bluuebunny/crossref_metadata_2025 huggingface dataset:
Biotransformation of Polymethoxyflavones by Mouse and Human Colonic Microflora
Authors: Ma Changchu , Zheng Jinkai , Warnick Thomas , Leschine Susan , Xiao Hang
Published: June 2021

Colonic microflora plays important roles in biotransformation of dietary components and their biological activities. Polymethoxyflavones (PMFs), a unique class of flavonoids found in citrus fruits have shown many beneficial bioactivities. We investigated the biotransformation of two representative PMFs i.e. nobiletin (NBT) and 5‐hydroxylnobiletin (5HN) by colonic microflora. NBT, 5HN and their metabolites were isolated from the urine of CD‐1 mice after oral administration of NBT or 5HN for 2 weeks. These isolates were subject to anaerobic fermentation by colonic microflora freshly isolated from CD‐1 mice and human volunteers. HPLC analysis demonstrated that colonic microflora had no effect on NBT or 5HN. However, glucuronide and sulfate conjugates of NBT and 5HN metabolites were largely deconjugated by colonic microflora. Colonic microflora also caused demethylation at certain positions of flavonoid core structures, e.g. 3′ and 4′ positions on B‐ring. Both mouse and human colonic microflora produced similar effects on PMFs. Moreover, our results in cell culture models demonstrated that isolates generated after colonic microflora fermentation showed much stronger anti‐inflammatory and anti‐carcinogenic effects than isolates without fermentation. Overall, we provided the first report on the biotransformation of PMFs by colonic microflora and its potential for enhancing health benefits of PMFs.

Grant Funding Source: AICR, NIH, NAS and USDA
Serum levels of coenzyme Q10, tocopherols, and C‐reactive protein in adolescent girls and premenopausal women
Authors: Chai Weiwen , Novotny Rachel , Cooney Robert V , Maskarinec Gertraud , Franke Adrian A , Le Marchand Loic
Published: June 2021

Objective

Given the importance of anti‐oxidant dietary compounds for chronic disease prevention, we examined the differences in serum levels of Coenzyme Q10 (CoQ10), α‐tocopherol (α‐Toc), γ‐tocopherol (γ‐Toc), and C‐reactive protein (CRP) between adolescent girls and premenopausal women.

Methods

Baseline body mass index (BMI) and serum levels of CoQ10, α‐Toc, γ‐Toc, and CRP from 207 adolescent girls (13 to 19 yr) were compared with those from 183 premenopausal women (34 to 47 yr) by t‐test. Associations of age and BMI with serum biomarkers were assessed using multiple regression.

Results

Adolescent girls had significantly lower mean BMI and serum CoQ10, α‐Toc, γ‐Toc, and CRP levels than premenopausal women (BMI: 22.1 vs. 26.1 kg/m2, P <0.0001; CoQ10: 376 vs. 544 ng/mL, P<0.0001; α‐Toc: 6.9 vs. 13.5 μg/mL, P<0.0001; γ‐Toc: 1.28 vs. 1.69 μg/mL, P<0.0001; CRP: 1.29 vs. 2.13 mg/L, P<0.0001). The differences in CoQ10, α‐Toc, and γ‐Toc remained after adjusting for BMI. CRP and γ‐Toc were significantly and positively associated with BMI in both age groups.

Conclusions

Lower serum CoQ10, α‐Toc, γ‐Toc, and CRP levels observed in the adolescent girls relative to premenopausal women suggest that adolescent girls may have reduced need for circulating antioxidants as a consequence of their lower inflammation status as indicated by the lower CRP values.

