bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folic acid content of diets during pregnancy imprint early post‐partum hepatic methyl‐metabolism and insulin resistance in Wistar rat dams
Authors: Pannia Emanuela , Ho Mandy , Yang Neil , Chatterjee Diptendu , Hammoud Rola , Kubant Ruslan , Anderson G. Harvey 
Published: November 2023

Intake recommendations for folic acid (FA, synthetic form of folate) are often exceeded by 2.5–7‐fold in North America, raising concern for its potential adverse effects on maternal and child health. In Wistar rats, high (10×) but non‐toxic FA intakes during pregnancy lead to obesity, insulin resistance and dysregulation of central and peripheral energy metabolism‐related genes in both offspring and dams later‐in‐life. Moreover, high FA fed to rat offspring post‐weaning was reported to induce inhibitory effects on hepatic methyl‐metabolism, limiting the conversion of FA to its biologically active form methyltetrahydrofolate (MTHF). This study examined the effects of dose of FA in maternal diets on early post‐partum phenotype (body weight and food intake), folate status, methyl metabolism in liver, and insulin resistance in the dams.During pregnancy, Wistar rats (n=12/group) were fed an AIN‐93G diet containing five levels of FA: 0× (deficient), 1× (recommended, 2mg FA/kg), 2.5× (moderate), 5× (high) and 10× (very high). Dams were fed the recommended diet during lactation and their first week post‐weaning and then terminated. At 1‐week post‐weaning, mRNA expression of methyl metabolism‐related genes in liver, including folate receptor (FolR), Mthf reductase (Mthfr), betaine‐homocysteine S‐methyltransferase (Bhmt) and methionine synthase (Mtr) were assessed by real‐time qPCR. Unmetabolized FA and folate metabolites were analyzed in blood and liver by high performance liquid chromatography (HPLC). Fasting plasma glucose and insulin levels were measured, and insulin resistance was evaluated via surrogate index: the homeostatic model assessment insulin resistance (HOMA‐IR).The results show a lasting effect of the diets consumed during pregnancy on the dams four weeks after giving birth. Dams fed 0X, 5× and 10X‐FA during pregnancy had lower hepatic mRNA expression of Mthfr (2.2‐fold, p<0.0001) and Mtr (3.5‐fold, p<0.001) compared to control and showed no change in folate status in liver. However, deficient and very high FA maternal diets led to higher MTHF in blood compared to control suggestive of dysregulation of one‐carbon pathways. Dams fed 5X‐FA also showed higher plasma insulin (p<0.01) and HOMA‐IR (p<0.05) then dams fed the control diet, indicative of the development of insulin resistance. Body weight, food intake and unmetabolized FA levels were not affected by maternal diets at 1‐week post‐weaning.In conclusion, deficient or excess FA in diets consumed during pregnancy imprinted methyl‐metabolism and insulin regulation in the dam to 1‐week post‐weaning, which may contribute to their long‐term adverse effects as previously found in the dams.Support or Funding InformationCanadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR‐INMD), Reference MOP‐130286
School nutrition programs and policies, dietary intake, and obesity: The Healthy Communities Study
Authors: Au Lauren E , Woodward‐Lopez Gail , Gurzo Klara , Kao Janice , Crawford Patricia , Ritchie Lorrene D 
Published: November 2023

