A High Docosahexaenoic Acid Diet Alters the Lung Inflammatory Response to Acute Dust Exposure

Agricultural workers are at risk for the development of acute and chronic lung diseases due to their exposure to organic agricultural dusts. A diet intervention using the omega-3 fatty acid docosahexaenoic acid (DHA) has been shown to be an effective therapeutic approach for alleviating a dust-induced inflammatory response. We thus hypothesized a high-DHA diet would alter the dust-induced inflammatory response through the increased production of specialized pro-resolving mediators (SPMs). Mice were pre-treated with a DHA-rich diet 4 weeks before being intranasally challenged with a single dose of an extract made from dust collected from a concentrated swine feeding operation (HDE). This omega-3-fatty-acid-rich diet led to reduced arachidonic acid levels in the blood, enhanced macrophage recruitment, and increased the production of the DHA-derived SPM Resolvin D1 (RvD1) in the lung following HDE exposure. An assessment of transcript-level changes in the immune response demonstrated significant differences in immune pathway activation and alterations of numerous macrophage-associated genes among HDE-challenged mice fed a high DHA diet. Our data indicate that consuming a DHA-rich diet leads to the enhanced production of SPMs during an acute inflammatory challenge to dust, supporting a role for dietary DHA supplementation as a potential therapeutic strategy for reducing dust-induced lung inflammation

Breast milk DHA levels may increase after informing women: a community-based cohort study from South Dakota USA

Abstract Background Docosahexaenoic acid (DHA), an omega-3 fatty acid found in breast milk, has many health benefits for both mother and baby. A 2007 meta-analysis found U.S. women had breast milk DHA levels (0.20% of total fatty acids) below the worldwide mean (0.32%). In 2008, international dietary recommendations were made for pregnant and lactating women to consume 200\ua0mg of DHA per day. This community-based study aimed to define current milk DHA levels from upper Midwest USA lactating mothers and to determine if providing information about their own level along with dietary recommendations would incite changes to increase breast milk DHA content. Methods New mothers attending lactation classes or using hospital pumping rooms in Sioux Falls, South Dakota, USA participated by providing one drop of breast milk on a card for fatty acid analysis at baseline and 1 month after initial reporting. DHA levels were analyzed by gas chromatography. Mothers received a report of their own breast milk level along with dietary recommendations on DHA intake for lactating women. Median baseline and follow-up DHA levels were determined and differences were compared by Wilcoxon signed-rank test. Results At baseline, breast milk DHA content ( n \u2009=\u200984) was highly variable (range 0.05 to 0.73%) with a median of 0.18% (IQR, 0.13, 0.28; mean\u2009\ub1\u2009SD, 0.22\u2009\ub1\u20090.13%), well below the worldwide average (0.32%). Women who reported taking DHA supplements ( n \u2009=\u200943) had higher levels than those who did not (0.23% vs. 0.15%, P \u2009<\u20090.0001). In a subset of 60 mothers who submitted a second sample, median breast milk DHA content increased from 0.19 to 0.22% ( P \u2009<\u20090.01). Conclusions Findings suggest that providing nursing mothers with their breast milk DHA level and education about DHA intake while breastfeeding motivates change to increase DHA levels

Age Related Bioenergetics Profiles in Isolated Rat Cardiomyocytes Using Extracellular Flux Analyses.

Mitochondrial dysfunction is increasingly recognized and studied as a mediator of heart disease. Extracellular flux analysis (XF) has emerged as a powerful tool to investigate cellular bioenergetics in the context of cardiac health and disease, however its use and interpretation requires improved understanding of the normal metabolic differences in cardiomyocytes (CM) at various stages of maturation. This study standardized XF analyses methods (mitochondrial stress test, glycolytic stress test and palmitate oxidation test) and established age related differences in bioenergetics profiles of healthy CMs at newborn (NB1), weaning (3WK), adult (10WK) and aged (12-18MO) time points. Findings show that immature CMs demonstrate a more robust and sustained glycolytic capacity and a relative inability to oxidize fatty acids when compared to older CMs. The study also highlights the need to recognize the contribution of CO2 from the Krebs cycle as well as lactate from anaerobic glycolysis to the proton production rate before interpreting glycolytic capacity in CMs. Overall, this study demonstrates that caution should be taken to assure that translatable developmental time points are used to investigate mitochondrial dysfunction as a cause of cardiac disease. Specifically, XF analysis of newborn CMs should be reserved to study fetal/neonatal disease and older CMs (≥10 weeks) should be used to investigate adult disease pathogenesis. Knowledge gained will aid in improved investigation of developmentally programmed heart disease and stress the importance of discerning maturational differences in bioenergetics when developing mitochondrial targeted preventative and therapeutic strategies for cardiac disease

Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of Cardiometabolic Genes in Newborn Rats

Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-gestation diabetes, especially in conjunction with a maternal high-fat (HF) diet, impairs cardiac functions in rat-offspring. This study investigated changes in genome-wide histone modifications in newborn hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin-immunoprecipitation-sequencing revealed a differential peak distribution on gene promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR &lt; 0.1). In the HF-diet exposed offspring, 54% of the annotated genes showed the gene-activating mark trimethylated lysine 4. Many of these genes (1) are associated with the “metabolic process” in general and particularly with “positive regulation of cholesterol biosynthesis” (FDR = 0.03); (2) overlap with 455 quantitative trait loci for blood pressure, body weight, serum cholesterol (all, FDR &lt; 0.1); and (3) are linked to cardiac disease susceptibility/progression, based on disease ontology analyses and scientific literature. These results indicate that maternal HF-diet changes the cardiac histone signature in offspring suggesting a fuel-mediated epigenetic reprogramming of cardiac tissue in utero