This research was supported by Department of Defense Grant BC032028 and National Institutes of Health grants R03CA130061 and S10RR020890.
The Hispanic Dietary Mosaic: Assessing the Diet of Women in Puerto Rico in the Atabey Study
Authors: Schelske‐Santos Michelle , Nazario Cruz María , Rosario Rosado Rosa V. , Mansilla‐Rivera Imar , Hernández Johan , Ramírez Marrero Farah A. , McCann Susan , Freudenheim Jo L.
Published: June 2021

Hispanics represent a variety of cultures with roots in Europe, Africa, the Americas, and the Caribbean. Important differences exist in ancestry, disease patterns, health behaviors, and even in language. Appropriate vocabulary and visual aids are essential for dietary assessment, for defining specific food items and portion sizes. Careful distinctions must be made between foods with the same Spanish name, yet different nutrient composition. Incomplete or misclassified dietary data may mask or severely limit the possibilities of demonstrating true correlations between diet and disease, and understanding health disparities.

Objective

In the Atabey Study, we are developing techniques for obtaining culturally‐specific dietary data for women living in Puerto Rico, in order to assess dietary exposures in relation to risk of breast cancer and other co‐morbidities.

Methods

A booklet of photographs was constructed to define portion sizes for key beverages and foods. Questions were designed to distinguish traditional dietary patterns from more acculturated diets both in childhood and adulthood. The nutrient database includes culturally‐specific recipes.

Conclusion

Development of culturally‐specific dietary assessment tools requires in‐depth understanding of the specific population being studied in order to provide insight into underlying health disparities. Funded in part by DOD CDMRP, BC060131
Nutrient composition of regular and low sodium bacon
Authors: Dai Jiexin , Thompson Leslie
Published: June 2021

The objectives of this study are to determine the nutrient composition of regular bacon and low sodium bacon in the United States for inclusion in the USDA National Nutrient Database for Standard Reference, and the key objective was to compare the nutritional composition of low sodium bacon and regular bacon. Retail locations in 12 states, three in each of four regions, were chosen for regular and low sodium bacon procurement. Concentrations of minerals, carbohydrate, vitamin B, vitamin D, fatty acids and cholesterol were determined for regular bacon samples. Low sodium bacon (LSB) samples had less Na (P < 0.05) than regular bacon (RB) samples. Total fat content ranged from 32.85% in regular microwave bacon to 39.27% in raw low sodium bacon, and did not significantly differ from the total fat content of bacon reported in 2003. Saturated fat, monounsaturated fatty acids and polyunsaturated fatty acids content were not significantly different among cooking methods. Trans fatty acid (FA) content of fully cooked regular bacon was significantly higher than values of other cooking methods. Cholesterol values were all significantly higher than values reported in the nutrient database in 2003. Sodium content ranged from 1783.33 mg/100 g in fully cooked regular bacon to 1178.33 mg/100 g in microwave low sodium bacon, and potassium content ranged from 197.67 mg/100 g in raw regular bacon to 525.00 mg/100 g in pan fried bacon.

Grant Funding Source: USDA
Enzyme‐synthesized highly branched maltodextrins have slow glucogenesis at the mucosal α‐glucosidase level and are slowly digestible in vivo
Authors: Lee Byung‐Hoo , Nichols Buford L. , Hamaker Bruce R.
Published: June 2021

For starch digestion, α‐amylase first hydrolyzes starch to produce α‐limit dextrins, followed by complete hydrolysis to glucose by the mucosal α‐glucosidases in the small intestine. It is known that α‐1,6 linkages in starch are hydrolyzed more slowly than α‐1,4 linkages. Here, to create designed slowly digestible carbohydrates, the structure of waxy corn starch (WCS) was modified using a branching enzyme alone (BE) and an in combination with β‐amylase (BA) to increase further the α‐1,6 branching ratio. Enzyme‐modified products (BE‐WCS and BEBA‐WCS) had increased percentage of α‐1,6 linkages (WCS: 5.3%, BE‐WCS: 7.1%, and BEBA‐WCS: 12.9%). Hydrolysis by human pancreatic α‐amylase resulted in an increase in the amount of branched α‐limit dextrin from 26.8% (WCS) to 56.8% (BEBA‐WCS). The α‐amylolyzed samples were hydrolyzed by the individual α‐glucosidases and glucogenesis decreased as the branching ratio increased. This result showed that hydrolysis rate of the mucosal α‐glucosidases was limited by the amount of branched α‐limit dextrin. When samples were gavaged to rats, the level of postprandial blood glucose at 60 min from BEBA‐WCS was significantly higher than for WCS or BE‐WCS. Thus, highly branched glucan structures modified by BE and BA had a comparably slow digesting property both in vitro and in vivo. Such highly branched α‐glucans show promise as a food ingredient to control postprandial glucose levels.

