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.

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.

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.

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.

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.

Dietary fat alters the expression of cortistatin and ghrelin systems in the PBMCs of elderly subjects: putative implications in the postprandial inflammatory response.

SCOPE: Dietary fat influences systemic inflammatory status, which determines the progression of age-associated diseases. Since somatostatin (SST), cortistatin (CORT), and ghrelin systems modulate inflammatory response, we aim to comprehensively characterize the presence and regulation of the components of these systems in the peripheral blood mononuclear cells (PMBCs), a subset of white blood cells placed at the crossroad between diet and inflammation, in response to diets with different fat composition, and during the postprandial phase in elderly subjects. METHODS AND RESULTS: The applied nutrigenomic, inflammation-related PBMC-based approach revealed that the majority of components of SST/CORT and ghrelin systems are present in the human PBMCs. Particularly, CORT, SST/CORT receptors (sst2, sst3, sst5, and sst5TMD4), ghrelin, its acylating enzyme (GOAT), In1-ghrelin variant, and GHSR1b were detected in PBMCs. Their expression was altered in the long-term by diet composition, and in the short-term, during the postprandial phase. Of particular relevance is the postprandial elevation of CORT, sst2, and sst5 expression in PBMCs of subjects under n-3 PUFAs-enriched diet. CONCLUSION: Our results suggest a potential relevant role of CORT/ssts and ghrelin systems in regulating PBMCs response to nutrient intake, which could help to explain the positive effects of n-3 PUFAs-enriched diets in reducing the inflammatory response.

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.

Antioxidant system response is modified by dietary fat in adipose tissue of metabolic syndrome patients.

Metabolic syndrome (MetS) is associated with high oxidative stress, which is caused by an increased expression of NADPH-oxidase and a decreased expression of antioxidant enzymes in the adipose tissue. Our aim was to evaluate whether the quality and quantity of dietary fat can modify that process. A randomized, controlled trial conducted within the LIPGENE study assigned MetS patients to one of four diets for 12 wk each: (i) high-saturated fatty acid (HSFA), (ii) high-monounsaturated fatty acid (HMUFA), (iii) and (iv) two low-fat, high-complex carbohydrate diet supplemented with n-3 polyunsaturated fatty acids (LFHCC n3), or placebo (LFHCC). A fat challenge reflecting the same fatty acid composition as the original diets was conducted post-intervention. The intake of an HSFA meal induced a higher postprandial increase in gp91phox and p67phox mRNA levels than after the intake of HMUFA, LFHCC and LFHCC n-3 meals (all p-values<0.05). The postprandial decrease in CAT, GPXs and TXNRD1 mRNA levels after the HSFA meal intake was higher than after the intake of HMUFA, LFHCC and LFHCC n-3 meals (all p-values<0.05). The intake of an HSFA meal induced a higher postprandial increase in KEAP1 mRNA levels than after the consumption of the HMUFA (P=.007) and LFHCC n-3 (P=.001) meals. Our study demonstrated that monounsaturated fat consumption reduces oxidative stress as compared to saturated fat by inducing higher postprandial antioxidant response in adipose tissue, and thus, replacing SFA for MUFA may be an effective dietary strategy to reduce the oxidative stress in MetS patients and its pathophysiological consequences.

Nutraceuticals and coronary heart disease.

PURPOSE OF REVIEW: Although many reviews have focused on diet as a determinant of coronary heart disease (CHD), little is known about the use of specific nutrients or food products. The aim of this review was to examine the role of several functional foods, or nutraceuticals, in the prevention or treatment of CHD. RECENT FINDINGS: CHD continues to be one of the main causes of death in modern societies. Far from diminishing, its prevalence and incidence continue to grow and are probably linked to the increase in metabolic disorders such as obesity, diabetes and metabolic syndrome. Numerous preventive measures and treatments are being considered for these metabolic diseases. In this context, nutraceuticals and functional foods are seen as powerful tools for maintaining health and fighting against cardiometabolic risk factors. For example, the association between saturated fat and the development of CHD has been clearly established. However, the consumption of other sources of fat, such as olive oil enriched in monounsaturated fatty acids, has been associated with beneficial cardiovascular effects. SUMMARY: Nutraceuticals have demonstrated physiological effects that have a positive influence on the development of atherosclerosis and therefore of CHD.

The antioxidants in oils heated at frying temperature, whether natural or added, could protect against postprandial oxidative stress in obese people.

