment on the findings of previous and recently published randomized controlled CVD outcome trials assessing n-3 fatty acids supplementation. Both efficacy and safety, as well as future perspectives, are discussed.

Mediterranean Diet Supplemented With Coenzyme Q10 Modulates the Postprandial Metabolism of Advanced Glycation End Products in Elderly Men and Women.

Advanced glycation end products (AGEs) and oxidative stress are elevated with aging and dysmetabolic conditions. Because a Mediterranean (Med) diet reduces oxidative stress, serum AGEs levels, and gene expression related to AGEs metabolism in healthy elderly people, we studied whether supplementation with coenzyme Q10 (CoQ) was of further benefit. Twenty participants aged ≥ 65 (10 men and 10 women) were randomly assigned to each of three isocaloric diets for successive periods of 4 weeks in a crossover design: Med diet, Med + CoQ, and a Western high-saturated-fat diet (SFA diet). After a 12-hour fast, volunteers consumed a breakfast with a fat composition similar to the previous diet period. Analyses included dietary AGEs consumed, serum AGEs and AGE receptor-1 (AGER1), receptor for AGEs (RAGE), glyoxalase I (GloxI), and estrogen receptor α (ERα) mRNA levels. Med diet modulated redox-state parameters, reducing AGEs levels and increasing AGER1 and GloxI mRNA levels compared with the SFA diet. This benefit was accentuated by adding CoQ, in particular, in the postprandial state. Because elevated oxidative stress/inflammation and AGEs are associated with clinical disease in aging, the enhanced protection of a Med diet supplemented with CoQ should be assessed in a larger clinical trial in which clinical conditions in aging are measured.

Homocysteine and Non-Cardiac Vascular Disease.

Elevated homocysteine (Hcy) levels are predictors of cardiovascular disease (CVD). Hyperhomocysteinemia has also been associated with total and CVD mortality. However, whether Hcy is just a marker or plays a causal role in CVD remains to be elucidated. In this narrative review, we discuss the associations between Hcy and non-cardiac vascular diseases, namely stroke, peripheral artery disease (PAD), carotid artery disease, chronic kidney disease (CKD), atherosclerotic renal artery stenosis (ARAS), abdominal aortic aneurysm (AAA) and erectile dysfunction (ED). The effects of several drugs on Hcy levels are also considered. Folic acid, vitamin B6 and B12 supplementation can significantly decrease circulating Hcy concentrations but their effects on CVD risk reduction are conflicting. No current guidelines recommend the routine screening of Hcy levels in patients with non-cardiac vascular diseases. Therefore, further research is needed to elucidate the use of Hcy in the clinical practice.

Frying oils with high natural or added antioxidants content, which protect against postprandial oxidative stress, also protect against DNA oxidation damage.

PURPOSE: Using sunflower oil as frying oil increases postprandial oxidative stress, which is considered the main endogenous source of DNA oxidative damage. We aimed to test whether the protective effect of virgin olive oil and oil models with added antioxidants against postprandial oxidative stress may also protect against DNA oxidative damage. METHODS: Twenty obese people received four breakfasts following a randomized crossover design consisting of different oils [virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)], which were subjected to 20 heating cycles. RESULTS: We observed the postprandial increase in the mRNA levels of p53, OGG1, POLB, and GADD45b after the intake of the breakfast prepared with SFO and SOX, and an increase in the expression of MDM2, APEX1, and XPC after the intake of the breakfast prepared with SFO, whereas no significant changes at the postprandial state were observed after the intake of the other breakfasts (all p values <0.05). We observed lower 8-OHdG postprandial levels after the intake of the breakfast prepared with VOO and SOP than after the intake of the breakfast prepared with SFO and SOX (all p values <0.05). CONCLUSIONS: Our results support the beneficial effect on DNA oxidation damage of virgin olive oil and the oil models with added antioxidants, as compared to the detrimental use of sunflower oil, which induces p53-dependent DNA repair pathway activation.

Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study.

BACKGROUND: Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from metabolic syndrome (MetS) affects this response is not established. OBJECTIVE: Our objective was to determine whether the degree of IR influences the effect of substituting high-saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors. DESIGN: In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined. RESULTS: Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA-IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05). CONCLUSIONS: Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features. This study was registered at clinicaltrials.gov as NCT00429195.

Proteome from patients with metabolic syndrome is regulated by quantity and quality of dietary lipids.

