bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Obesity on Serum and Hepatic Cations in Zucker Rat Model
Authors: Hakkak Reza , Korourian Soheila , Niedoba Matthew , Romani Andrea
Published: November 2023

Obesity has been epidemic in the United States for more than two decades. Obesity is associated with type 2 diabetes, cardiovascular disease and certain types of cancer. We investigated the effect of obesity on serum and liver cations. Five‐week‐old female lean and obese Zucker rats were used. After one week of acclimation, Lean and Obese rats were maintained on AIN‐93 G diet for 155 days and serums and livers were collected. Different cations were measured by atomic absorbance spectrophotometry in addition to protein content. Obese rats gained significantly (P<0.001) more weight than lean rats. Obesity caused; 1) a significant increase in serum protein (P<0.05) but not in hepatic protein content, which was decreased (p<0.05); 2) a significant increase in total serum Ca2+ levels (p<0.05) but not in total hepatic Ca2+ content, which was significantly decreased (p<0.05); 3) a decreased in serum K+ level (P<0.05) but an increase in liver K+ content (p<0.05), and 4) a decrease in serum Mg2+ vs. an increase in liver Mg2+ content (p<0.05). As a consequence, the hepatic Mg2+/Ca2+ ratio in obese animals was three time higher as compared to the lean counterpart. In contrast, the Mg2+/Ca2+ ratio in the serum of the obese animals was about 25% lower as compared to the ratio in the lean animals. The effects of the obesity and these changes in cation content and Mg2+/Ca2+ ratio on the expression of key metabolic liver enzymes are currently under investigation. In summary, our results show that serum can be a good predictor of several intracellular cations levels compared to liver. The implications of these cation changes on liver metabolism and ER stress are in need of further clarification.

Support or Funding Information

(Supported by CUMG and ABI grants to RH).
The Association of Serum Biomarkers of Types 2 Diabetes with BMI
Authors: Stephen Laurie Lynn , Marshall Kristi , Damour Marc , Race Tori
Published: November 2023

Biomarkers of types 2 diabetes are often confounded by obesity. Here we examined 30 serum biomarkers associated with diabetes in 20 normal BMI, 20 overweight and 20 obese individuals. Each group consisted of 10 males and 10 females and the average age was 70 ± 10 years. Paranoxase‐1 (PON‐1) was negatively correlated to BMI (r=−0.44, p<0.005), whereas Galectin‐3 showed a positive correlation to BMI (r=0.3; p<0.05). VDBP and Hemopexin were both negatively correlated to BMI in the male group (r=−0.41; p<0.05 and r=0.62; p<0.0005 respectively). ANGPTL7, a novel serum pro‐ angiogenic serum protein was higher in the overweight and obese diabetics compared to the normal BMI group (4.1 vs 3.2 ng/ml; p<0.03), but was not correlated to BMI. ANGPTL7 was significantly correlated to Zinc‐Alpha‐2 Glycoprotein (ZAG) and Retinol‐Binding Protein‐4 (RBP‐4) (r=0.37 and r=0.29 respectively, p<0.0001). Complement C1q Tumor Necrosis related Proteins 1, 4 and 5 (CTRP‐1, CTRP‐4 and CTRP‐5) were not associated with BMI. CTRP‐1 was associated with soluble Leptin Receptor and Dipeptidyl‐Peptidase 4 (DPPIV), (r=0.48 and r=0.41 respectively; p<0.001). CTRP‐4 showed weak but significant correlations with ANGPTL7, CTRP‐1 AND PON‐1. CTRP‐5 serum levels were positively correlated to PON‐1 (R=0.42; P<0.001) and negatively correlated to DPPIV (r=−0.34; p<0.01). Our data shows that only 4 of the 30 diabetic biomarkers were influenced by BMI in the population of samples studied. This may differ in a younger cohort. The association of novel diabetic biomarkers with serum proteins that have been studied in more depth may lead to more information about their significance in serum.
Associations between dietary macronutrients, glucose and insulin dynamics in obese adolescents
Authors: Braun Ethan , Wagner Kelly , Armah Seth , Smith Lisa , Boushey Carol , Delp Edward , Hannon Tamara , Gletsu‐Miller Nana
Published: November 2023

Objective

Modifiable risk factors of type 2 diabetes (T2D) include dietary factors which impact glycemia, but there have been few investigations in adolescents. We aim to determine associations between diet and measures of glucose and insulin dynamics in adolescents who are obese.

Research Design and Methods

Cross‐sectional, baseline measures were obtained from an ongoing, randomized controlled intervention to prevent T2D in obese adolescents. Dietary intake was assessed for four days using mobile phone technology to create an electronic food record. Glucose and insulin dynamics were assessed during a 2‐hour oral glucose tolerance test. Multiple linear regression was used to assess the associations between macronutrient intake and measures of glycemia and insulin.

Results

Fifteen obese participants (67% female, BMI 34.9 kg/m2) were screened and 47% had prediabetes. Anthropometric measures were similar between youth with prediabetes and youth with normal glycemia. Dietary fat intake was associated with concentrations of glucose at 2 hours (β=1.3, P= 0.006), insulin sensitivity (β= −1.5, P= 0.002), and beta‐cell function (β= −1.6, P= 0.0009); total fiber intake was associated with concentrations of glycosylated hemoglobin (β= −0.57, P= 0.04).

Conclusions

Dietary intake of fat and fiber were associated with glucose and insulin action and may serve as targets for future interventions for prevention of T2D.