Strategies to Improve Adolescent Food Security from the Perspectives of Policy Advocates, Parents, and Adolescents

This study explored strategies to improve adolescent food security using semi-structured in-depth interviews with 9 policy advocates, 12 parents and 15 adolescents aged between 17 and 20 years, living in households who were eligible for the Supplemental Nutrition Assistance Program in 2020. This study was part of a larger evaluation of adolescent food insecurity conducted in Baltimore, Maryland, USA during the COVID-19 pandemic. Three key strategies arose during analysis&mdash;improving federal nutrition assistance programs for households, federal nutrition assistance programs for individual adolescents, and leveraging school programs and resources. Respondents described concordant views regarding the role of the Supplemental Nutrition Assistance Program in supporting households but held discordant views about the role of other federal programs, such as the school nutrition programs and Pandemic Electronic Benefit Transfer program. The results of this study provide important insights about policy and programmatic supports that may assist adolescents to acquire food for themselves and their families. Future research should test how federal programs and policies specifically impact food security and nutrition for adolescents

Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes

Offspring born to diabetic or obese mothers have a higher lifetime risk of heart disease. Previously, we found that rat offspring exposed to late-gestational diabetes mellitus (LGDM) and maternal high-fat (HF) diet develop mitochondrial dysfunction, impaired cardiomyocyte bioenergetics, and cardiac dysfunction at birth and again during aging. Here, we compared echocardiography, cardiomyocyte bioenergetics, oxidative damage, and mitochondria-mediated cell death among control, pregestational diabetes mellitus (PGDM)-exposed, HF-diet-exposed, and combination-exposed newborn offspring. We hypothesized that PGDM exposure, similar to LGDM, causes mitochondrial dysfunction to play a central, pathogenic role in neonatal cardiomyopathy. We found that PGDM-exposed offspring, similar to LGDM-exposed offspring, have cardiac dysfunction at birth, but their isolated cardiomyocytes have seemingly less bioenergetics impairment. This finding was due to confounding by impaired viability related to poorer ATP generation, more lipid peroxidation, and faster apoptosis under metabolic stress. To mechanistically isolate and test the role of mitochondria, we transferred mitochondria from normal rat myocardium to control and exposed neonatal rat cardiomyocytes. As expected, transfer provides a respiratory boost to cardiomyocytes from all groups. They also reduce apoptosis in PGDM-exposed males, but not in females. Findings highlight sex-specific differences in mitochondria-mediated mechanisms of developmentally programmed heart disease and underscore potential caveats of therapeutic mitochondrial transfer

Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes

Offspring born to diabetic or obese mothers have a higher lifetime risk of heart disease. Previously, we found that rat offspring exposed to late-gestational diabetes mellitus (LGDM) and maternal high-fat (HF) diet develop mitochondrial dysfunction, impaired cardiomyocyte bioenergetics, and cardiac dysfunction at birth and again during aging. Here, we compared echocardiography, cardiomyocyte bioenergetics, oxidative damage, and mitochondria-mediated cell death among control, pregestational diabetes mellitus (PGDM)-exposed, HF-diet-exposed, and combination-exposed newborn offspring. We hypothesized that PGDM exposure, similar to LGDM, causes mitochondrial dysfunction to play a central, pathogenic role in neonatal cardiomyopathy. We found that PGDM-exposed offspring, similar to LGDM-exposed offspring, have cardiac dysfunction at birth, but their isolated cardiomyocytes have seemingly less bioenergetics impairment. This finding was due to confounding by impaired viability related to poorer ATP generation, more lipid peroxidation, and faster apoptosis under metabolic stress. To mechanistically isolate and test the role of mitochondria, we transferred mitochondria from normal rat myocardium to control and exposed neonatal rat cardiomyocytes. As expected, transfer provides a respiratory boost to cardiomyocytes from all groups. They also reduce apoptosis in PGDM-exposed males, but not in females. Findings highlight sex-specific differences in mitochondria-mediated mechanisms of developmentally programmed heart disease and underscore potential caveats of therapeutic mitochondrial transfer

XF Analyses of Isolated Cardiomyocytes.

<p>Examples of real-time trace oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) during extracellular flux analyses using (A) mitochondrial stress test, (B) glycolytic stress test and (C) palmitate oxidation test. Data points represent mean of three readings taken at each time-point. Drug injections are shown for each test and boxes visually depict computed data.</p

Mitochondrial stress test of cardiomyocytes at various maturational ages.

<p>XF trace (A) and bar graph (B) illustrates OCR changes (from baseline) in NB1, 3WK, 10WK, and 12–18MNTH CMs during mitochondrial stress testing. For group comparisons OCR was normalized to baseline prior to addition of Oligomycin, FCCP and Rotenone/Antimycin A where indicated. Respiratory control ratio (C) and coupling efficiency (D) as calculated from traces are compared between groups. Data are expressed as means ± SEM of 4–7 independent experiments. *p<0.05 by one-way ANOVA and Tukey’s post-test.</p

Glycolysis stress test of cardiomyocytes at various maturational ages.

<p>Extra-cellular acidification rate (ECAR) traces (A) and bar graphs (B) show the glycolytic response of NB1, 3WK, 10WK and 12–18MTH old cardiomyocytes in response to glucose and oligomycin injection where indicated. Data shown are means ± SEM of 3–5 independent experiments. *p<0.05 by one way ANOVA and Tukey’s post-test.</p