bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unlike Adipokines, Insulin Concentrations in Human Milk Surpass those in Maternal Circulation, are Higher among Overweight Women, and are Associated with Maternal Insulin Resistance
Authors: Young Bridget E , Westcott Claire , Chartier‐Logan Catherine , Hernandez Teri , Barbour Linda , Friedman Jed , Krebs Nancy F 
Published: November 2023

The impact of maternal weight status and insulin sensitivity on bioactive components in human milk (HM) remains poorly understood and may have clinical ramifications on the breastfeeding infant. Breastfeeding mother/infant pairs (n=26 normal weight (NW) and n=23 overweight/obese (OW/Ob) mothers) were followed over the first 4 months of lactation. Fasting HM and maternal blood samples were collected at 2‐weeks and 4‐months postpartum. Insulin, leptin, and adiponectin were measured. Maternal HOMA‐IR was calculated from fasting serum insulin and glucose.Insulin and leptin concentrations were higher in HM of OW/Ob women at 2‐weeks (p<0.05) but only leptin remained higher at 4‐months (p<0.0001). Both HM adiponectin and leptin were significantly lower than maternal concentrations (p<0.0001). Both leptin and adiponectin in HM were positively correlated with maternal serum concentrations at 2‐weeks and 4‐months (p<0.02), but only leptin showed a consistent correlation with maternal BMI at each time point.In contrast, HM insulin was 98% higher than maternal serum insulin at 2‐weeks (p<0.0001) and 32% higher at 4‐months (p<0.001). This difference held among NW (p<0.01) and OW/Ob (p=0.05) mothers separately and at each time‐point. HM insulin at 2‐weeks was positively related to maternal BMI at 2‐weeks (p=0.017, R2=0.12, n=48), but more strongly related to markers of maternal insulin resistance: fasting maternal insulin (p<0.0001, R2=0.42, n=32) and HOMA‐IR (p<0.0001, R2=0.49, n=32). At 4‐months, HM insulin remained positively related to concurrent maternal BMI (p=0.032, R2=0.12, n=40) but remained more strongly correlated with fasting maternal insulin (p<0.001, R2=0.29, n=38) and HOMA‐IR (p<0.0001, R2=0.37, n=38).This study was unique in its concurrent assessment of insulin, measured in a fasting state, in both HM and maternal circulation. The potential roles of HM leptin and adiponectin on appetite and growth of the breastfed infant has been previously postulated. The demonstrated elevated concentrations of insulin in HM represent a large exposure of this powerful, appetite suppressing, and anabolic hormone to the breastfeeding infant. This enteral exposure may be especially critical early postpartum when intact hormones in HM can be absorbed directly into the bloodstream. Maternal insulin sensitivity may play a role in regulation of HM insulin concentrations. Infant ramifications of chronic exposure to high concentrations of dietary insulin need to be researched.Support or Funding InformationUniversity of Colorado CCTSI UL1 RR025780; NIH‐NICHD F32‐HD0978068; NIH‐NIDDK K24‐DK083772 & T32‐DK007658‐21; Center for Women's Health Research Young Investigator Award; Thrasher Research Fund Early Career Award
Maternal high‐fructose in pregnancy adversely affects morphological aspects of the placenta
Authors: Song Aleida , Astbury Stuart , Hoedl Abha , Coursen Nicole , Dixon Walter , Hemmings Denise , Bell Rhonda 
Published: November 2023

BackgroundWe have previously reported that pregnant rats fed a high fructose solution developed insulin resistance and hypertriglyceridemia, and that their offspring were smaller at birth than offspring from control (CONT) dams. However, there has been relatively little information about how fetal restriction can be induced by maternal fructose intake and how this leads to increased risks for developing diseases in offspring later in life. We focused our work on the placenta as a key organ to regulate fetal growth since placenta is an important determinants of nutrient supply for the fetus. Therefore, this study examined the effects of high fructose intake on adhesion molecule and nutrient transporter gene expression and morphological features of the placenta at term.MethodsFemale rats received either a 10% fructose solution (Fr, n=9) or distilled water (CONT, n=8) for 3 weeks prior to and during pregnancy. On gestational day 21, placentae and fetuses were dissected free from the uterus, weighed and the ratio of placental:fetal weight was calculated. Three placentae from each rat dam were used to