MTHFR Polymorphisms and Cardiac Parameters in Patients with Diabetic Retinopathy.

BACKGROUND: Diabetes Mellitus (DM) is directly associated with cardiovascular dysfunctions and microvascular complications, such as diabetic retinopathy (DR). The association between DR and increased risks of developing cardiovascular diseases has been described. The low activity of the Methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the metabolism of homocysteine, can lead to hyperhomocysteinemia that has already been related to cardiac outcomes and resistance to insulin. The A1298C and C677T polymorphisms in the MTHFR can reduce enzyme activity. OBJECTIVE: The study aims to analyze the association between MTHFR genotypes and cardiac parameters in patients with DR. METHODS: DM patients diagnosed with DR (n=65) were categorized and compared according to MTHFR genotypes A1298C (AA and AC+CC groups) and C677T (CC and CT+TT) groups; biochemical, cardiological, anthropometric, genetic, lifestyle and vitamin B9 and B12 consumption variables. Fischer's exact test and Poisson regression were performed to assess the relationship between variables. RESULTS: Comparing echocardiographic and electrocardiogram parameters within genotypic groups, we found a significant association between left atrial dilation and C677T polymorphism. Left atrium diameter was higher in the T allele carriers (CT+TT group), with a prevalence ratio of 0.912. This association was confirmed in the regression model, including confounding variables. The other cardiac structural and functional parameters studied were not significantly associated with the A1298C or C677T genotypes. CONCLUSION: The MTHFR C677T genotype may contribute to atrial remodeling in RD patients. We found an association between the diameter of the left atrium and the T allele of the MTHFR C677T polymorphism in patients with DR.

The effect of resveratrol in cardio-metabolic disorders during pregnancy and offspring outcomes: a review.

Resveratrol supplementation during pregnancy and lactation has been associated with a reduced risk of maternal obesity, gestational diabetes mellitus , and preeclampsia. In addition, emerging evidence has shown that maternal resveratrol supplementation diminishes cardio-metabolic disorders in offspring, highlighting its role in modulating adaptative responses involving phenotypical plasticity. Therefore, it is reasonable to infer that administration of resveratrol during pregnancy and lactation periods could be considered an important nutritional intervention to decrease the risk of maternal and offspring cardio-metabolic disorders. To highlight these new insights, this literature review will summarize the understanding emerging from experimental and clinical studies about resveratrol supplementation and its capacity to prevent or minimize maternal and offspring cardio-metabolic disorders.

Maternal consumption of É·3 attenuates metabolic disruption elicited by saturated fatty acids-enriched diet in offspring rats.

BACKGROUND AND AIMS: High-fat diet (HFD) intake during gestation and lactation has been associated with an increased risk of developing cardiometabolic disorders in adult offspring. We investigated whether metabolic alterations resulting from the maternal consumption of HFD are prevented by the addition of omega-3 (É·3) in the diet. METHODS AND RESULTS: Wistar rat dams were fed a control (C: 19% of lipids and É·6:É·3 = 12), HF (HF: 33% lipids and É·6:É·3 = 21), or HF enriched with É·3 (HFω3: 33% lipids and É·6:É·3 = 9) diet during gestation and lactation, and their offspring food consumption, murinometric measurements, serum levels of metabolic markers, insulin and pyruvate sensitivity tests were evaluated. The maternal HFD increased body weight at birth, dyslipidemia, and elevated fasting glucose levels in the HF group. The enrichment of É·3 in the maternal HFD led to lower birth weight and improved lipid, glycemic, and transaminase biochemical profile of the HFω3 group until the beginning of adulthood. However, at later adulthood of the offspring, there was no improvement in these biochemical parameters. CONCLUSION: Our findings show the maternal consumption of high-fat É·3-rich diet is able to attenuate or prevent metabolic disruption elicited by HFD in offspring until 90 days old, but not in the long term, as observed at 300 days old of the offspring.

PPARα Gene Is Involved in Body Composition Variation in Response to an Aerobic Training Program in Overweight/Obese.