The study objective was to examine the association between the school nutrition environment and children's dietary intake and weight status in an observational sample of 5,138 U.S. children ages 4–15 years recruited from 130 communities in the Healthy Communities Study. The study includes information obtained on school characteristics (school participation in state and federal nutrition programs, school wellness committee and coordinator, and district food‐related school wellness policies), measurements of children's dietary practices (dietary screener and dietary behaviors related to child obesity), and measured child height and weight to calculate BMI z‐score. Hierarchical statistical models were generated to relate school nutrition policies and programs to dietary outcomes and BMI z‐score, adjusted for individual‐level covariates (e.g., child race/ethnicity, household income, maximum parent education, maximum parent employment), community covariates (e.g., region, minority status, urbanicity), and school and community level clustering. Children in schools where wellness committees were more active, i.e. met at least once in the past year, compared to children in schools where wellness committees were less active, i.e. met less than once per year, children had 0.10 lower BMI z‐scores (95% CI: −0.17, −0.02; P=0.02) and consumed breakfast on 0.14 more days/week (95% CI: 0.02, 0.25; P=0.02). Schools with farm to school programs compared to schools without such programs had children with a lower frequency of intake of energy dense foods by −0.19 times/day (95% CI: −0.33, −0.05; P=0.01). The presence of the USDA's Team Nutrition Initiative also was associated with an increase in children's intake of 0.14 servings/day of fruits and vegetables (95% CI: 0.00002, 0.14; P=0.05) compared to schools that did not have the program. In pair‐wise comparisons (at a 5% procedure‐wise error rate), schools with wellness committees that met more than once in the past year compared to schools with wellness committees that did not meet, children had significantly lower added sugar intake (−0.78 tsp/day) and significantly lower sugar intake from sugar‐sweetened beverages (−0.43 tsp/day). Overall, improved child diet and weight outcomes were found when schools had an active wellness committee, involvement in a farm to school program, and/or participated in the USDA's Team Nutrition Initiative.Support or Funding InformationSupported by: NHLBI #1K01HL131630 and RWJF HER #73272.
Serum Alkylresorcinols as Biomarkers of Dietary Gluten Exposure in Celiac disease
Authors: Ross Alastair , Choung Rok Seon , Marietta Eric V , Van Dyke Carol T , Murray Joseph A 
Published: November 2023

BackgroundTherapy for celiac disease (CD) mainly relies on following a gluten‐free diet (GFD); however, a serum marker for gluten intake has yet to be established.AimsTo evaluate the utility of alkylresorcinol concentrations for detecting gluten intake in studies of human and mouse.MethodsAlkylresorcinol concentrations were compared among treated CD patients (n=34), untreated CD patients (n=36), and controls (n=33). Furthermore, 7 additional CD patients whose serum samples were available at diagnosis and after GFD were evaluated. In mice studies, alkylresorcinol concentrations were compared in the serum of 5 mice fed a regular chow and 10 mice fed lifelong with a gluten‐free chow. In addition, the effect of adding gluten on changes of alkylresorcinol concentrations was also evaluated.ResultsTotal alkylresorcinol concentrations were significantly lower in treated CD patients (median [IQR], 3 (2–8) nmol/L), compared to untreated CD patients (median [IQR], 32 [11–74] nmol/L; P<.0001) or healthy controls (median [IQR], 54 [23–112] nmol/L; P<.0001). Moreover, alkylresorcinol concentrations in CD patients significantly decreased after introduction of a GFD (median, 34 nmol/L at diagnosis vs. 5 nmol.L after GFD, p=0.02). In the mice, median (IQR) total alkylresorcinol concentrations in serum samples of mice fed lifelong with a gluten‐free chow was 1.8 (1.6–2.3) nmol/L, which was further significantly increased to 16 (11–22) nmol/L after 8 days of feeding with the gluten free chow that had gluten added to it. (p=.008).ConclusionSerum alkylresorcinol concentrations could be a useful marker for dietary gluten in CD.Support or Funding InformationNo funding to report.