Grant Funding Source: USDA AFRI competitive grant program
Distinct Role of Rheb and Grb10 in the Regulation of mTORC1 Signaling in Skeletal Muscle of Neonatal Pigs
Authors: Suryawan Agus , Nguyen Hanh V. , Davis Teresa A.
Published: June 2021

Activation of the insulin and mTORC1 signaling pathways leading to protein synthesis is enhanced in skeletal muscle of the newborn. Recent in vitro studies indicate that Rheb and v‐ATPase are crucial for mTORC1 activation and Grb10, a potent insulin signaling inhibitor, is a vital target of mTORC1. Rheb‐induced mTORC1 activation is characterized by interaction of Rheb with mTORC1 and Ragulator, i.e., LAMTOR1 and ROBDL3. This study aimed to determine the effects of the post‐prandial rise in insulin and amino acids on the activation and/or abundance of Rheb, Grb10, LAMTOR1, ROBDL3, and v‐ATPase in muscle and whether the responses are modified by development. Overnight fasted 6‐ and 26‐day‐old pigs were infused for 2 h with saline or with insulin (I) or amino acids (AA) to achieve fed levels. Formation of the RhebmTORC1 complex in muscle was increased by both I and AA and the response was greater in 6‐ than in 26‐day‐old pigs. The abundance of LAMTOR1, ROBDL3 and v‐ATPase was higher and Grb10 was lower in 6‐ than in 26‐day‐old pigs. Neither I nor AA altered the abundance of these components. Both I and AA increased phosphorylation of Grb10 but the response was not affected by age. These results suggest that the enhanced activation of the mTORC1 signaling pathway in neonatal pigs is in part due to regulation by Rheb, LAMTOR1, ROBDL3, v‐ATPase, and Grb10. (Supported by NIH AR444474 and USDA/ARS 6250–51000‐055)
Further studies on the sensory motor integration of gill lateral cilia in the bivalve mollusc Crassostrea virginica
Authors: Williams Patricka , Akande Patrick , Catapane Edward J. , Carroll Margaret A.
Published: June 2021

Lateral gill cilia of Crassostrea virginica are controlled by serotonin‐dopamine innervation. The motor aspects have been well studied, but the sensory side has not. We studied effects of sensory stimulations to mantle on beating of gill cilia of C. virginica. Applying Isochrysis, a food source, to mantle rim increased beating, whereas crab extract reduced it. The responses were abolished by cutting nervous innervation to gill. Stimulating mantle nerves increased beating. Histamine, which does not alter beating when applied to gill, decreased beating when applied to mantle. This was not seen when nervous innervation to gill was transected suggesting histamine maybe a neurotransmitter of mantle receptor cells that synapse with afferents going to the visceral ganglia. The neurotransmitters serotonin, dopamine, acetylcholine, GABA and FMRFamide had no effect on beating when applied to mantle rim. The study shows sensory‐motor integration of beating of lateral cilia involving the sensory mantle rim and visceral and cerebral ganglia. It appears animals sense harmful cues and food, and adjust gill cilia beating appropriately. The results also suggest the sensory apparatus involved are sensory nerves that send axons to the visceral ganglia, and sensory receptor cells that synapse in the mantle rim with afferent neurons. Supported by 2R25GM06003 of NIGMS, 0516041171 of NYSDOE and 0622197 of NSF.
Comparing glycine and serine kinetics in adolescent girls and adult women during early and late pregnancy
Authors: Hsu Jean W , Thame Minerva M , Fletcher Horace M , Baker Tameka M , Tang Grace J , Jahoor Farook
Published: June 2021