The objective of this study was to investigate the relationship of the polymorphism in Intron 7 G/C (rs 4253778) of the peroxisome proliferator-activated receptor alpha (PPARα) gene with the magnitude of changes in the body composition of an overweight and obese population that underwent an aerobic training program. Fifty-eight previously inactive men and women, body mass index (BMI) 31.5 ± 2.8 kg/m2, 46.5% (n = 27) genotyped as CC genotype and 53.5% (n = 31) as CA+AA, underwent a 12-week aerobic training (walking/running). Aerobic capacity (ergospirometry), body composition (DXA), and nutritional assessment were made before and 48 h after the experimental protocol. Two-way ANOVA, chi-square test, and logistic regression were used (p < 0.05). Twenty-seven volunteers (46.5%) were identified as CC genotype and 31 (53.5%) as CA+AA genotype. Time-group interaction showed that there was no difference in these between two allele groups. However, differences in distribution of respondents or nonresponders according to allele A were identified for fat mass (p ≤ 0.003), percentage fat mass (p ≤ 0.002), the waist (p ≤ 0.009), abdomen (p ≤ 0.000), and hip (p ≤ 0.001), this difference being independent for the fat mass. Meanwhile, sex, age, and nutritional management have also been found to be influential factors. It is concluded that the PPARα gene is involved in varying body composition in response to an aerobic training program.

Coconut Oil Supplementation Does Not Affect Blood Pressure Variability and Oxidative Stress: A Placebo-Controlled Clinical Study in Stage-1 Hypertensive Patients.

Exploring an alternative to improve the clinical management of hypertension, we tested the hypothesis that food supplementation with coconut oil (EVCO), alone or combined with aerobic exercise training, could exert an antihypertensive effect (primary outcome) in patients with stage 1 hypertension. Forty-five hypertensive volunteers of both genders participated in a placebo-controlled clinical trial. The volunteers were submitted to 24-hour ambulatory blood pressure monitoring, analysis of blood pressure variability (BPV), measurement of serum malondialdehyde (MDA) and nutritional assessment. Results indicate that EVCO consumption had no adverse effects. The supplementation did not increase the caloric intake compared with placebo, and the dietary constituents were similar between groups, except for the saturated fats, especially lauric acid. The analysis of blood pressure indicated absence of antihypertensive effect of EVCO alone or combined with physical training. Furthermore, no effects on blood pressure variability and oxidative stress were observed in the supplemented hypertensive patients. Thus, despite the results observed in pre-clinical studies, the current clinical study did not provide evidence to support the use of coconut oil as an adjuvant in the management of hypertension in humans.

Effects of probiotic therapy on cardio-metabolic parameters and autonomic modulation in hypertensive women: a randomized, triple-blind, placebo-controlled trial.

BACKGROUND AND AIMS: We assessed the effects of probiotic therapy for 8 weeks on cardiometabolic variables and autonomic function in women medically diagnosed with arterial hypertension. METHODS AND RESULTS: Forty women with arterial hypertension, 20-50 years, were assigned to two groups in this randomized, triple-blind, placebo-controlled clinical trial. Patients in the probiotic group received a daily sachet containing Lactobacillus para casei LPC-37, Lactobacillus rhamnosus HN001, Lactobacillus acidophilus NCFM, and Bifidobacterium lactis HN019 (109 CFU of each strain) for 8 weeks. Patients in the placebo group received identical sachets with polydextrose (1 g day-1, for 8 weeks). Anthropometric, BP, electrocardiogram, biochemical measurements, fecal microbiota composition, and glucose hydrogen breath test were assessed at baseline and after 8 weeks intervention. Anthropometric variables (weight, BMI, and waist circumference) were similar between the two groups (p > 0.05). Probiotic supplementation significantly reduced fasting glucose (change -10.3 mg dL-1, p < 0.05) and cholesterol levels (change -23.6 mg dL-1, p < 0.05), and increased the HDL-cholesterol (change 6.5 mg dL-1, p < 0.05) compared with the baseline condition. Probiotic supplementation lowered, although without statistical significance, systolic BP by about 5 mmHg and diastolic BP by about 2 mmHg in hypertensive women. Lastly, probiotic administration reduced the low frequency (LF) oscillation and LF/high frequency (HF) ratio (p < 0.05) in the frequency domain of heart rate variability, suggesting an improvement in autonomic modulation. CONCLUSION: Probiotic therapy for 8 weeks reduced fasting glucose levels, and improved the lipid profile and autonomic modulation in hypertensive women.

Oxidative stress does not influence weight loss induced by aerobic training in adults: randomized clinical trials.

