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.

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.

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.