determine total mRNA expression of glucose transporter 1 (GLUT1), fatty acid binding protein1 (FABP1), sodium‐coupled neutral amino acid transporter 2 (SNAT2), vascular endothelial growth factor (VEGF), placental growth factor (PLGF), vascular endothelial growth factor receptor 1 and 2 (VEGFR1, VEGFR2). GAPDH was used as a housekeeping gene. Another three fixed placentae were stained by in situ hybridization and measured for GLUT1 expression between labyrinth zone(LZ)/junctional zone(JZ). P<0.05 was considered statistically significant.ResultsFetal weights at gestational day 21 were reduced in the Fr vs. CONT group (Fr=3.38±0.13, CONT=3.86±0.16 g, p<0.05), although the fetal:placental weight ratio did not differ between groups. Total (relative) mRNA expression of VEGFR1 and VEGFR2 was significantly lower in the placentae from Fr vs CONT (VEGFR1, Fr=0.93±0.06, CONT=1.13±0.07; VEGFR2, Fr=0.98±0.15, CONT=1.66±0.13, p<0.05 for both). The GLUT1 mRNA ratio between LZ/JZ was lower in Fr than in CONT (Fr=17.19±2.1, CONT=31.06±5.97, p<0.05). Total mRNA expression of VEGF, PLGF, FABP1 and SNAT2 were not different between groups.ConclusionHigh fructose intake reduced the expression of glucose transporters in the placenta and reduced the expression of adhesion molecules with important angiogenic properties. These changes were associated with lower birth weight of the fetus. Such changes to the placenta may contribute to poor fetal growth and developmental programming of the offspring associated with increased risk for metabolic disorders in later life.Support or Funding InformationNSERC, Faculty of Medicine & Dentistry, University of Alberta
Consequences of Maternal Iron‐Deficiency: Fetal Anemia, and Hypoxia in Select Tissues of the Conceptus
Authors: Woodman Andrew , Mansour Yael , Bourque Stephane 
Published: November 2023

Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide, and affects populations across the socio‐economic spectrum. The incidence of ID anemia in pregnant women is of chief concern, with rates as high as 80 % in developing countries, and a prevalence of 23 % in Canada. Maternal ID during pregnancy has been shown to impact fetal iron status and growth trajectories, although the precise mechanisms underlying this intrauterine growth restriction are unknown. We hypothesized that maternal ID causes fetal hypoxia, resulting in asymmetric growth restriction in more severe ID. Female rats (initial age 6 weeks for severe (S‐ID), 9 weeks for moderate (M‐ID)) were fed iron restricted diets throughout pregnancy. Dams were treated with pimonidazole on gestational day (GD)20 to assess hypoxia (<10 mm Hg O2). Maternal and fetal hemoglobin (Hb) levels and body weights were assessed on GD21. Pup organs were excised and weighed to assess degree of asymmetric growth restriction. Tissue immunofluorescence was carried out on GD21 pup tissues with fluorescent probes to detect covalent pimonidazole adducts. Both M‐ and S‐ID groups caused fetal anemia ( fetal Hb reduced 30.9 % and 63.8 %, respectively, compared to control of 9.27 g/dL, P<0.01), despite only S‐ID dams becoming anemic (reduction in Hb 10.9 % and 50.3 % for M‐ and S‐ID, respectively, compared to 13.60 g/dL control Hb, P<0.001). Both M‐ and S‐ID caused fetal growth restriction (reduced weight by 9.1 % and 34.9 %, respectively, compared to control weight of 5.45 g, P<0.001). S‐ID, but not M‐ID, caused asymmetrical growth restriction, wherein relative heart and brain weights increased (60 % and 9.8 %, respectively, compared to control weights of 0.005 g/g and 0.041 g/g, P<0.01), and kidney and liver size decreased (20 % and 15 %, respectively, compared to control weights of 0.005 g/g and 0.067 g/g, P<0.01). M‐ID was associated with increased staining for pimonidazole in fetal livers (P=0.01) and kidneys (P=0.01), but not in brains and placentae, versus respective controls; hypoxia staining is S‐ID fetuses is ongoing. Fetal anemia and growth restriction can occur in the absence of maternal anemia, emphasizing the need for new methods of assessment in the clinical setting. Elucidation of the mechanisms through which ID impacts fetal growth and development will enable us to develop a platform with which we can test novel therapeutics.Support or Funding InformationAW held an Alberta Innovates Health Solutions Summer Studentship. SB Holds grants from the Canadian Institute of Health Research (CIHR), and the Women and Children's Health Research Institute (WCHRI).