BACKGROUND: High levels of oxidative stress promote degradation of the cell membrane impairing cellular function in fat oxidation. However, the influence of oxidative stress on exercise-induced weight-loss has not yet been investigated. Therefore, the aim of this study was to verify the influence of a lipidic peroxidation marker (malondialdehyde, MDA) and antioxidant status (total antioxidant capacity marker, TAC) on the magnitude of weight-loss by aerobic-induced exercise in previously sedentary overweight or obese individuals. METHODS: Seventy-five physically inactive adults were randomized into experimental (N.=58) and control (N.=17) groups, who engaged in a 12-week program of aerobic training walking and/or running (3 to 5 days/week) or stretching (1 day/week), respectively. Body composition (DXA), aerobic capacity (ergospirometric) and blood collections for oxidative stress analysis (MDA and TAC) were determined before and after the experimental protocol. Two-way ANOVA for repeated measures or Friedman's test were used to evaluate differences in time/group interaction. Pearson correlation was used to verify the relationship between the variables of oxidative stress and of body composition. RESULTS: Significant reduction was found in fat body mass of experimental when compared to control group (-1.3±1.9 kg versus -0.3±1.3, P=0.04). Experimental group also altered significantly the total body mass (-1.2±4.7 kg; effect size 0.44), body mass index - BMI (-0.3±1.1 effect size 0.37), fat percentage (1.3±1.6%; effect size 0.50) and lean body mass (0.6±1.5 kg; effect size 0.32).There was increase in MDA of 2.3 µmol/L to 2.7 µmol/L (P=0.00), without changes to TAC (25.6±13.9% to 28.0±10.4%). No correlation was found between these variations in body composition with either the initial values of MDA and TAC or delta variation of these indicators of oxidative stress in response to the training program. CONCLUSIONS: Indicators of oxidative stress (MDA and TAC) does not influence the magnitude of weight-loss induced by aerobic training.

Oral administration of Lactobacillus fermentum post-weaning improves the lipid profile and autonomic dysfunction in rat offspring exposed to maternal dyslipidemia.

BACKGROUND: Maternal dyslipidemia alters the gut microbiota composition and contributes to the development of arterial hypertension (AH) in offspring. Here, we evaluated the effects of a new Lactobacillus fermentum probiotic formulation given post-weaning on cardiometabolic parameters and gut microbiota in male and female rat offspring from dams exposed to maternal dyslipidemia during pregnancy and lactation. METHODS: Wistar rats (n = 14) were fed with a control diet (CTL = 7) or a dyslipidemic diet (DLP = 7) during pregnancy and lactation. After weaning, male and female offspring received a standard diet up to 90 days of life. Rats were allocated into three groups: CTL group + saline solution (n = 14); DLP group + saline solution (n = 14) and DLP group receiving a probiotic cocktail (n = 14). A vehicle or probiotic formulation containing L. fermentum 139, L. fermentum 263 and L. fermentum 296 (ratio 1 : 1 : 1, 1 × 109 CFU mL-1) was administered daily by oral gavage for 8 weeks. RESULTS: The intervention with the probiotic formulation of L. fermentum in male and female offspring reduced total cholesterol (TC) and increased HDL-c, but did not affect the insulin resistance induced by maternal dyslipidemia. Additionally, the male and female rats that received the probiotic formulation of L. fermentum demonstrated improvement in fecal Lactobacillus sp. counts, blood pressure and sympathetic tone, without affecting baroreflex modulation. CONCLUSION: The probiotic formulation containing L. fermentum improved the lipid profile and autonomic dysfunction in male and female offspring exposed to maternal dyslipidemia.

Gut microbiota and probiotic intervention as a promising therapeutic for pregnant women with cardiometabolic disorders: Present and future directions.

Maternal cardiometabolic disorders, such as gestational diabetes mellitus, pre-eclampsia, obesity, and dyslipidemia, are the most common conditions that predispose offspring to risk for future cardiometabolic diseases, needing appropriate therapeutic approach. The implications of microbiota in the pathophysiology of maternal cardiometabolic disorders are progressively emerging and probiotics may be a simple and safe therapeutic strategy for maternal cardiometabolic management. In this review, we argue the importance of cardiometabolic dysfunction during pregnancy and/or lactation on the offspring risk for cardiometabolic disease in later life. In addition, we comprehensively discuss the microbial diversity observed in maternal cardiometabolic disorders and we present the main findings on probiotic intervention as a potential strategy for management of maternal cardiometabolic disorders. Current data reveal that gut microbiota may be transmitted from mother to offspring. Whether targeting microbiota with probiotic intervention during the periconceptional period prevents or delays the onset of cardiometabolic disorders in adult offspring should be tested in future clinical trials.

Decrease of the DNA methylation levels of the ADRB3 gene in leukocytes is related with serum folate in eutrophic adults.