Support or Funding Information

This work was supported in part by a Project Development Team within the ICTSI NIH/NCRR Grant Number UL1TR001108. Other support included funding from Riley Hospital for Children Indiana University Health, and the Center for Pediatric Obesity and Diabetes Prevention Research.
Untargeted Metabolomic Profiles, Childhood Obesity, and Metabolic Risk in the ELEMENT Cohort
Authors: LaBarre Jennifer , Perng Wei , Karnovsky Alla , Tang Lu , Song Peter , Burant Charles F. , Cantoral Alejandra , Peterson Karen E. , Téllez‐Rojo Martha Maria
Published: November 2023

Objective

To use metabolomics data quantified on an untargeted platform to identify metabolic alterations associated with obesity during childhood, and to examine the relations of these metabolite patterns with conventional cardiometabolic biomarkers.

Methods

Untargeted metabolomic features were analyzed using liquid chromatography/mass spectrometry in fasting serum from 250 children enrolled in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project, a birth cohort study. ELEMENT participants aged 8–13 years were selected for this analysis based on availability of archived biomarkers in serum and cord blood required for a separate study. We used Principal Component Analysis (PCA) to consolidate 4652 metabolite features into factors based upon their inter‐correlations. To determine how obesity status corresponded with differences in circulating metabolites, we compared factors scores for obese (body mass index [BMI] z‐score ≥2; n=46) and normal weight (−2≤ BMI z‐score <1; n=119) children. Metabolite clusters associated with obesity were retained for further investigation. Among all participants, we used multiple linear regression to estimate the relationship between metabolite factor scores and conventional biomarkers of metabolic risk: high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol, triglycerides, fasting glucose, and leptin.

Results

Median age was 10.0 years; 47.6% were boys. Our sample included 46 obese (18.4%), 81 overweight (32.4%), 119 normal weight (47.6%), and 4 underweight children (1.6%). As compared to normal weight children, obese children had a higher score for Factor 2, which largely comprised of amino acids and modified fatty acids. After accounting for sex, maternal education, and pubertal stage, each unit increment in Factor 2 corresponded with 5.54 (95% CI: 2.18, 8.90) mg/dL higher total cholesterol, 4.25 (95% CI: 1.51, 7.00) mg/dL higher LDL, and 6.43 (95% CI: 0.94, 11.93) mg/dL higher triglycerides.

Conclusions

In this sample of peripubertal Mexican children, an amino acid and modified fatty acid metabolite pattern associated with obesity was also related to an adverse lipid profile. Future longitudinal studies are warranted to ascertain temporality.
Implications of Taste Receptor Polymorphisms in Dietary Interventions: TAS2R38 Polymorphisms Associate with Changes in Vegetable Intake
Authors: Schisler Jonathan C. , Calancie Larissa , Lenhart Kaitlin , Keyserling Thomas , Gizlice Ziya , Patterson Cam , Ammerman Alice
Published: November 2023

Few Americans meet consumption recommendations for dark green and orange vegetables that are strongly associated with reduced risk of chronic diseases. The ability to detect propylthiouricil, or PROP, is linked to vegetable preference and frequency of vegetable consumption. The TAS2R38 gene encodes a g‐protein coupled receptor that binds PROP and phenylthiocarbamide (PTC). Both PROP and PTC resemble natural bitter compounds found in green vegetables. Our study examined if allele status of a single nucleotide polymorphism (SNP, rs10246939) in the TAS2R38 gene associated with bitter taste perception in vegetables affects: 1) the frequency of reported vegetable consumption prior to, and 2) the change in frequency of vegetable consumption after six months of either an enhanced or a minimal nutrition counseling intervention within the Heart Healthy Lenoir (HHL) study. SNP status was obtained from HHL participants either through DNA isolated from peripheral blood cells using the Infinium Human Omni Express Exome+ BeadChip (Illumina) and standard imputation methods for missing genotypes. Frequency of vegetable intake and covariates (age, gender, race, income) were available for 491 and 373 participants at baseline and at the six‐month follow‐up, respectively. We found that bitter taste genotype at rs10246939 was not associated with vegetable intake at baseline (p=0.90). After the dietary intervention we found a significant difference in frequency of vegetable intake from baseline to follow‐up between groups defined by SNP status (p<0.001); participants that were heterozygous or homozygous for the bitter taste genotype in rs10246939 consumed fewer vegetables suggesting that dietary intervention success regarding dark green vegetable intake may be influenced by underlying genetic differences in taste perceptions. We completed imputation of all three bitter taste receptor gene clusters (chromosomes 5, 7, and 12) within our dietary intervention cohort as well as a plasma carotenoid panel and are currently performing additional association analyses between these additional bitter taste receptor polymorphisms, carotenoid levels, and reported vegetable intake. Our results suggest that bitter taste genetic variation could be utilized in designing interventions to promote healthy eating.

Support or Funding Information

1P50HL105184‐01 National Heart, Lung, and Blood Institute
Validation of Fatty Acids Regulated Genes in Adipocytes and Muscle Cells
Authors: Li Yi , Gonzalez Trevor , Wang Mengyuan , Cheng Elliott
Published: November 2023

The prevalence of obesity/type 2 diabetes has dramatically increased during last two decades in the United States. Environmental factors including diets may play an important role in developing of these conditions. Adipose and muscle tissues are both significantly affected with these diseases. In order to study epigenetic modifications induced by environmental factors, we have been validating genes screened out from adipocytes and muscle cells by microarrays. In this study, 3T3‐L1 adipocytes and L6 muscle cells were cultured in media containing saturated fatty acids to mimic hyperlipidemia conditions, which occur during the development of obesity and type 2 diabetes. DNA microarrays were used to identify differentially expressed genes in adipocytes and muscle cells by saturated and poly unsaturated fatty acids. We have validated some of the genes that were screened out by DNA microarrays including RASA2, MEF2C, GRP78, etc by real time PCR. RASA2 functions as a suppressor of Ras. It may be involved in growth suppression of muscle cells by saturated fatty acids. In addition, it has been confirmed by using Western Blots that saturated fatty acid palmitic acid induces stress in muscle cells and unsaturated fatty acid linoleic acid does not induce cell death through apoptosis pathway. We will further look into if epigenetic mechanisms are involved in regulation of the validated genes.