BACKGROUND: Metabolic syndrome is a multi-component disorder associated to a high risk of cardiovascular disease. Its etiology is the result of a complex interaction between genetic and environmental factors, including dietary habits. We aimed to identify the target proteins modulated by the long-term consumption of four diets differing in the quality and quantity of lipids in the whole proteome of peripheral blood mononuclear cells (PBMC). RESULTS: A randomized, controlled trial conducted within the LIPGENE study assigned 24 MetS patients for 12 weeks each to 1 of 4 diets: a) high-saturated fatty acid (HSFA), b) high-monounsaturated fatty acid (HMUFA), c) low-fat, high-complex carbohydrate diets supplemented with placebo (LFHCC) and d) low-fat, high-complex carbohydrate diets supplemented with long chain (LC) n-3 polyunsaturated fatty acids (PUFA) (LFHCC n-3). We analyzed the changes induced in the proteome of both nuclear and cytoplasmic fractions of PBMC using 2-D proteomic analysis. Sixty-seven proteins were differentially expressed after the long-term consumption of the four diets. The HSFA diet induced the expression of proteins responding to oxidative stress, degradation of ubiquitinated proteins and DNA repair. However, HMUFA, LFHCC and LFHCC n-3 diets down-regulated pro-inflammatory and oxidative stress-related proteins and DNA repairing proteins. CONCLUSION: The long-term consumption of HSFA, compared to HMUFA, LFHCC and LFHCC n-3, seems to increase the cardiovascular disease (CVD) risk factors associated with metabolic syndrome, such as inflammation and oxidative stress, and seem lead to DNA damage as a consequence of high oxidative stress.

Impact of the consumption of a rich diet in butter and it replacement for a rich diet in extra virgin olive oil on anthropometric, metabolic and lipid profile in postmenopausal women / Impacto del consumo de una dieta rica en mantequilla y su reemplazo por una dieta rica en aceite de oliva virgen extra sobre el perfil antropométrico, metabólico y lipídico en mujeres postmenopáusicas

Objective: to analyze the impact of the substitution of a rich diet in saturated fats with a rich diet in monounsaturated fats on anthropometric, metabolic and lipid profile in postmenopausal women. Material and methods: a prospective, longitudinal and comparative study where 18 postmenopausal women participated in two periods of dietary intervention of 28 days each one: 1) (SAT diet) consumed butter. Caloric formula (CF) = 15% protein, 38% fat. [20% saturated fat (SFA), 12% monounsaturated fat (MUFA) and 47% carbohydrates and 6% polyunsaturated (PUFA)]. b) Period MONO: with extra virgin olive oil (EVOO). CF = 15% protein, 38% fat (<10% SFA, 22% PUFA and 6% MUFA) and 47% carbohydrates. Size and body composition, glucose, insulin, HOMA, TC, HDL-C, LDL-C, VLDL-C, TG, TC/HDL-C, LDL-C/HDL-C, TG/HDL-C and non-HDL-C/HDL.C were measured; dietary Anamnesis/24 hours, daily food record. ANOVA and Bonferroni statistical analysis (SPSS 20) was applied. Results: the age was 56 ± 5 years, BMI 29.8 ± 3.1 kg/m2 , waist circumference: 93.2 ± 10.1 cm, waist/hip ratio: 0.86 ± 0.14, waist/height: 0.59 ± 0.06 and 38.6 ± 4% body fat (NS). Lipid profile: SAT diet increased TC (p< 0.001), LDL-C (p< 0.002) and non HDL-Cholesterol (p< 0.000), HDL-C increased in MONO diet (p< 0.000). SAT diet: TC/HDL-c ratio, Non col HDL-c/HDL-c, LDL-c/HDL-c (p< 0.000) and TG/HDL-c (p< 0.000). In MONO diet decreased TC/HDL-c (p< 0.015) and TG/HDL-c (p< 0.016). Conclusions: the SAT diet increased cardiovascular risk, while the MONO diet decreased the risk to develop the metabolic syndrome components and choronary heart disease (AU)