The Effect of Oat Beta‐Glucan on Clinical Lipid Markers for Cardiovascular Disease Risk Reduction: A Systematic Review & Meta‐Analysis of Randomized Controlled Trials
Authors: Ho Hoang Vi Thanh , Sievenpiper John L , Zurbau Andreea L , Mejia Sonia Blanco , Jovanovski Elena , Yeung Fei Au , Jenkins Alexandra L , Vuksan Vladimir 
Published: November 2023

BackgroundOats are a rich source of β‐glucan, a viscous soluble fibre recognized for its cholesterol lowering properties, and are associated with reduced risk of cardiovascular disease.ObjectiveTo conduct a systematic review and meta‐analysis of RCTs investigating the cholesterol lowering potential of oat β‐glucan on LDL‐C, non‐HDL‐C, and apoB, for the risk reduction of cardiovascular disease.DesignMEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials were searched. We included Only RCTs of ≥ 3 weeks duration assessing the effect of diets enriched with oat β‐glucan compared with controlled diets on LDL‐C, non‐HDL‐C, or apoB. Two independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using the generic inverse variance method with random effects models and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed by the Cochran Q statistic and quantified by the I2 statistic.Results58 trials (N = 3952) were included in the final analysis. A median dose of 3.5 g/day of oat β‐glucan significantly lowered LDL‐C (MD = −0.19 mmol/L [95% CI: −0.23, −0.14] P < 0.00001) non‐HDL‐C (MD = −0.20 mmol/L [95% CI: −0.26, −0.15] P < 0.00001) and apoB (MD = −0.03 g/L [95% CI: −0.05, −0.02] P < 0.0001) compared to control interventions. There was evidence of considerable unexplained heterogeneity in the analysis of LDL‐C (I2 = 79%) and non‐HDL‐C (I2 = 99%).ConclusionPooled analyses show that oat β‐glucan have a lowering effect on LDL‐C, non‐HDL‐C, and apoB. Inclusion of oat containing foods may be a strategy for achieving targets in cardiovascular disease reduction.
Effects of polyphenolic‐rich dark chocolate and almonds on cardiovascular risk factors in overweight and obese adults
Authors: Lee Yujin , Berryman Claire , West Sheila , Chen C.‐Y. Oliver , Blumberg Jeffrey , Preston Amy , Lapsley Karen , Fleming Jennifer , Kris‐Etherton Penny 
Published: November 2023

Chocolate is a source of flavanols and has been shown to reduce the risk of cardiovascular disease (CVD) via beneficial effects on vascular health. Almonds are high in unsaturated fat and bioactive compounds that have been shown to favorably affect multiple CVD risk factors. The objective of this study was to evaluate the individual, additive, and synergistic effects of dark chocolate/natural cocoa and almonds on CVD risk factors. Thirty‐one participants [age (mean ± SD): 46 ± 10 y; BMI (in kg/m2): 29.6 ± 2.8; 13 women; 18 men] were randomized to a 4 period crossover, controlled feeding study. All participants consumed each of the 4 diets for 4 weeks. The 4 diets were: Average American diet (AAD: 49% CHO, 17% PRO, 34% FAT, 13% SFA, 276 mg/d CHOL, no almonds or dark chocolate/cocoa), Almond diet (ALD: 49% CHO, 16% PRO, 35% FAT, 8% SFA, 153 mg/d CHOL, 1.5 oz. almonds/d), Chocolate/cocoa diet (CHOC: 53% CHO, 16% PRO, 32% FAT, 11% SFA, 157 mg/d CHOL, 43 g dark chocolate/d, 11 g natural cocoa/d), and Chocolate/cocoa + Almond diet (CHOC + ALD: 50% CHO, 16% PRO, 34% FAT, 8% SFA, 116 mg/d CHOL, 43 g dark chocolate/d, 11 g natural cocoa/d, 1.5 oz. almonds/d). Results from twenty‐six participants are reported; the study will be completed in December, 2015. Compared to baseline, the ALD and CHOC + ALD diets decreased total cholesterol (−15.6 ± 3.1 mg/dL, P < 0.001; −10.2 ± 3.1 mg/dL, P < 0.01, respectively) and LDL‐C (−11.9 ± 2.7 mg/dL, P < 0.001; −9.0 ± 2.7 mg/dL, P < 0.01, respectively). Compared with the AAD diet, the ALD diet demonstrated greater reductions in total cholesterol (−10.6 ± 2.9 mg/dL, P < 0.01) and LDL‐C (−11.3 ± 2.9 mg/dL, P < 0.01). Compared to baseline, CHOC and CHOC + ALD diets increased HDL cholesterol (2.20 ± 0.97 mg/dL, P = 0.03; 2.86 ± 0.97 mg/dL, P < 0.01, respectively). Compared with the AAD diet, the CHOC + ALD had a greater increase in HDL‐C (2.56 ± 0.97 mg/dL, P < 0.05). The ALD, CHOC, and CHOC + ALD diets improved fasting plasma insulin (−1.50 ± 0.58 mU/L, P = 0.01; −1.45 ± 0.58 mU/L, P = 0.02; −1.25 ± 0.58 mU/L, P = 0.04, respectively) and insulin resistance (via the homeostasis model assessment of insulin resistance: −0.38 ± 0.16, P = 0.02; −0.32 ± 0.16, P = 0.06; −0.30 ± 0.16, P = 0.07, respectively). The ALD diet significantly lowered fasting glucose (−1.69 ± 1.28 mg/dL) compared with the CHOC diet (2.12 ± 1.28 mg/dL, P < 0.01) and CHOC + ALD diet (1.50 ± 1.28 mg/dL, P < 0.05). Our results demonstrate that the individual and combined consumption of dark chocolate/cocoa and almonds improved multiple CVD risk factors including lipid profile and insulin resistance. This trial was registered at the ClinicalTrials.gov as NCT01882881.Support or Funding InformationThis study was supported by the Hershey Company and the Almond Board of California
Role of Hypoxia‐Inducible Factor (HIF) on colonic goblet cell differentiation and function during mucosal healing
Authors: Whitney Alyssa K , Schwisow Kalya D , Bayless Amanda J , Golden‐Mason Lucy , Mehta Gaurav , Kuhn Kristine A , Colgan Sean P , Campbell Eric L 
Published: November 2023

Secreted mucus is essential for intestinal homeostasis, separating luminal bacteria from the colonic epithelium and preventing inappropriate inflammation. Depletion of the mucus‐secreting goblet cells has been shown in mice to lead to development of spontaneous colitis. Treatment of mice with a prolyl hydroxylase inhibitor (AKB‐4924) leads to stabilization of hypoxia inducible factor‐1 alpha (HIF‐1α) and ultimately regulation of hypoxia‐responsive genes that promote mucosal protection. Interestingly, goblet cell hyperplasia was observed following in vivo administration of AKB‐4924, which may account for the mucosal protection observed. Thus, we hypothesized epithelial stabilization of HIF‐1α leads to goblet cell differentiation and hyperplasia within the GI tract.Utilizing a three‐dimensional murine intestinal stem cell spheroid culture system, we were able to analyze the influence of HIF‐1α stabilization on epithelial differentiation in a physiologically relevant context. Spheroids were treated with a goblet cell promoting factor (a gamma secretase inhibitor, DBZ), AKB‐4924 or hypoxia and analyzed by qPCR for changes in differentiation markers for secretory goblet cells (i.e. Atoh1, Muc2, and SPDEF) or absorptive enterocytes (i.e. Hes1, ALPI, and Fabp2). Additionally, DBZ and AKB‐4924 treated organoids were visualized using immunofluorescence for changes in the expression of Muc2, the predominant colonic mucin. Contrary to our hypothesis, neither AKB‐4924 nor hypoxia resulted in the induction of goblet cell differentiation factors. Furthermore, mice lacking HIF‐1α in the intestinal epithelium (HIF‐1αfl/fl‐VillinCRE) exhibited normal colonic goblet cell numbers. However, goblet cells in mice lacking epithelial HIF‐1α appeared less organized with mucin granules less uniform in size and more randomly dispersed, and have a significantly altered expression profile of both secreted and adherent mucins, indicating that epithelial HIF‐1α is involved in goblet cell function.Therefore, we conclude that AKB‐4924 does not act directly on the epithelium to promote epithelial goblet cell differentiation, however, epithelial HIF‐1α does alter goblet cell function, potentially regulating intestinal mucus layer, which may contribute to the mucosal‐protective role for stabilized HIF.Support or Funding InformationR01 DK103639 from NIDDK, CDA from Crohn's and Colitis Foundation of America to E.L.C.