Support or Funding Information

Startup funds from Texas A&M University‐Kingsville
Variation in ALDH4A1, Proline Intake and Plasma Proteins in a Population of Young Adults
Authors: Jamnik Joseph , Kim Mun Heui , Borchers Christoph , El‐Sohemy Ahmed
Published: November 2023

Background

The effects of dietary proline content on the lifespan of Caenorhabditis elegans have recently been shown to differ between wild‐type strains and those with a mutation in alh‐6, a gene involved in proline metabolism. However, this association has not been examined in humans.

Objective

The objective was to determine whether there is an interaction between dietary proline intake and common genetic variations in the ALDH4A1 gene, the human ortholog of alh‐6, on proteomic biomarkers in humans.

Methods

Subjects were Caucasian participants of the Toronto Nutrigenomics and Health Study (n=488), a cross sectional examination of young adults aged 20–29 years. Dietary proline intake was estimated using a 196‐item semi‐quantitative food frequency questionnaire. A panel of 54 plasma proteins that become dys regulated during the progression of many chronic conditions were measured using a multiple reaction monitoring HPLC‐MS/MS assay. Two single nucleotide polymorphisms (SNPs) in the ALDH4A1 gene (rs9117 and rs4912075) were genotyped and the association between these SNPs and the plasma proteome was examined using general linear models (GLMs) adjusted for age, sex, BMI and hormonal contraceptive use among women. GLMs were then used to determine whether stratification by the median value of energy‐adjusted proline intake modified any observed associations.

Results

There was a significant interaction (p<0.05) between ALDH4A1 variant rs4917025 and proline intake on circulating levels of apolipoprotein I and histidine‐rich glycoprotein, as well as an interaction between rs9117 and proline intake on concentrations of apolipoprotein D, zinc‐α2‐glycoprotein and serum amyloid P‐component (p<0.05).

Conclusion

These results indicate that genetic variation in ALDH4A1 may interact with dietary proline intake in humans to influence concentrations of various proteomics biomarkers of health.

Support or Funding Information

Research support from the Advanced Foods and Materials Network.
Untargeted Profiling of the Urinary Metabolomes of Smokers and Nonsmokers after a Strawberry Intervention
Authors: Teegarden Matthew D , Cichon Morgan J. , Cooperstone Jessica L. , Ahn‐Jarvis Jennifer H. , Weghorst Christopher M , Vodovotz Yael , Schwartz Steven J.
Published: November 2023

A growing body of evidence suggests that a diet rich in fruits and vegetables may reduce the risk of several tobacco‐related cancers. This effect is possibly mediated by the rich profile of phytochemicals found in these products. Promising evidence from laboratory and clinical trials with berries suggest that these fruits and their associated phytochemicals may modulate several risk factors for oral and esophageal cancers. However limited research exists on the metabolic interaction of berry consumption and tobacco exposure. The objective of this work was to investigate changes in the urinary metabolomes of smokers and non‐smokers following a dietary intervention with confections made with whole strawberries. Samples were obtained from a previously conducted placebo‐controlled, randomized, crossover clinical trial, in which smokers and nonsmokers consumed confections containing lyophilized strawberry powder (24 g powder/day) and placebo confections, each for seven days. An untargeted UHPLC‐QTOF‐MS based metabolomic approach was used to profile metabolites present in urine collected during the last 24 hours of each intervention phase. Following multivariate statistical analyses of the over 3000 metabolites detected, metabolic profiles of subjects differentiated primarily by smoking status but also by strawberry or placebo confection consumption. Key distinguishing features included nicotine‐derived metabolites as well as compounds tentatively associated with metabolism of strawberry phytochemicals. These results will inform future work on the prevention of smoking‐related cancers with dietary interventions such as berries.

Support or Funding Information

Clinical trial was supported through the Oho Agricultural Research and Development Center.
Effects of Maternal Vitamin D Deficiency on Fetal Epigenetic Reprogramming
Authors: Xue Jing , Ideraabdullah Folami Y
Published: November 2023