Objetivo: analizar el impacto de la sustitución de una dieta rica en grasas saturadas por una dieta rica en grasas monoinsaturadas sobre el perfil antropométrico, metabólico y lipídico en mujeres postmenopáusicas. Material y método: estudio prospectivo, longitudinal y comparativo en el que 18 mujeres postmenopáusicas participaron en dos períodos de intervención dietética de 28 días cada uno: 1) (dieta SAT) consumieron mantequilla. Fórmula calórica (FC) = 15% de proteínas, 38% grasas. [20% grasas saturadas (AGS), 12% grasas monoinsaturadas (AGM) y 47% carbohidratos y 6% poliinsaturadas (AGPI)]. 2) Periodo MONO: con aceite de oliva virgen extra (AOVE). Fórmula calórica = 15% de proteínas, 38% grasas (<10% AGS, 22% AGM y 6% AGPI) y 47% carbohidratos. Se midieron dimensión y composición corporal, glicemia, insulina, HOMA, CT, HDL-C, LDL-C, VLDLC, TG, CT/HDL-C, LDL-C/HDL-C/ TG/ HDL-C y CT no HDL-C/HDLC. Anamnesis dietética/24 horas, registro diario de alimentos. Para el análisis estadístico se aplicó ANOVA y BONFERRONI (SPSS 20). Resultados: la edad fue de 56 ± 5 años, IMC: 29,8 ± 3,1 kg/m2 , circunferencia de cintura (CCi): 93,2 ± 10,1 cm, circunferencia cintura/cadera (IC/C): 0,86 ± 0,14, relación cintura/estatura (ICE): 0,59 ± 0,06 y 38,6 ± 4 % de grasa corporal (%GC) (NS). CCi, Dieta SAT al Inicio: 55,6% = RCV, final = 66,7%, dieta MONO = 55,6%. Perfil lipídico: dieta SAT aumentaron CT (p< 0,001), LDL-C (p< 0,002) y colesterol NO HDL-c (p< 0,000), HDL-C aumentó en dieta MONO (p< 0,000). Dieta SAT: Rel. CT/ HDL-c, Col No HDL-c/HDL-c, LDL-c/HDL-c (p< 0,000) y TG/HDL-c (p< 0,000). En dieta MONO disminuyeron CT/HDL-c (p< 0,015) y TG/HDL-c (p< 0,016). Conclusiones: la dieta SAT aumentó el riesgo cardiovascular, mientras que la dieta MONO disminuyó el riesgo de desarrollar los componentes del síndrome metabólico y enfermedades coronarias (AU)

Effects of the Mediterranean diet supplemented with coenzyme q10 on metabolomic profiles in elderly men and women.

BACKGROUND: Characterization of the variations in the metabolomic profiles of elderly people is a necessary step to understand changes associated with aging. This study assessed whether diets with different fat quality and supplementation with coenzyme Q10 (CoQ) affect the metabolomic profile in urine analyzed by proton nuclear magnetic resonance spectroscopy from elderly people. METHODS: Ten participants received, in a cross-over design, four isocaloric diets for 4-week periods each: Mediterranean diet supplemented with CoQ (Med + CoQ diet); Mediterranean diet; Western diet rich in saturated fat diet; low-fat, high-carbohydrate diet enriched in n-3 polyunsaturated fat. RESULTS: Multivariate analysis showed differences between diets when comparing Med + CoQ diet and saturated fat diet, with greater hippurate urine levels after Med + CoQ diet and higher phenylacetylglycine levels after saturated fat diet in women. Following consumption of Med + CoQ, hippurate excretion was positively correlated with CoQ and ß-carotene plasma levels and inversely related to Nrf2, thioredoxin, superoxide dismutase 1, and gp91(phox) subunit of NADPH oxidase gene expression. After saturated fat diet consumption, phenylacetylglycine excretion was inversely related to CoQ plasma level and positively correlated with isoprostanes urinary level. CONCLUSIONS: The association between hippurate excretion and antioxidant biomarkers along with the relationship between phenylacetylglycine excretion and oxidant biomarkers suggests that the long-term consumption of a Med + CoQ diet could be beneficial for healthy aging and a promising challenge in the prevention of processes related to chronic oxidative stress, such as cardiovascular and neurodegenerative disease.

Effect of frying oils on the postprandial endoplasmic reticulum stress in obese people.

The addition of antioxidants to frying oil reduces postprandial oxidative stress and the inflammatory response. ER stress may trigger both inflammation and oxidative stress processes. We aimed to determine the biological effects of the intake of four models of frying oils on postprandial ER stress in peripheral blood mononuclear cells. Twenty obese people received four breakfasts following a randomized crossover design, consisting of muffins made with different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixture of seed oils (SFO/canola oil) with either dimethylpolysiloxane (SOD) or natural antioxidants from olives (SOP) added), which were previously subjected to 20 heating cycles. ER stress was assessed by measuring the mRNA levels of sXBP1, BiP, CRT, and CNX in peripheral blood mononuclear cells. Our study showed that the intake of the muffins made with SFO induced the postprandial increase of the mRNA levels of the ER stress-sensor sXBP1, and the ER stress related chaperones BiP and CRT (all p-values <0.05). The harmful effects associated with the use of SFO as frying oil, in terms of inflammatory response and postprandial oxidative stress, may be partially mediated by the induction of postprandial ER stress.