Differences in Nutritional Intake and Bone Health Among Adults With and Without Celiac Disease: Data From The National Health and Nutrition Examination Survey, 2009–2012
Authors: Habel Lara , Frankenfeld Cara L. , Gallo Sina , Moshfegh Alanna J. , Slavin Margaret 
Published: November 2023

BackgroundCeliac disease is a gastrointestinal malabsorptive disorder characterized by intestinal villous atrophy and triggered by an autoimmune response to gluten, leading to malnutrition and secondary conditions including osteoporosis. There is still a scarcity of information on the nutritional intake of adults with celiac disease as it relates to their bone health.ObjectiveTo evaluate differences in nutritional intake of calcium, vitamin D, and phosphorus; serologic concentrations of these nutrients; and bone health among adults with and without celiac disease.DesignCross‐sectional data was retrieved from the National Health and Nutrition Examination Survey (NHANES) cycles 2009–10 and 2011–12. Data including self‐reported dietary and supplement intake from 24‐hour recalls, serologic nutrient status, and dual x‐ray absorptiometry (DXA) scans were collected from 34 serologically positive (EMA+) adults with celiac disease. The participants were an average age of 43 years old (range 20–74 years). Results were compared with those of 9,496 control subjects using multiple linear regression modelling controlled for age, sex, and race/ethnicity.ResultsAdults with celiac disease consumed significantly more total calcium (Ca) and phosphorus (P) than the control group (1514 mg Ca/day vs. 1165 mg Ca/day, p = 0.008, and 1726 mg P/day vs. 1429 mg P/day, p = 0.022). They had significantly higher serum phosphorus concentrations than the controls (4.0 vs. 3.7 mg/dL, p = 0.008). No differences in serologic concentrations of calcium or 25(OH)D were identified. Lower bone mineral density (BMD) of the femoral neck was found in the adults with celiac disease than the controls (0.768 g/cm2 vs. 0.834 g/cm2, p = 0.049).ConclusionDespite greater overall calcium and phosphorus intake, adults who tested positive for celiac disease (EMA+) had lower overall bone mass than adults without celiac disease.
Decreased Blood Lactate Concentration with Twenty‐Eight Days of Mushroom Blend Supplementation
Authors: Dudgeon Wes , Thomas D. David , Dauch William , Scheett Timothy 
Published: November 2023

ObjectiveDietary supplement research in animal models has suggested various strains of mushrooms, specifically Cordyceps militaris, can improve physical performance. In this study our aim was to to determine the effects of the commercially available supplement Peak O2 (Compound Solutions, USA), a blend of six mushrooms which includes Cordyceps militaris, on indices of maximal and submaximal aerobic performance following 14 and 28 days of supplementation.MethodsTwenty‐three individuals (Mean ± standard deviation, Age = 21.4 ± 2.1 yrs, Height = 170.3 ± 7.7 cm, Body Mass = 70.8 ± 12.2 kg) participated in this randomized, blinded, placebo‐controlled study. The treatment group (M, n=12) was given 2.0 g·day−1 of mushroom blend with Gatorade (2.0 g) for flavor enhancement while the placebo group (P, n=11) received 2.0 g·day−1 color‐matched flour with Gatorade (2.0 g) for 28 days. A graded maximal cycle ergometer test was used to evaluate maximal oxygen consumption (VO2max), time to exhaustion (TTE) and heart rate recovery (HRr). The second stage of this protocol was maintained for five minutes (economy phase) to allow subjects to reach true steady state and submaximal oxygen consumption (VO2) and blood lactate concentration (BL) were assessed at the conclusion of this phase prior to subjects progressing to the next phase. Testing was conducted following 14 and 28 days of supplementation.ResultsDependent measures t‐tests were used to evaluate changes within groups compared to baseline values. There were no changes in VO2max or TTE for either group. During the economy phase, BL decreased significantly in M after 14 days (p = 0.03) when compared to baseline and 28 days (p = 0.02) of supplementation (baseline: 2.50 ± 0.59 mmol·L−1, 14 days: 2.39 ± 0.50 mmol·L−1, 28 days: 2.21 ± 0.54 mmol·L−1). There were no changes in BL economy in the P group (pre 2.29 ± 0.7 mmol·L−1, mid 2.21 ± 0.3 mmol·L−1, post 2.32 ± 0.7 mmol·L−1).ConclusionThese data suggest that twenty‐eight days of supplementation with 2.0 g·day−1 of Peak O2 may lower blood lactate concentration at submaximal intensity in young, apparently healthy individuals. The results offer the possibility that Peak O2 supplementation may decrease anaerobic metabolic stress during submaximal aerobic exercise.Support or Funding InformationPartial support for this work was provided by Disruptive Nutrition, LLC.