Maternal nutrition plays a prominent role in fetal development and contributes to susceptibility to diseases in offspring throughout their life. One of the ways maternal nutrition may influence fetal development is through epigenetic reprogramming. Evidence shows a direct regulatory role of vitamin D on epigenetic events. We hypothesize that maternal vitamin D deficiency affects fetal epigenetic reprogramming. To test the hypothesis and to characterize the influence of genetic background and parent of origin, we used reciprocal mating pairs of collaborative cross (CC) inbred mouse lines for their advantages in genetic and phenotypic diversity. G0 dams were subject to a modified AIN‐93G diet without vitamin D (low vitamin D diet, LVD) or control AIN‐93G diet 5 wks before mating until 3 wks postpartum. A subset of G1 males were mated to FVB females to generate G2 offspring. Maternal LVD caused contrasting changes in body weight, and increased testis size in adult G1 males. Hormone levels (FSH, LH and testosterone) do not fully explain changes in physical and reproductive parameters. G2 neonates of both genders inherited the contrasting body weight changes observed in G1. To determine the effects of maternal diet on epigenetic reprogramming, we focused on imprinted regions because these regions are more protected during fetal reprogramming and are heavily involved in fetal development. Pyrosequencing was performed on two paternally methylated imprinted control regions (ICRs) (Igf2‐H19 and Dlk1‐Gtl2) and two maternally methylated ICRs (Snrpn and Grb10). We propose that perturbed paternally methylated ICRs in G1 males lead to hypomethylation of the same region in G2, and vice versa for maternally methylated ICRs. Results show expected direction of changes in Igf2‐H19 and Grb10 locus. Altered DNA methylation percentage did not cause statistically significant diet‐induced changes in total mRNA levels as quantified by real‐time PCR. We further measured mRNA levels of DNA methyl‐transferases Dnmt3a, Dnmt3b and Dnmt1, and histone demethylases Kdm3a and Kdm4b in G2 liver. G2 expression of Dnmt3b was significantly upregulated in LVD group in one cross while Dnmt1 downregulated in the reciprocal cross. Evidence to this date indicates a promising role of maternal vitamin D availability on offspring epigenetic reprogramming, with a pronounced parent‐of‐origin interplay. Genome‐wide methyl‐seq is in progress to further characterize germline and soma epigenome changes in response to in utero vitamin D deficiency.
Spontaneous Preterm Delivery, Dietary Choline Intake and DNA Hypomethylation of Tumor Related Genes in Pregnant Women
Authors: Chen Xinhua , Bai Guang , Scholl Theresa O.
Published: November 2023

Aims

Preterm delivery and sub‐optimal fetal growth are associated with each other and affect both mother and infant. Our aims were to determine (1) whether changes in maternal DNA methylation from entry are associated with spontaneous preterm delivery with and without reduced fetal growth and (2) whether dietary nutrient intake including choline and folate are different between preterm cases and term controls.

Methods

We conducted a case‐control study nested within a large prospective cohort (Camden Study). Gene specific methylation was measured by Methyl‐Profiler PCR Array in a Human Breast Cancer Signature Panel of 24 genes from maternal peripheral leukocytes genomic DNA at entry to care and the 3rd trimester (sampled at 16 and 30 weeks of gestation, respectively). Clonal bisulfite DNA sequencing was performed to confirm the changes in selected genes (CYP1B1, GADD45A and CXCL12). A 24‐hour recall of the previous day's diet was obtained at entry (<20 weeks) and weeks 20 and 28 gestation. The total daily intake of nutrients from all three 24‐hour recalls was averaged for the pregnancy. Multivariable ANOVA with control for confounding was used for data analysis.

Results

There was significantly increased DNA unmethylation in 15 of 24 genes during the 3rd trimester in cases of spontaneous preterm delivery (n=23) as compared to the controls (n=19) (p<0.05 ‐ p<0.01 for each gene). Similar results were observed by bisulfite sequencing for 3 genes. The change in DNA methylation between late and early gestation was significantly different in cases (overall increase in unmethylation was 4.5 ± 1.4%) compared to the controls (overall decrease in unmethylation was −13.6 ± 2.8%, p<0.0001). A graded pattern of DNA unmethylation was observed in 15 genes. Cases who delivered preterm with reduced fetal growth had the highest level of unmethylation, cases delivering preterm without reduced fetal growth were next and term controls were lowest in unmethylation (p for trend <0.05 to p<0.01 for each gene). Cases of preterm delivery had significantly lower dietary free (p<0.05) and total choline intake (p<0.01) as well as a trend toward lower folate intake (p>0.05). There were no differences in the intake of macronutrients or other B vitamins.

Conclusions

These data are potentially significant for the identification of women at risk of preterm delivery as well as for the identification of modifiable factors like diet that modulate or influence epigenetic regulation.

Support or Funding Information

NIH ‐ National Institute of Minority and Health Disparities (1R01MD007828 to XC) and University of Medicine and Dentistry of New Jersey Foundation Grant (PC75‐12 to XC).
Long chain Fatty Acid Receptor 4 (FFAR4) mediates EPA‐miR30b axis activation for promoting brown adipogenesis
Authors: Kim Jiyoung , Okla Meshail , Natarajan Sathish Kumar , Chung Soonkyu
Published: November 2023

Emerging evidence suggests that n‐3 poly unsaturated fatty acids (PUFA) promote BAT thermogenesis. However, underlying mechanisms remain elusive. It is well established that free fatty acid receptor 4 (FFAR4) is the n‐3 PUFA receptor, and microRNAs (miR) play a key role for brown adipogenesis. However, regulation of miR by n‐3 PUFA is unknown. Here we hypothesized that activation of FFAR4 by n‐3 PUFA promote brown adipogenesis by modulating miR. To test this hypothesis, brown adipocyte precursor cells were induced to differentiate in the presence and absence of eicosapentaenoic acid (EPA) and investigated the changes of miR during brown adipogenesis. The increase of brown signature genes (e.g., Ucp1, Cidea) by EPA was positively correlated with miR‐30b. Given that miR‐30b increases brown adipogenesis by targeting RIP140, a nuclear receptor corepressor, we further hypothesized that FFAR4 mediates EPA to miR‐30b for brown adipogenesis. Treatment of GW9805, a FFAR4 agonist, recapitulated the increase of brown adipogenic marker Ucp1, Cidea and miR‐30b expression, and the decrease of RIP140. The increase of Ucp1 expression by EPA was dampened by silencing of FFAR4, but augmented by exogenous miR‐30b mimics. Intriguingly, miR‐30b mimic alone was not sufficient to stimulate Ucp1 expression in FFAR4‐silenced cells, suggesting that a signaling interaction between FFAR4 and miR‐30b. Consistently, the blockage of miR‐30b expression by LNA inhibitor remarkably attenuated GW9805‐induced Ucp1 expression. Taken together, our results demonstrate that activation of FFAR4 by n‐3 PUFA increases miR‐30b expression, which further promotes transcriptional activation of brown adipogenesis by targeting transcriptional repressor RIP140.