Effect of dietary fat modification on subcutaneous white adipose tissue insulin sensitivity in patients with metabolic syndrome.

SCOPE: To determine whether the insulin resistance that exists in metabolic syndrome (MetS) patients is modulated by dietary fat composition. METHODS AND RESULTS: Seventy-five patients were randomly assigned to one of four diets for 12 wk: high-saturated fatty acids (HSFAs), high-MUFA (HMUFA), and two low-fat, high-complex carbohydrate (LFHCC) diets supplemented with long-chain n-3 (LFHCC n-3) PUFA or placebo. At the end of intervention, the LFHCC n-3 diet reduced plasma insulin, homeostasis model assessment of insulin resistance, and nonsterified fatty acid concentration (p < 0.05) as compared to baseline Spanish habitual (BSH) diet. Subcutaneous white adipose tissue (WAT) analysis revealed decreased EH-domain containing-2 mRNA levels and increased cbl-associated protein gene expression with the LFHCC n-3 compared to HSFA and HMUFA diets, respectively (p < 0.05). Moreover, the LFHCC n-3 decreased gene expression of glyceraldehyde-3-phosphate dehydrogenase with respect to HMUFA and BSH diets (p < 0.05). Finally, proteomic characterization of subcutaneous WAT identified three proteins of glucose metabolism downregulated by the LFHCC n-3 diet, including annexin A2. RT-PCR analysis confirmed the decrease of annexin A2 (p = 0.027) after this diet. CONCLUSION: Our data suggest that the LFHCC n-3 diet reduces systemic insulin resistance and improves insulin signaling in subcutaneous WAT of MetS patients compared to HSFA and BSH diets consumption.

Peripheral blood mononuclear cells as in vivo model for dietary intervention induced systemic oxidative stress.

Our aim was to assess the use of peripheral blood mononuclear cells (PBMC) as an in vivo cellular model to evaluate diet-induced changes in the oxidative stress status by analyzing the gene expression pattern of NADPH-oxidase subunits and antioxidant genes. A randomized, controlled trial assigned metabolic syndrome patients to 4 diets for 12 weeks each: (i) high-saturated fatty acid (HSFA), (ii) high-monounsaturated fatty acid, and (iii), (iv) two low-fat, high-complex carbohydrate diets supplemented with n-3 polyunsaturated fatty acids or placebo. A fat challenge reflecting the fatty acid composition as the original diets was conducted post-intervention. The mRNA levels of gp91(phox) (P<0.001), p22(phox) (P=0.005), p47(phox) (P=0.001) and p40(phox) (P<0.001) increased at 2h after the intake of the HSFA meal. The expression of SOD1, SOD2, GSR, GPx1, GPX4, TXN, TXNRD1 and Nrf2 increased after the HSFA meal (p<0.05). In contrast, the expression of these genes remained unaltered in response to the other dietary interventions. Our results suggest that the increased expression of antioxidant genes in PBMC seems to be due to the response to the postprandial oxidative stress generated mainly in adipose tissue after the consumption of an HSFA diet.

Olive oil phenolic compounds decrease the postprandial inflammatory response by reducing postprandial plasma lipopolysaccharide levels.

We investigated the molecular mechanisms by which phenolic compounds (phenols) in virgin olive oil reduce the postprandial inflammatory response with the aim of identifying the transcription factor involved and the downstream effects. Olive oil-based breakfasts prepared with virgin olive oil (VOO) with high (398 ppm), intermediate (149 ppm) and low (70 ppm) phenol content were administered to 49 metabolic syndrome patients following a randomized crossover design. The consumption of a high-phenol VOO-based breakfast limited the increase of lipopolysaccharide plasma levels, TLR4, and SOCS3 proteins (p<0.001, p=0.041 and p=0.008, respectively), the activation of NF-κB (p=0.016) and the IL6 (p=0.007 and p=0.048, low and intermediate oil, respectively), IL1B (p=0.002, intermediate oil), and CXCL1 (p=0.001) postprandial gene expression, in peripheral blood mononuclear cells, as compared with the consumption of a breakfast prepared with the same oil but with low or intermediate phenol content. Virgin olive oil phenolic compounds reduce the postprandial inflammatory response in association with postprandial plasma lipopolysaccharide levels.

Postprandial activation of p53-dependent DNA repair is modified by Mediterranean diet supplemented with coenzyme Q10 in elderly subjects.