Hunger and satiety responses to saturated fat‐rich meals before and after a high PUFA diet
Authors: Cooper Jamie A , Stevenson Jada L , Paton Chad M 
Published: November 2023

ObjectiveHigh‐fat meals rich in poly‐unsaturated fats (PUFAs) have been shown to induce greater satiety than meals rich in saturated (SFA) or mono‐unsaturated (MUFA) fats in an acute setting. It remains unknown, however, what the long‐term diet effects of PUFAs are on hunger and satiety.PurposeTo determine hunger and satiety responses to high SFA test meals before and after a 7‐day high PUFA diet.MethodsEighteen, normal weight, sedentary adults (BMI=21.4±2.3kg/m2; age=22.7±4.1y) were randomly assigned to either a PUFA or control diet. Following a 3‐day lead‐in diet, participants reported for the baseline visit where anthropometrics and a fasting blood sample were collected. Participants then consumed two high‐fat meals (breakfast and lunch) that were rich in SFAs (47% of total energy as SFA). Postprandial blood draws were collected approximately every 30 minutes for 4 hour after each HF meal, for a total of 8 hours. Participants then consumed a high PUFA diet (50% carbohydrate, 15% protein, 35% fat, of which 21% of total energy was PUFA,) or control diet (50% carbohydrate, 15% protein, 35% fat, of which 7% of total energy was PUFA) for the next 7 days. All food and drink were provided by research personnel, and diets were designed to meet each participants estimated daily energy needs. Following the 7‐day diet, participants completed the post‐visit which included same procedures as the baseline visit (2 high SFA meals and 8 hours of blood draws). Blood samples were analyzed for ghrelin (hunger hormone) and Peptide YY (PYY), insulin, and leptin (satiety hormones).ResultsFor fasting concentrations, the PUFA group showed a significant decrease in ghrelin (1147.1±101.4 vs. 967.0±85.9pg/mL, p<0.05) and significant increase in PYY (89.2±9.3 vs. 113.5±11.8pg/mL, p<0.05) from pre‐to post‐diet. There were no change in fasting insulin or leptin concentrations, or in the control group for any hormone. In response to the high SFA meal challenges, there was greater postprandial PYY after the 7‐day high PUFA diet (postprandial average of 140.8±10.4 vs. 150.6±8.8pg/mL for pre‐ to post‐PUFA diet, respectively; p=0.05). Conversely, there were no significant differences in the postprandial response for ghrelin, insulin, leptin, or VAS measures from pre‐ to post‐diet in either the PUFA or control groups (ns).ConclusionA high PUFA diet consumed for seven days favorably altered physiological markers of hunger and satiety in the fasted and fed state. This study is the first to show that the types of fat consumed on a daily basis can alter long‐term appetite hormone profiles.Support or Funding InformationThis study was funded by the California Walnut Commission.
Application of the Evidence Review Cycle Model to Review Food and Health Evidence to Inform Canadian Dietary Guidance Decision‐Making
Authors: Lowell Hélène , Ellis Ann , Colapinto Cynthia K 
Published: November 2023

Canada's population‐level dietary guidance policies and education tools are used by health professionals, policy makers and academics to support nutrition policies, programs and research. While Health Canada has always reviewed the evidence base, the growing volume of nutrition related research stimulated Health Canada to develop the Evidence Review Cycle (ERC) for dietary guidance, a model that formalizes the evidence review process. A Health Canada review of reports on food topics in relation to nutrition‐related chronic diseases and conditions will be described to illustrate the implementation of the ERC model in Canada to support decision‐making for dietary guidance policy.Reports published between 2006 and July 2015 by leading scientific organizations or Federal agencies, as well as health claims assessments from Health Canada, were reviewed. Reports were included if the organization involved an expert committee, systematically reviewed evidence and an evidence grade supported the conclusions. Excluded conclusions were specific to populations less than 2 years of age or pregnant, were not original to the report or were commissioned by industry.A total of 693 conclusions were retained from 28 reports and 58 of these conclusions were graded as convincing (strong), which included those related to sodium and increased risk of high blood pressure, trans fatty acids and increased risk for cardiovascular disease, and dietary patterns—characterized by higher consumption of vegetables, fruits, whole grains, low‐fat dairy, and seafood, and lower consumption of red and processed meats, and lower intakes of refined grains, and sugar‐sweetened foods and beverages—and positive cardiovascular disease outcomes. Convincing evidence was also found on the relationships for isocaloric replacement of saturated fatty acids and cardiovascular disease outcomes, red and processed meat and colorectal cancer, and soy protein and lowered blood cholesterol.Food and health relationships are one important input in the broad range of considerations that assist Health Canada in developing population‐level dietary guidance. Guidance is also informed by evidence on stakeholder and Canadians use dietary guidance and by national‐level data on what Canadians are eating.