During pregnancy, glycine (Gly) and serine (Ser) becomes more important because they are the primary suppliers of methyl groups for synthesis of fetal DNA and Gly is also required for collagen synthesis. The objective of this study was to measure and compare Gly and Ser kinetics of pregnant adolescent girls and adult women in the first (13.0±0.4 wk of gestation) and third trimesters (28.8±0.4 wk of gestation). Measurements were made in the fasted state by continuous intravenous infusions of 2H2‐Gly and 15N‐Ser in 11 adolescent girls (17.4±0.1 y of age) and in 10 adult women (25.8±0.5 y of age) for 6 h.

Adult women
Adolescent girls

Flux
1st trimester
3rd trimester
1st trimester
3rd trimester

μmol/kg/h

Gly
156±14
136±9
165±11
142±7*

Ser
129±15
119±13
133±11
111±6

Gly→Ser
4.2±0.6
4.2±0.5
4.3±0.5
4.8±0.4

Ser→Gly
62±9
57±7
70±7
54±3*

Different vs. trimester 1 value, P<0.05, paired t‐test.

Adolescent girls had significantly slower glycine flux and made less glycine from serine in the 3rd trimester (P < 0.05). Baby's birth length was significantly shorter in adolescent girl (P = 0.04), and baby's birth weight was 7% less compared with mean values of adult women. These findings suggest that pregnant adolescents could not maintain Gly production in late pregnancy compared to early pregnancy, which makes their fetus more vulnerable to impaired cartilage synthesis, hence linear growth. Supported by USDA Grant # 58–6250‐6001
Improved thermoregulatory and autonomic responses contribute to reduced fatigue and faster recovery from exertional heat stress by sympatholytic treatment with clonidine
Authors: Stauss Harald Martin , Choudhary Navita , Moss Ann M , Kregel Kevin C
Published: June 2021

We investigated the effect of clonidine (C, 33 μg/kg/day, osmotic pumps) on thermoregulatory and autonomic responses to chronic exposure to exertional (ExHS) and non‐exertional (HS) heat stress in rats. Blood pressure (BP), heart rate (HR) and core temperature (Tc) were recorded telemetrically before, during, and after a 5‐day (twice a day) ExHS, HS, or sham protocol. During the five protocol days, nocturnal Tc and HR were elevated in placebo‐treated rats (P) exposed to ExHS and HS. C reduced these increases in Tc and HR, suggesting improved thermoregulation. Nocturnal BP in P was more elevated in ExHS than in HS. C reduced nocturnal BP in ExHS, suggesting increased sympathetic tone in P exposed to ExHS. Similarly, in P, low frequency systolic BP variability (LFSYS), reflecting sympathetic modulation of vascular tone, was more elevated in ExHS than in HS and C reduced this elevated LFSYS in ExHS. Likely due to fatigue, exploratory behavior (open field test) declined during the 5 protocol days in ExHS and HS. In ExHS, this effect was blunted by C. Furthermore, recovery of exploratory behavior in ExHS was more pronounced and faster in C‐treated rats compared to P. C improves thermoregulation and reduces sympathetic responses to chronic exposure to ExHS. These effects of C may reduce fatigue and contribute to faster recovery following chronic exposure to ExHS.

Supported by funding from DoD/USAMRMC #W81XWH‐10–2‐0115.
Development of Endothermy in the Pekin Duck (Anas pekin)
Authors: Ream Sarah , Duquaine Allison , Sirsat Sarah K Goy , Sirsat Tushar S , Dzialowski Edward M
Published: June 2021