Support or Funding Information

Supported by NIH 1P20GM104320
A nano‐emulsion of lutein is more effective than regular lutein in reducing cholesterol‐induced liver injury in guinea pigs
Authors: Murillo Ana Gabriela , Norris Gregory H , DiMarco Diana M , Hu Siqi , Luo Yangchao , Blesso Christofer N , Fernandez Maria‐Luz
Published: November 2023

We developed a nano‐emulsion of lutein disolved in medium chain triglyceride (MCT) oil with d‐alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) as the surfactant. The average particle size was 223.6 nm, with a polidispersity index (PDI) of 0.5 and a zeta (ζ) potential of −17 mV. Then the efficacy of this nano emulsion was compared to regular lutein in preventing cholesterol induced liver injury in guinea pigs. Twenty‐four animals fed a hypercholesterolemic diet (0.025% cholesterol) were randomly assigned to either one of three groups: control, lutein (3mg/day of regular lutein) or nano (3mg/day lutein as nano‐emulsion). After 6 weeks the guinea pigs were sacrificed and their tissues were collected for analyses. As we hypothesized there was significantly more lutein in the tissues and plasma of the animals receiving the nano‐emulsion when compared to the other treatments (liver p< 0.001, plasma p< 0.001, adipose (P< 0.001) and eyes (p< 0.001) indicating a greater bioavailability of this carotenoid when a nano‐delivery system is used. In terms of liver health, the nano group showed reduced hepatic steatosis scores (P<0.05) and reduced hepatic total and esterified cholesterol accumulation (P<0.05). Alanine amino transferase (ALT), a marker for liver damage was also reduced in the nano group (P<0.05). Oxidized LDL in plasma, a marker of oxidative stress and atherosclerosis risk, was lower in the nano group (2.8±1.0) when compared to the control group (7.9±2.1) (P<0.05) and hepatic OxLDL was lower in both lutein and nano groups when compared to controls: 9.2 ± 4.3 ng/mL, 12.3 ± 4.3 ng/mL and 21.7 ± 14.4 ng/mL, respectively (P<0.05). Results indicate that giving lutein as a nano‐formulation increases this compound's bioavailability and this higher lutein concentration provides greater protection against cholesterol‐induced hepatic steatosis and oxidative stress than regular lutein.
Serum carotenoids, retinol, and retinyl esters in Midwestern premenopausal women
Authors: Mondloch Stephanie J , Binkley Neil , Arscott Sara , Tanumihardjo Sherry
Published: November 2023

Background

Vitamin A status assessment is not straightforward. Serum carotenoids are reflective of dietary intake of fruits and vegetables and thus, may be helpful in identifying populations with sufficient provitamin A carotenoid intake. These measurements may help support other biomarkers of vitamin A status.

Objectives

This study measured serum carotenoids, retinol, and retinyl esters in 37–50‐year‐old women (n=118) screened for a recent clinical trial.

Methods

Serum carotenoids, retinol, and retinyl esters were determined with ultra‐performance LC. Dietary intakes were determined by Harvard Food Frequency Questionnaire (n=118). Total and regional body fat percentages were determined by DXA (n=63). C‐reactive protein (EIA kit, Cayman Chemical Co., Ann Arbor, MI) was used as a measure of inflammation

Results

Mean total serum carotenoids (α‐ and β‐carotene, β‐cryptoxanthin, lutein, and lycopene) were 2.02 ± 0.76 μmol/L. When lycopene was not included, this value dropped to 1.42 ± 0.70 μmol/L. Provitamin A carotenoids were 1.03 ± 0.62 μmol/L. Serum retinol concentration was 1.55 ± 0.33 μmol/L, and five women had values ≤1.0 μmol/L. Retinyl esters were detected in 36% of subjects (n=43), with an average of 0.05 μmol retinyl esters/L. Retinyl ester percentage of total retinol ranged from 0–29%.

Conclusions

Serum retinol concentration was low in 4.2% of the women. Vitamin A assessment may be enhanced by concurrently determining provitamin A carotenoid profiles and retinyl ester concentrations.

Support or Funding Information

Support: Funded by Standard Process, Inc., an endowment entitled “Friday Chair for Vegetable Processing Research”, and Global Health funds.
Acceptability of Iron‐Biofortified Pearl Millet Among Young Children in Urban Slums of Mumbai, India
Authors: Huey Samantha Lee , Udipi Shobha , Finkelstein Julia L. , Ghugre Padmini , Haas Jere , Thakker Varsha , Thorat Aparna , Salvi Ashwini , Kurpad Anura , Mehta Saurabh
Published: November 2023

Objective

To examine the acceptability of iron‐biofortified (82 ppm Fe) pearl millet (FePM; ICTP 8203) compared to commercially available (28 ppm Fe) pearl millet (CPM) among young children living in urban slums of Mumbai, India, in preparation for an efficacy trial of the biofortified crop.

Methods

Eighteen standardized traditional feeding program recipes were prepared with either FePM or CPM staple cereal flour. Children (n=59; 6–24 months) were recruited from an urban slum in Mumbai to participate in the acceptability study over a one to three day period. The weight (g) of each food product was recorded before and after consumption. T‐tests were used to compare mean intakes of each food product developed for both types of pearl millet.

Results

The consumption and acceptability of food products made with FePM and CPM flour were high in this population. There were no significant differences in consumption of foods developed from ICTP 8203‐Fe PM (mean ± SD = 22.6 ± 9.7 g), compared to the commercially available pearl millet (mean ± SD = 21.9 ± 6.4 g) across all 18 different recipes.