We have investigated the effects of the intake of oils heated at frying temperature in order to find an oil model for deep-frying that prevents postprandial oxidative stress. Twenty obese people received four breakfasts following a randomised 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. The intake of SFO-breakfast reduced plasma GSH levels and the GSH/GSSG ratio, increased protein carbonyl levels, and induced a higher gene expression of the different NADPH-oxidase subunits, Nrf2-Keap1 activation, gene expression of the antioxidant enzymes in peripheral blood mononuclear cells and antioxidant plasma activities than the intake of the breakfasts prepared with VOO, SOP and SOX. Oils with phenolic compounds, whether natural (VOO) or artificially added (SOP), or with artificial antioxidant (SOX), could reduce postprandial oxidative stress compared with sunflower oil.

Postprandial changes in the proteome are modulated by dietary fat in patients with metabolic syndrome.

Metabolic syndrome is a multicomponent disorder whose etiology is the result of a complex interaction between genetic, metabolic and environmental factors including dietary habits. Our aim was to identify proteome-diet interactions during the postprandial state after the acute intake of four meals with different qualities of fat in the proteome of peripheral blood mononuclear cells. A randomized controlled trial conducted within the LIPGENE study assigned 39 metabolic syndrome patients to one of four meals: a high-saturated-fatty-acid (HSFA) meal, a high-monounsaturated-fatty-acid (HMUFA) meal and two high-polyunsaturated-fatty-acid (from walnut) (HPUFA) meals supplemented with n-3 PUFA or placebo. We analyzed the postprandial changes in the whole proteome of both nuclear and cytoplasmic fractions of peripheral blood mononuclear cells by two-dimensional proteomics. Twenty-three proteins were differentially expressed. HSFA intake caused the postprandial increase of proteins responding to oxidative stress (HSPA1A, PDIA3 and PSME1) and DNA damage (SMC6), whereas HMUFA intake led to the up-regulation of HSPA1A and PDIA3. HPUFA meal supplementation with n-3 PUFA produced peroxisomal beta-oxidation inhibition by down-regulation of ECH1, a process related to insulin signaling improvement. In conclusion, HSFA meal intake causes deleterious postprandial changes in the proteome in terms of DNA damage and procoagulant state, which reflect a higher postprandial oxidative stress after HSFA meal intake as compared to intake of HMUFA and HPUFA meals. Moreover, the addition of long-chain n-3 PUFA to an HPUFA meal may improve insulin signaling and exerts an anti-inflammatory effect when compared to an HPUFA meal.

Gene-nutrient interactions on the phosphoenolpyruvate carboxykinase influence insulin sensitivity in metabolic syndrome subjects.

BACKGROUND & AIMS: Genetic background may interact with habitual dietary fat composition, and affect development of the metabolic syndrome (MetS). The phosphoenolpyruvate carboxykinase gene (PCK1) plays a significant role regulating glucose metabolism, and fatty acids are key metabolic regulators, which interact with transcription factors and influence glucose metabolism. We explored genetic variability at the PCK1 gene locus in relation to degree of insulin resistance and plasma fatty acid levels in MetS subjects. Moreover, we analyzed the PCK1 gene expression in the adipose tissue of a subgroup of MetS subjects according to the PCK1 genetic variants. METHODS: Insulin sensitivity, insulin secretion, glucose effectiveness, plasma concentrations of C-peptide, fatty acid composition and three PCK1 tag-single nucleotide polymorphisms (SNPs) were determined in 443 MetS participants in the LIPGENE cohort. RESULTS: The rs2179706 SNP interacted with plasma concentration of n - 3 polyunsaturated fatty acids (n - 3 PUFA), which were significantly associated with plasma concentrations of fasting insulin, peptide C, and HOMA-IR. Among subjects with n - 3 PUFA levels above the population median, carriers of the C/C genotype exhibited lower plasma concentrations of fasting insulin (P = 0.036) and HOMA-IR (P = 0.019) as compared with C/C carriers with n - 3 PUFA below the median. Moreover, homozygous C/C subjects with n - 3 PUFA levels above the median showed lower plasma concentrations of peptide C as compared to individuals with the T-allele (P = 0.006). Subjects carrying the T-allele showed a lower gene PCK1 expression as compared with carriers of the C/C genotype (P = 0.015). CONCLUSIONS: The PCK1 rs2179706 polymorphism interacts with plasma concentration of n - 3 PUFA levels modulating insulin resistance in MetS subjects.