BACKGROUND: Alterations in the expression levels of genes and proteins involved in oxidative stress and DNA damage response underlie the phenotypic changes associated with aging. We have investigated whether the quality of dietary fat alters postprandial gene expression and protein levels involved in p53-dependent DNA repair and whether the supplementation with Coenzyme Q10 improves this situation in an elderly population. METHODS: Twenty participants were randomized to receive three isocaloric diets each for 4 weeks: Mediterranean diet supplemented with Coenzyme Q10, Mediterranean diet, saturated fatty acid-rich diet. After a 12-hour fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Gadd45a, Gadd45b, OGG1, APE-1/Ref-1, DNApolß, and XPC gene expression and nuclear Gadd45a, APE-1/Ref-1, and DNApolß protein levels were determined in peripheral blood mononuclear cells. RESULTS: Mediterranean diet and Mediterranean diet supplemented with Coenzyme Q10diets downregulated Gadd45a protein levels compared with the saturated fatty acid-rich diet. Moreover, Mediterranean diet supplemented with Coenzyme Q10diet evoked lower postprandial Gadd45a, Gadd45b, XPC, DNApolß and OGG1 gene expression and lower APE-1/Ref-1 and DNApolß protein levels than the saturated fatty acid-rich diet. CONCLUSIONS: Our results support a beneficial effect of Mediterranean diet and Mediterranean diet supplemented with Coenzyme Q10 on DNA damage as compared to the detrimental action of a saturated fatty acid-rich diet, which triggers the p53-dependent DNA repair machinery.

Dietary fat differentially influences the lipids storage on the adipose tissue in metabolic syndrome patients.

PURPOSE: Adipose tissue is now recognized as a highly active metabolic and endocrine organ. Our aim was to investigate the effect of the dietary fat on the two main adipose tissue functions, endocrine and lipid store, by analyzing the adipose tissue gene expression from metabolic syndrome patients. METHODS: A randomized, controlled trial conducted within the LIPGENE study assigned 39 metabolic syndrome patients to 1 of 4 isoenergetic diets: (1) high-saturated fatty acid (HSFA), (2) high-monounsaturated fatty acid (HMUFA), (3) low-fat, high-complex carbohydrate diet supplemented with long-chain n-3 fatty acids (LFHCC n-3), and (4) low-fat, high-complex carbohydrate diet supplemented with placebo (LFHCC), for 12 weeks each. A fat challenge reflecting the fatty acid composition as the original diets was conducted post-intervention. RESULTS: The long-term consumption of HSFA, LFHCC, and LFHCC n-3 diets, but not HMUFA diet, decreased the perilipin fasting mRNA levels. LFHCC diet consumption increased fasting FABP4 expression, while it was reduced by the consumption of LFHCC n-3 diet. LFHCC meal reduced, while LFHCC n-3 meal intake increased postprandial CAV1 expression. CONCLUSION: The quantity and quality of dietary fat induce differential lipid storage and processing related gene expression, which may interact with the expression of adipokines through common regulatory mechanisms.

An acute intake of a walnut-enriched meal improves postprandial adiponectin response in healthy young adults.

A deficit in adiponectin plays an important causal role in insulin resistance and metabolic syndrome. We hypothesized that as seen during the fasting state, the intake of a walnut-enriched meal increased postprandial adiponectin. Twenty-one healthy white men followed a 4-week baseline diet and then consumed 3 fat-loaded meals that included 1 g fat/kg body weight (65% fat) according to a randomized crossover design: olive oil-enriched meal (22% saturated fatty acids [SFA], 38% monounsaturated fatty acids [MUFA], 4% polyunsaturated fatty acids [PUFA]), butter-enriched meal (35% SFA, 22% MUFA, 4% PUFA), and walnut-enriched meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Leptin, resistin, adiponectin, and free fatty acids were determined at 0, 3, 6, and 8.5 hours after the fat load. After the walnut-enriched meal, plasma adiponectin concentrations were higher at 3 and 6 hours (P = .011, P = .046, respectively) compared with the butter-enriched meal and higher at 6 hours compared with the olive oil-enriched meal (P = .036). Free fatty acid levels decreased from baseline at 3 hours after the walnut-enriched meal (P = .001). No differences were observed between the 3 meals for leptin and resistin responses. Our data confirmed a beneficial profile in the postprandial response to walnuts, source of omega-3 PUFA with an increased postprandial adiponectin and lower postprandial free fatty acid responses. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with omega-3 PUFA dietary fat.