Conclusions

Considering the high acceptability and consumption of food products containing pearl millet and the similarity in the acceptance of recipes with either variety of pearl millet, we conclude that these varieties of pearl millet can be used in a proposed randomized, controlled feeding trial to test the efficacy of FePM for improving iron status, immune function, cognition, and growth in this population.

Support or Funding Information

Harvest Plus
Prepregnancy Vitamin D Deficiency and Placental Growth and Development in Mice
Authors: Gernand Alison D , Cantorna Margherita T , Diaz Francisco J , Snyder Lyndsay M , Hester James M , Vasudevan Sreelakshmi , Kamat Manasi M , Ott Troy L
Published: November 2023

The global prevalence of vitamin D deficiency in women of reproductive age is high. Vitamin D deficiency is linked to numerous adverse pregnancy outcomes with placental origins, including preeclampsia and fetal growth restriction. Our objective was to examine the effect of prepregnancy and early pregnancy vitamin D deficiency on placental growth and vascular development. We modeled vitamin D deficiency using a Cyp27B1 genetic knockout (KO) mouse fed no dietary vitamin D (n=6); these mice cannot convert the circulating vitamin D metabolite to the biologically active metabolite. Wild‐type (WT) mice with a vitamin D sufficient diet were the control (n=6). All mice were fed the respective diet from 3 weeks of age onward. At 8 weeks of age, mice were mated to genetically dissimilar males to produce allogeneic embryos. Mice were euthanized at 12.5 days gestation and placental and fetal morphometry was measured which included fetal and placental weights and the area of the middle cross‐section of the placenta. Placental mRNA was estimated by qPCR for angiogenic proteins (angiopoeitin‐1 (Ang‐1), Ang‐2, vascular endothelial growth factor a (VEGFa), VEGF receptor 1 (VEGFR1), and placental growth factor (PlGF)). Linear regression models were fit with a generalized estimating equation (GEE) for each outcome examined to account for the clustering of placentas/fetuses within mothers. An interaction by fetal sex was also examined for each outcome. KO mice and WT mice had a similar number viable fetuses and a similar percentage of male fetuses at 12.5 days (7.0 vs. 8.3 per mother and 50% vs. 36%, respectively; both p>0.05). There were no statistically significant differences for KO vs. WT offspring for fetal weight or crown‐rump length (p>0.05). There were also no observed differences for placental weight between groups (p>0.05). However, the total area of the cross‐section of the placenta and the fetal area of the placenta were each larger for KO vs. WT mice (1.04 mm, p=0.024, and 0.600 mm, p=0.046, respectively). There were no statistically significant differences for KO vs. WT in placental Ang‐1, Ang‐2, or VEGFR‐1 mRNA (all p>0.05) but, KO placentas exhibited higher expression of PlGF (p=0.015). Further, placentas from KO mothers exhibited lower expression of VEGFa compared to WT placentas and this effect was stronger in placentas of female offspring (p=0.055 for interaction). Prepregnancy and early pregnancy maternal vitamin D deficiency in mice caused differential expression of angiogenic factors and growth of the placenta. These factors should further be studied in human pregnancies.

Support or Funding Information

Penn State College of Health and Human Development
Dietary Protein Bioavailability in Bariatric Surgery Rat Models
Authors: Bruneau Ouafa , Cavin Jean‐Baptiste , Ribeiro‐Parenti Lara , Khodorova Nadezda , Tomé Daniel , Bado André , Le Gall Maude , Gaudichon Claire
Published: November 2023

Introduction

Bariatric surgery is an efficient treatment of massive obesity but can trigger nutritional deficiencies, especially regarding vitamins and proteins. Protein wasting may be observed, but with large variations of prevalence. Additionally to an insufficient protein intake, protein malabsorption logically appears as a risk factor. However, there is little data on protein digestion after bariatric surgery. This study aimed to clarify the risk of protein malabsorption in two rat models of bariatric surgery, sleeve gastrectomy (SG) and Roux‐en‐Y gastric by‐pass (RYGB).

Methods

Rats were fed a high fat diet for 3 months. They underwent RYGB (n=9) or SG (n=7) surgeries. Each group was paired with a sham pair‐fed group (n=4/group). During 15 d post‐surgery, dietary intake, weight and body composition were measured. At day 15 post‐surgery, rats were given a test meal containing 15N labeled proteins and sacrificed 6 h after the meal. Non‐absorbed 15N labeled dietary protein was quantified 6 h after the test meal in gastrointestinal segments (stomach, duodenum, jejunum, ileum, caecum and colon) by elemental analyzer coupled to isotope ratio mass spectrometer. Small intestine morphology was studied by histology.

Results

3/9 rats and 7/7 rats survived to RYGB and SG, respectively. On d 15 post‐surgery, dietary intake was 49 % and 36 % decreased in RYGB and SG groups (P<0.001), respectively. Fat mass decreased by 32 % in both RYGB and SG groups and 21 % in sham pair‐fed groups (P=0.07). Lean mass loss ranged between 10 % in RYGB to 4 % in sham pair‐fed groups without any significant difference between groups. Hypoalbuminemia was observed in all groups. Non‐absorbed dietary nitrogen was similar between groups in small intestinal segments whereas it was higher in colon in RYGB compared to SG rats (2.8 ± 0.3 vs 1.1 ± 0.2 %, P=0.01). True protein digestibility was 93 ± 1.3 %, without any difference between groups. Histology revealed a hypertrophy of the jejunum mucosa after RYGB and SG and ileum mucosa after RYGB.