Dose‐response Effects of Soybean Oil in Salad Dressing upon the Bioavailability of Carotenoids/Fat‐soluble Vitamins in Salad Vegetables
Authors: White Wendy S , Zhou Yang , Crane Agatha , Dixon Philip , Quadt Frits , Flendrig Leonard M 
Published: November 2023

Research is needed to quantify the dose effect between added vegetable oil and carotenoid/fat‐soluble vitamin absorption from vegetables. The objectives were to evaluate the dose‐response relation between the amount of soybean oil in salad dressing and the absorption of: 1) carotenoids, phylloquinone, and tocopherols in salad vegetables; 2) retinyl palmitate formed from the provitamin A carotenoids, α‐ and β‐carotene. Women (n = 12) each consumed 5 equivalent salads containing grated carrots, cherry tomatoes, romaine lettuce and spinach. The salads with salad dressings containing 0, 2, 4, 8, or 32 g phylloquinone‐ and tocopherol‐stripped soybean oil were consumed in randomly assigned order and separated by ≥ 2 wk. The plasma chylomicron fraction was isolated from blood samples collected at baseline and 2, 3.5, 5, 7, and 9.5 h postprandially. Across the entire 0 – 32 g range, the amount of soybean oil in salad dressing was linearly related to the plasma chylomicron area under the curve (AUC) values for α‐carotene, lycopene, phylloquinone, and retinyl palmitate. Across a more limited 0 – 8 g range of soybean oil, there was a linear increase in the chylomicron AUC values for β‐carotene. The absorption of all carotenoids and fat‐soluble vitamins was highest with 32 g ingested oil (P < 0.002). For the carotenoids/fat‐soluble vitamins that showed a linear response, the slope β (soybean oil effect) varied widely between subjects. In conclusion, soybean oil in salad dressing promoted the absorption of all carotenoids and fat‐soluble vitamins from salad vegetables. For a large salad, maximal absorption required more than 8 g and up to 32 g or more of soybean oil. Linear models could be used to predict the relation between the amount of soybean oil and the absorption of α‐ and β‐carotene, lycopene, and phylloquinone, as well as that of the provitamin A conversion product, retinyl palmitate.Support or Funding InformationSupported by Unilever R&D, Vlaardingen, the Netherlands
Mesenchymal Stem Cell Exosome Treatment Restores Lung Architecture and Ameliorates Pulmonary Hypertension Associated with Bronchopulmonary Dysplasia
Authors: Willis Gareth R , Fernandez‐Gonzalez Angeles , Vitali Sally H , Liu Xianlan , Mitsialis S Alex , Kourembanas Stella 
Published: November 2023

BackgroundWith no effective treatment to prevent or reverse bronchopulmonary dysplasia (BPD), a multifactorial chronic lung disease of preterm infants, the need for new therapies is urgent. Mesenchymal stem cell (MSC)‐based therapies have shown promise in numerous preclinical models of lung pathologies relevant to neonatology. We have shown that the therapeutic capacity of MSCs is comprised in their secretome, and our recent studies have demonstrated that the therapeutic vector is represented by the exosomes (extracellular vesicles; EVs) they release. Here, we aimed to purify and comprehensively characterize MSC‐EVs from both human bone marrow (BMSC) and umbilical cord Wharton's jelly (WJ) and investigate the efficacy of MSC‐EV treatments in BPD.MethodsEVs in conditioned media were isolated by density on iodixanol gradient and characterized by electron microscopy, nanoparticle tracking analysis and western blot. Proteomic profiling was obtained by LC‐MS. Immunomodulatory capacity of MSC‐EVs was assessed by an in vitro macrophage polarization assay. Newborn FVB mice were exposed to hyperoxia (75% O2) for 7 