Prenatal Omega-6:Omega-3 Ratio and Attention Deficit and Hyperactivity Disorder Symptoms

Objective: To evaluate whether higher omega-6:omega-3 (n-6:n-3) long-chain polyunsaturated fatty acid ratio in cord plasma is associated with more symptoms of attention deficit and hyperactivity disorder (ADHD) at 4 and 7 years of age. Study design: This study was based on a population-based birth cohort in Spain. N-6 arachidonic acid and n-3 eicosapentaenoic and docosahexaenoic acid concentrations were measured in cord plasma. At 4 years old, ADHD symptoms were reported by teachers through the ADHD Diagnostic and Statistical Manual of Mental Disorders, 4th ed checklist (n = 580). At 7 years old, ADHD symptoms were reported by parents through the Conners' Rating Scale-Revised (short form; n = 642). The ADHD variable was treated as continuous (score) and as dichotomous (symptom diagnostic criteria). Child and family general characteristics were prospectively collected through questionnaires. We applied pooled zero-inflated negative binomial and logistic regressions adjusted for covariates. Results: A higher omega-6:omega-3 long-chain polyunsaturated fatty acid ratio in cord plasma was associated with a higher ADHD index (incidence rate ratio, 1.13; 95% CI, 1.03, 1.23) at 7 years old. The association was not observed at 4 years old (incidence rate ratio, 1.04; 95% CI, 0.92-1.18). No associations were found using ADHD symptom diagnostic criteria. Conclusions: High prenatal omega-6:omega-3 long-chain polyunsaturated fatty acid ratio preceded the appearance of subclinical ADHD symptoms during mid-childhood. Our findings suggest that maternal diet during pregnancy may modulate the risk to develop long-term ADHD symptoms in the offspring

Neuregulin 4 Is a Novel Marker of Beige Adipocyte Precursor Cells in Human Adipose Tissue

Background: Nrg4 expression has been linked to brown adipose tissue activity and browning of white adipocytes in mice. Here, we aimed to investigate whether these observations could be translated to humans by investigating NRG4 mRNA and markers of brown/beige adipocytes in human visceral (VAT) and subcutaneous adipose tissue (SAT). We also studied the possible association of NRG4 with insulin action.Methods: SAT and VAT NRG4 and markers of brown/beige (UCP1, UCP3, and TMEM26)-related gene expression were analyzed in two independent cohorts (n = 331 and n = 59). Insulin resistance/sensitivity was measured using HOMAIR and glucose infusion rate during euglycemic hyperinsulinemic clamp.Results: In both cohort 1 and cohort 2, NRG4 and thermogenic/beige-related gene expression were significantly increased in VAT compared to SAT. Adipogenic-related genes followed an opposite pattern. In cohort 1, VAT NRG4 gene expression was positively correlated with BMI and expression of UCP1, UCP3, TMEM26, and negatively with adipogenic (FASN, PPARG, and SLC2A4)- and inflammatory (IL6 and IL8)-related genes. In SAT, NRG4 gene expression was negatively correlated with HOMAIR and positively with UCP1 and TMEM26 gene expression. Multiple linear regression analysis revealed that expression of TMEM26 gene was the best predictor of NRG4 gene expression in both VAT and SAT. Specifically, NRG4 and TMEM26 gene expression was significantly increased in VAT, but not in SAT stromal vascular fraction cells (p < 0.001). In cohort 2, the significant association between NRG4 and TMEM26 gene expression in both VAT and SAT was confirmed, and SAT NRG4 gene expression also was positively correlated with insulin action and the expression of UCP1.Conclusion: Current findings suggest NRG4 gene expression as a novel marker of beige adipocytes in human adipose tissue

Molecular phenomics of a high-calorie diet-induced porcine model of prepubertal obesity

As obesity incidence is alarmingly rising among young individuals, we aimed to characterize an experimental model of this situation, considering the similarity between human and porcine physiology. For this reason, we fed prepubertal (63 days-old) Duroc breed females (n=20) either with a standard growth diet (3800 KCal/day) or one with a high-calorie content (5200 KCal/day) during 70 days. Computerized tomography, mass-spectrometry based metabolomics, and lipidomics, as well as peripheral blood mononuclear cell transcriptomics, were applied to define traits linked to high-calorie intake. Samples from a human cohort confirmed potential lipidomic markers. Compared to those fed a standard growth diet, pigs fed a high-calorie diet showed an increased weight gain (13%), much higher adiposity (53%), hypertriacylglyceridemia and hypercholesterolemia, in parallel to insulin resistance. This diet induced marked changes in the circulating lipidome, particularly in phosphatidylethanolamine-type molecules. Also, circulating specific diacylglycerol and monoacylglycerol contents correlated with visceral fat and intrahepatic triacylglycerol concentrations. Specific lipids associated with obesity in swine (mainly belonging to glycerophospholipid, triacylglyceride, and sterol classes) were also linked with obesity-traits in the human cohort, reinforcing the usefulness of the chosen approach. Interestingly, no overt inflammation in plasma or adipose tissue was evident in this model. The presented model is useful as a preclinical surrogate of prepubertal obesity in order to ascertain the pathophysiology interactions between energy intake and obesity development.info:eu-repo/semantics/acceptedVersio

Circulating Zonulin, a Marker of Intestinal Permeability, Is Increased in Association with Obesity-Associated Insulin Resistance

Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity). Circulating zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002) contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01) contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase

Dietary α-Linolenic Acid, Marine ω-3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56-0.92) for all‐cause mortality and 0.95 (95% CI 0.58-1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67-1.05) for all‐cause mortality, 0.61 (95% CI 0.39-0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29-0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22-1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45-0.87]). Conclusions In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Pearson’s correlation among circulating zonulin and metabolic parameter.

<p>NGT, participants with normal glucose tolerance; GI, participants with glucose intolerance; WHR, waist to hip ratio; HbA1c, Glycosylated haemoglobin; IS, insulin sensitivity.</p

Anthropometrical and biochemical parameters from the participants of the study.

<p>NGT, participants with normal glucose tolerance; GI, participants with glucose intolerance; WHR, waist to hip ratio; HbA1c, Glycosylated haemoglobin; IS, insulin sensitivity.</p

Multiple linear regression analysis with circulating zonulin as dependent variable.

<p>Multiple linear regression analysis with circulating zonulin as dependent variable.</p