Conclusion

This study did not show protein malabsorption after RYGB compared to SG or sham operated rats. Jejunum hypertrophy may have compensated the reduction of absorption area and preserved protein bioavailability. Further studies are needed to confirm this result.
Disruption of Mitochondrial Folate Transporter Gene (Slc25A32) Induces Embryonic Lethality and Neural Tube Defects in Mice
Authors: Kim Jimi
Published: November 2023

Neural tube defects (NTDs) are among the most common birth defects in humans. The causes of NTDs are thought to be multifactorial, including genetic, environmental, and nutritional factors. Multiple studies have shown that periconceptional supplementation with folic acid can reduce the incidence of NTDs. Despite more than 40 years of intensive effort, we still do not understand the mechanisms that underlie these folate‐dependent processes. Having a long‐standing interest in transport systems involved in one carbon metabolism, we developed a new mouse NTD model by knocking out the mitochondrial folate transporter MFT (Slc25A32) gene. MFT is an inner mitochondrial membrane protein that transports folates into mitochondria. In the inner mitochondrial membrane, MFT mediates the reversible transport of tetrahydrofolate (THF) between the cytosol and the mitochondrial matrix and plays a role in maintaining folate concentration within the cell.

To examine the function of MFT during embryonic development, embryos had been dissected from heterozygous pregnant MFT+/− dams between E10.5‐E12.5. We analyzed the phenotypes of MFT knockout embryos from heterozygous MFT+/− breeding pairs. All nullizygous MFT−/−embryos exhibited 100% penetrant neural tube defects that were confined mostly to the head region and sometimes extending to the cervical or thoracic region. We determined that loss of a specific folate‐dependent transport protein leads to NTDs and this new mouse model provides insight to understand a folate‐specific transport mechanism of the MFT that underlie folate dependent process of NTD.

Support or Funding Information

Supported in part by National Institutes of Health (NIH) grants HD067244, ES021006, and NS076465 to RHF.
Time‐restricted feeding of a high‐fat diet reduces adiposity and inflammatory cytokine production in mice
Authors: Sundaram Sneha , Yan Lin
Published: November 2023

Disruption of the circadian rhythms contributes to obesity. Restricting feeding to particular times of the day may reset the circadian rhythms and reduce obesity and resulting complications. The present study investigated the effects of time‐restricted feeding (TRF) of a high‐fat diet on adiposity in male C57BL/6 mice. Three‐week‐old mice were fed a low‐fat or high‐fat diet (16% or 45% of energy from corn oil) ad lib or the high‐fat diet restricted to 8 or 12 hours per day during the dark cycle for 11 weeks. Caloric intake of TRF 12‐hour group was similar to, while that of TRF 8‐hour group was slightly but significantly lower than, that of the high‐fat ad lib group. Restricted feeding of the high‐fat diet significantly reduced body fat mass and body weight compared to mice fed the high‐fat diet ad lib. Metabolic analyses showed that there were no significant differences in respiratory exchange ratio (RER) among TRF and high‐fat ad lib groups, but the RER of these groups were significantly lower than the low‐fat group. Energy expenditure of the TRF 8‐hour group, but not the TRF 12‐hour group, was significantly lower than that of the high‐fat ad lib group. Plasma concentrations of ghrelin (a “hunger hormone” that regulates appetite and distribution and use of energy) were significantly increased in TRF groups compared to both low‐fat and high‐fat ad lib groups. Plasma concentrations of insulin, leptin, monocyte chemotactic protein‐1 and tissue inhibitor metalloproteinase‐1 were significantly elevated in the high fat ad lib group and reduced in both TRF groups to the levels of mice fed the low‐fat diet. Taken together, our results showed that consumption of a high‐fat diet led to increases in adiposity and that TRF reduced such an obesogenic process and its associated inflammatory cytokine and angiogenic factor production. Time‐restricted feeding may be a promising strategy in preventing obesity.
The effects of glutamine‐ and n‐3 polyunsaturated fatty acids‐supplemented resuscitation fluid on circulating cytokines and neutrophil activity in rats with trauma‐hemorrhagic shock
Authors: Wu Yi‐Chen , Lo Hui‐Chen , Huang Fu‐Huan
Published: November 2023

Hemorrhagic shock is an emergent condition usually caused by trauma, surgery, and parturition. Patients with hemorrhagic shock suffer from decreased energy and oxygen delivery and need immediate fluid resuscitation. However, extensive volume of resuscitation fluids may increase oxidative stress and activate inflammatory response. Studies showed that n‐3 polyunsaturated fatty acids (PUFAs) have anti‐inflammatory activity and glutamine is the main source of energy for immune cells. Therefore, the aim of the present study was to investigate the effects of n‐3 PUFA‐ and/or glutamine‐supplemented resuscitation fluids on systemic inflammation in rats with trauma‐hemorrhagic shock (THS). Male SD rats suffered with 5 cm laparotomy and catheterization in the left carotid artery and right jugular vein were divided into a sham‐operated group (SM group) and 5 THS groups. For the 5 THS groups, the blood was withdrawn from the left carotid artery to reach a mean arterial pressure 30 to 35 mmHg within 10 min for the induction of THS. After 60 minutes of hypovolemia, THS rats were resuscitated with shed blood and 3‐fold (LR group) or equal volume of lactate Ringer's solutions without (TH group) or with supplementation of L‐alanyl‐L‐glutamine (GN group), n‐3 PUFAs (FA group), or glutamine plus n‐3 PUFAs (GF group) within 10 minutes via right jugular vein. The SM, TH, GN, FA, and GF groups were further infused with continuous, low rate (~1.4 ml/h) of resuscitation fluids for 42 hours. Normal control rats with no surgery (NC group) were also included. The results showed that the TH group had significantly decreased circulating red blood cells, hemoglobin, hematocrit, serum albumin, and plasma myeloperoxidase (MPO) activity, a neutrophil produced enzyme, compared to the NC and SM groups. Compared to the SM group, the LR and TH groups had significantly increased plasma interleukin (IL)‐6 and relative liver weights, respectively. Serum blood urea nitrogen was significantly increased in the LR and TH groups and was further increased in the GN and GF groups. Compared to the TH group, the GN group had significantly increased serum glucose and decreased plasma interferon‐gamma; the FA group had significantly increased spleen weights and plasma MPO activity and decreased plasma interferon‐gamma; and the GF group had significantly decreased plasma IL‐4, IL‐6, tumor‐necrosis factor‐alpha, and interferon‐gamma. These results suggest that n‐3 PUFAs‐supplemented resuscitation fluids with or without glutamine may decrease circulating pro‐and anti‐inflammatory cytokines and increase systemic neutrophil activity in rats with THS.