days (postnatal day (PN) 1–7). At PN 4 mice were treated with a bolus intravenous dose of purified MSC‐EVs or human dermal fibroblast‐EVs (HDF‐EVs). After hyperoxic exposure the mice were placed in room air for one to five weeks. Histological analysis of lungs harvested at PN 14 and PN 42 was performed to assess alveolar injury, blood vessel number and vascular remodeling. At PN 42, right ventricular systolic pressure (RVSP) and right ventricular hypertrophy were assessed and pulmonary function tests were conducted.ResultsEVs immunoblots were positive for CD9, TSG101 and Alix. Proteomic profiling of WJMSC‐EVs and HDF‐EVs detected species unique or differentially enriched in MSC‐EVs. In vitro, addition of MSC‐EVs to alveolar macrophages (MH‐S cell line) significantly reduced the induction of M1 markers such as TNFα and CCL5. Hyperoxia‐exposed mice exhibited a significantly higher mean linear intercept compared to normoxic controls or to hyperoxia‐exposed mice treated with either BMSC‐EVs or WJMSC‐EVs, whereas HDF‐EV treatment had no beneficial effect on lung architecture. Hyperoxia‐exposed mice exhibited elevated RVSP compared to normoxic control mice, which was effectively reduced by treatment with BMSC‐EVs or WJMSC‐EVs.ConclusionWe show that a bolus dose of purified human MSC‐EVs, from two different MSC sources effectively alleviates core features of hyperoxia‐induced BPD, drastically improving lung development and associated pulmonary hypertension, providing a novel platform for a new therapeutic intervention in newborn cardio‐respiratory diseases.Support or Funding InformationThis work was supported by NIH grant #RO1 HL085446 and United Therapeutics Sponsored Research
Maternal obesity programs offspring gut microbiome and liver disease in a sexually dimorphic manner
Authors: Wankhade Umesh D , Zhong Ying , Kang Ping , Chintapalli Sree V , Andres Aline , Thakali Keshari M , Shankar Kartik 
Published: November 2023

Maternal obesity programs offspring weight gain and predisposition to metabolic syndrome. However, sexual differences in developmental programming are poorly understood. Here we employed a mouse model where female dams were fed either control (17% fat) or high‐fat diets (HFD, 45% fat calories) 12 wk prior to conception and then through weaning. Male and female offspring were provided ad libitum access to either control or HFD for 14 wk beginning at 4 wk of age, during which body weights were monitored weekly. At 18 wk of age hepatic histology was assessed and cecal contents were snap frozen for microbiome analysis. Male offspring gained more body weight than either control or HFD females (p<0.001). Two‐way ANOVA showed a significant effect of diet (p<0.01–0.001) and sex (p<0.001) when offspring were fed HFD. Hepatic histology also showed more severe fatty liver in male offspring relative to females. Pro‐inflammatory cytokines in serum such as IL1b, IL‐2, and IL‐6 were higher in male offspring fed HFD (p<0.05), whereas anti‐inflammatory IL‐5 was lower (p<0.001). Microbial community profiling via 16S rRNA amplicon sequencing showed that overall a‐diversity was lower in females (p<0.05) and in offspring from HFD dams (p<0.05). Two‐way ANOVA showed a significant effect of diet (p<0.001) and sex (p<0.001) on Bacteroidetes and Firmicutes when offspring were fed HFD. Enrichment of Firmicutes in males and Lactococcus, Anaerotruncus and Ruminococcus genera in female offspring were found using LefSe. When offspring were fed HFD, Bacteroidetes were lower and Firmicutes were higher in males (p<0.01). Multivariate association with linear models showed correlation between overall weight gain and abundance of families