BACKGROUND: DNA methylation has been evidenced as a potential epigenetic mechanism related to various candidate genes to development of obesity. Therefore, the objective of this study was to evaluate the DNA methylation levels of the ADRB3 gene by body mass index (BMI) in a representative adult population, besides characterizing this population as to the lipid profile, oxidative stress and food intake. METHODS: This was a cross-sectional population-based study, involving 262 adults aged 20-59 years, of both genders, representative of the East and West regions of the municipality of João Pessoa, Paraíba state, Brazil, in that were evaluated lifestyle variables and performed nutritional, biochemical evaluation and DNA methylation levels of the ADRB3 gene using high resolution melting method. The relationship between the study variables was performed using analyses of variance and multiple regression models. All results were obtained using the software R, 3.3.2. RESULTS: From the stratification of categories BMI, was observed a difference in the average variables values of age, waist-to-height ratio, waist-to-hip ratio, waist circumference, triglycerides and intake of trans fat, which occurred more frequently between the categories "eutrophic" and "obesity". From the multiple regression analysis in the group of eutrophic adults, it was observed a negative relationship between methylation levels of the ADRB3 gene with serum levels of folic acid. However, no significant relation was observed among lipid profile, oxidative stress and food intake in individuals distributed in the three categories of BMI. CONCLUSIONS: A negative relationship was demonstrated between methylation levels of the ADRB3 gene in eutrophic adults individuals with serum levels of folic acid, as well as with the independent gender of BMI, however, was not observed relation with lipid profile, oxidative stress and variables of food intake. Regarding the absence of relationship with methylation levels of the ADRB3 gene in the categories of overweight, mild and moderate obesity, the answer probably lies in the insufficient amount of body fat to initiate inflammatory processes and oxidative stress with a direct impact on methylation levels, what is differently is found most of the times in exacerbated levels in severe obesity.

Influence of the C677T Polymorphism of the MTHFR Gene on Oxidative Stress in Women With Overweight or Obesity: Response to a Dietary Folate Intervention.

The C677T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR) is related to folate metabolism and can alter the levels of biochemical markers.Objective: Investigate the influence of the MTHFR C677T polymorphism on the effects of a dietary folate intervention on oxidative stress in women with overweight or obesity.Methods: Forty-eight adult women with overweight or obesity were subjected to a 24-hour dietary recall, anthropometric measurements, biochemical analysis, and genotyping of the MTHFR C677T polymorphism. They were allocated by convenience sampling to 2 groups, which received 300 g of folate-rich vegetables containing 191 µg/d (Group 1) (n = 24) or 95 µg/d (Group 2) (n = 24) of folate for 8 weeks.Results: The dietary intervention increased the serum folic acid levels in the 2 analyzed groups. The intervention with 191 µg/d of folate led to relevant results in terms of homocysteine levels (p = 0.0005) and total antioxidant capacity (p = 0.0261); the effect was larger among carriers of the TT genotype.Conclusions: The study demonstrated the beneficial effect of folate intake in terms of a TAC elevation for the CC and TT genotypes of the MTHFR C677T polymorphism, an increase in folic acid levels for all genotypes, and a reduction in the Hcy levels for the TT genotype in response to an intervention consisting of an intake of 191 µg/d of folate supplied by vegetables.

Gut microbiota and probiotics intervention: A potential therapeutic target for management of cardiometabolic disorders and chronic kidney disease?

The gut microbiota plays an important role in host metabolism and its dysregulation have been related to cardiometabolic disorders (CMD), such as type 2 diabetes mellitus (T2D), dyslipidemia and arterial hypertension, as well as to chronic kidney diseases (CKD). The implication of the gut microbiota on systemic disorders has been associated with changes in its composition (dysbiosis) as a result of the oxidative unbalance in the body. This alteration may be the result of the adoption of unhealthy lifestyle behavior, including lack of physical activity and fat- or sugar-rich diets, which are largely associated with increased incidence of CMD and CKD. In last years, a number of clinical trials and experimental studies have demonstrated that probiotics can modulate the host metabolism, resulting in amelioration of systemic disease phenotypes by the improvement of dyslipidemia, glycemic profile and blood pressure or CKD parameters. The beneficial effects of probiotics consumption have been associated with their anti-inflammatory, antioxidant and gut-modulating properties. Despite of some mechanistic evidence, these effects are not totally elucidated. The present review summarizes and clarifies the effects of probiotics administration on CMD and CKD using combined evidence from clinical and experimental studies. Considering that the microbiota dysregulation has been associated with inflammation and oxidative stress and consequently with CMD and CKD, supplementation with probiotics is discussed as a strategy for management of CMD and CKD.