Support or Funding Information

NSC 102‐2320‐B‐030‐005‐MY3
Effects of Choline Deficiency on Composition of Sow's Milk
Authors: Mudd Austin T , Johnson Stacey K , Alexander Lindsey S , Getty Caitlyn M , Dilger Ryan N
Published: November 2023

Choline is an essential micronutrient required for many biological functions including synthesis of phospholipids, proper neurodevelopment, and DNA methylation. Whereas choline is known to be expressed at high concentrations in early postpartum milk, little emphasis has been placed on how choline status affects maternal milk composition throughout lactation. As such, the objective of this study was to use the choline‐deficient sow model to assess the compositional changes of expressed milk throughout lactation and its impact on piglet growth. Up to 250 ml of milk was collected from 14 sows (n = 7 each on choline‐deficiency and choline‐adequate lactation diets) at each of 3 time‐points from farrowing to weaning: d 0 (colostrum), d 7–9 (mature milk), and d 17–19 (weaning). Colostrum was collected within 6 h of farrowing and 3‐day intervals were used for mature and weaning milk to ensure adequate and representative milk collection. To promote milk letdown, intramuscular injections of oxytocin were administered. Sow milk production and piglet growth were measured using the weigh‐suckle‐weigh procedure on piglet d of age 1, 8, and 18. Piglet bodyweight growth, measured at 2, 7, and 18 d of age, exhibited a main effect of day (P < 0.05); however no interaction (i.e., diet x day) or main effect of diet were observed. Proximate analysis of milk revealed a main effect of day (P < 0.05) for each of the following measures: dry matter, ash, crude protein, organic matter, gross energy, acid‐hydrolyzed fat, lactose, phosphorus, and calcium. Total free choline exhibited a main effect of day (P < 0.05) with choline concentrations decreasing from colostrum to mature and finally weaning milk; no interaction (i.e., diet x day) or main effect of diet were observed. Diet by day interactions were observed for phosphoethanolamine (P = 0.02), threonine (P = 0.01), asparagine (P = 0.04), and cystathionine/allocystathionine (P = 0.01). A main effect of diet was also observed for alpha‐amino‐n‐butyric acid (P = 0.04). In summary, perinatal choline status appears to affect nutrient composition of sow's milk, but these effects were not sufficient to cause differences in piglet growth during the pre‐weaning period.

Support or Funding Information

Support for this project provided by Mead Johnson Nutrition.
Newborn cardiac structural alterations in response to salt restriction or overload during pregnancy
Authors: Seravalli Priscila , Zago Breno Calazans , de Oliveira Ivone Braga , Veras Mariana Matera , Heimann Joel
Published: November 2023

Objective

This study aims to evaluate a possible influence of high‐ or low‐salt diet during pregnancy on heart structure in neonate males and females of Wistar rats.

Methods

Pregnant rats were fed with normal, high‐ or low‐salt diet (NR, HO and HR groups, respectively) from the first day of pregnancy until delivery. Hearts of the newborns (5–6/group) were collected in the first 24 hours of life. Total heart volume (stereology) and nuclear transversal diameter were evaluated.

Results (mean±SEM

table

Conclusion

Alterations in cardiac structure in male but not in female neonates are induced by high‐salt intake during pregnancy.

Support or Funding Information

This study was funded by FAPESP (2013/00458‐7)

HO
NR
HR
Statistical Analysis

Dams weight (g)

351±23*
377±36
386±42
* P<0.05 vs HR

Litter size (n)

14±0.8
14±0.6
14±0.5
NS

Newborns

Body Weight (g)
Male
6.4±0.09*
6.47±0.07
6.45±0.08
* P<0.05 vs NR e HR

Female
5.1±0.07*
6.1±0.09
6.0±0.08
* P<0.05 vs NR e HR

Heart weight (g)
Male
5.9±0.2
6.3±0.2
6.0±0.2
NS

Female
6.1±0.2
6.2±0.1
5.9±0.2
NS

Heart volume (mm3)
Male
2.6±0.14*
3.1±0.12
3.1 ±0.20
* P<0.05 vs NR

Female
2.4±0.10
3.0±0.36
2.8±0.20
NS

Left ventricle nuclear transversal diameter (μm)
Male
5.9±0.1S
5.7±0J21
6.6±0.15*
* P<0.05 vs NR

Female
5.9±0.23
5.5±0.23
6.1±0.25
NS

Right ventricle nuclear transversal diameter (μm)
Male
5.9±0.18
5.6±0.13
6.4±0.31*
* P<0.05 vs NR

Female
5.7±0.20
5.3±0.17
5.8±0.16
NS