Lachnospiraceae and Clostridiaceae. Further, functional prediction using PiCRUST showed that bile acid synthesis, immune and bacterial response, protein digestion and cell cycle regulation pathways were enriched when offspring were fed HFD. Importantly, sex differences in functional categories were more pronounced by post‐weaning HFD. In conclusion, our findings suggest that prenatal HFD feeding alters hepatic steatosis and microbiome in offspring, and shows sexually dimorphic differences in response to post‐weaning HFD. Supported by USDA CRIS Project 6206‐51000‐010‐05S.Support or Funding InformationUSDA CRIS 6206‐51000‐010‐05S
High fat diet‐induced biliary lipoapoptosis, senescence, hepatic steatosis and fibrosis are reduced in secretin receptor knockout (SR−/−) mice
Authors: Kennedy Lindsey Leann , Wu Nan , Venter Julie , Meng Fanyin , Francis Heather , Zhou Tianhao , Glaser Shannon , Alpini Gianfranco 
Published: November 2023

BackgroundNonalcoholic fatty liver disease (NAFLD) is derived from simple steatosis, and can develop to nonalcoholic steatohepatitis (NASH) if left untreated. Recently, a cholestatic variant of NAFLD in patients has been identified as having portal inflammation and ductular reaction. Free fatty acids (FFAs) are increased in the serum of NAFLD patients and can induce lipoapoptosis. We have shown that the secretin/SR axis stimulates liver fibrosis, and it has been indicated that secretin can influence FFA uptake in adipocytes. Based on these data we aimed to evaluate the effect of SR−/− on biliary lipoapoptosis, senescence, hepatic steatosis and fibrosis following high fat diet (HFD) feeding.MethodsWT and SR−/− mice were fed beginning at 4 weeks of age either control diet (CD) or HFD with a high fructose corn syrup equivalent for 20 weeks. Liver and serum were obtained, and cholangiocytes were isolated by laser capture microdissection. Hepatic steatosis and inflammation were evaluated by H&E and Oil Red O staining. Lipid metabolism was evaluated in total liver and cholangiocytes by qPCR for peroxisome proliferator activated receptor‐α (PPAR‐α), and the PPAR‐α‐dependent enzymatic genes carnitine palmitoyl‐transferase 1α (CPT1α) and long chain Acyl CoA synthetase (ACSL1). Lipoapoptosis was detected by TUNEL staining and qPCR for Bax in cholangiocytes. Senescence was examined by SA‐β‐gal staining in liver sections and qPCR for p18 and p21 in total liver and cholangiocytes. Liver fibrosis was measured by Sirius red staining and qPCR for TGF‐β1 and collagen‐1a in total liver. In vitro, control or shRNA‐SR transfected murine cholangiocytes were treated with 800 μM of FFAs (palmitate, stearate or oleate) added to FFA‐free media for 24 hr before evaluating lipoapoptosis and senescence.ResultsWT HFD mice had increased hepatic steatosis and inflammation, but this was significantly reduced in HFD SR−/− mice. Total liver and cholangiocytes from HFD WT mice had increased expression of PPAR‐α, CPT1α and ACSL1, but these lipogenesis markers were decreased in HFD SR−/− mice. Biliary lipoapoptosis, senescence and liver fibrosis were increased in HFD WT mice; however, these parameters were decreased in HFD SR−/− mice. In vitro, FFAs induced biliary lipoapoptosis and senescence gene expression in murine cholangiocytes, but this FFA‐induced injury was reduced in murine cholangiocytes transfected with shRNA‐SR.ConclusionKnockout of SR decreases PPAR‐α signaling in cholangiocytes, thereby decreasing lipogenesis. Furthermore, knockout of SR decreases HFD‐induced biliary lipoapoptosis, senescence, hepatic steatosis and fibrosis. Modulation of secretin/SR signaling may be a therapeutic option for patients suffering from NASH.