Maturation of metabolic capacity is associated with attaining endothermy in avian species. Here we examined development of endothermy in precocial Pekin ducks (Anas pekin) by measuring whole animal O2 consumption (Vo2) at 35, 25, and 15°C and ventricle mass, hemoglobin (Hb), and hematocrit (hct) as measures of O2 delivery capacity. Citrate synthase activity and mitochondria respiration of permeabilized skeletal muscle were measured to elucidate associated cellular level changes. Animals were examined at the prehatch externally pipped (EP) stage through 19 hrs post hatching. The Vo2 of EP embryos decreased, but not significantly when cooling from 35 to 25, and 15°C. In hatchlings 0 to 19 hrs post hatching, Vo2 increased significantly during cooling from 35°C to 25 and 15°C. Citrate synthase activity of thigh flexor muscles showed a non‐significant, increasing trend with age. While body mass did not differ between ages, whole ventricle mass increased significantly upon hatching. Both Hb and hct increased significantly from EP to 0 and 12 hrs post hatching. Increased metabolic capacity necessary to attain endothermy was associated with increasing metabolic capacity of the tissue and increasing O2 delivery capacity. This change in capacity was obtained rapidly upon hatching as evident by the increase in ventricle mass and is supported by increases in Hb and hct levels in hatchlings. Supported by NSF IOS 1146758 (EMD).
Chelating agents reverse neurotoxic effects of manganese on dopaminergic innervation of gill of the bivalve mollusc Crassostrea virginica
Authors: Ojo Christiana , Rogers Keisha , Adams Trevon , Catapane Edward J. , Carroll Margaret A.
Published: June 2021

Lateral gill cilia of Crassostrea virginica are controlled by a serotonin‐dopamine (DA) innervation. DA is an inhibitory transmitter at gill causing cilio‐inhibition. Manganese (Mn) is a neurotoxin causing Manganism in people exposed to high levels in air. Clinical interventions for Manganism have not been successful. Recently, p‐aminosalicylic acid (PAS) was reported to provide effective treatment of Manganism. PAS is an anti‐inflammatory drug with chelating properties. We showed treatments of C. virginica with Mn disrupts DA innervation of gill. Pre‐or co‐treatments with PAS or EDTA prevented it. We hypothesized chelating agents would be effective in reversing neurotoxic effects of Mn when applied after Mn. We used gills of C. virginica to measure lateral cilia beating rates of preparations treated first with Mn followed by treatments with either PAS, EDTA or DMSA (meso‐2,3‐dimercaptosuccinic acid). Dose responses of PAS, EDTA and DMSA (10−11–10−4M) against beating were conducted after 100 FM of Mn was added to gill. All 3 drugs reversed the neurotoxic effects of Mn in a dose‐dependent manner. DMSA was the most potent. The study demonstrates these chelators are effective in reversing acute neurtoxicity of Mn. This information should be of interest to those designing therapeutic drug treatments for Manganism. Supported by 2R25GM06003 of NIGMS, 0516041171 of NYSDOE and 0622197 of NSF.
Myocardial gene expression of the tinamou reflects the physiological challenges of having a small heart
Authors: Österman Hanna , Ekström Andreas , Garitano‐Zavala Álvaro , Altimiras Jordi
Published: June 2021

Tinamous are an ancient family of neotropical flying birds that occupy diverse habitats from lowland jungle forests to the Andean high plateaus. Tinamous have a very small heart, closer to that of non‐avian reptiles than to birds with similar living styles. Even though tinamous are endothermic, the small heart size compromises oxygen transport, aerobic metabolism and thermoregulation. This led us to hypothesize that gene expression in the heart of tinamous would reflect the basal scenario from which neognate birds, with larger hearts and higher aerobic capacity, evolved. A microarray analysis was performed to determine differences in gene expression between tinamou and chicken myocardium. Key genes involved in cardiac remodeling and hypertrophy were up regulated in tinamous, including PI3Kα, TGFβII, TAK1, FGF and PDGFRα. This indicates elevated activity in hypertrophic pathways and is consistent with previous indications of left ventricular hypertrophy in N.ornata. Up regulation of key glycolytic enzymes was also observed, namely PFK‐1, FBPase‐2 and ALDOB, indicating an increase in cardiac glycolytic metabolism in N.ornata compared to high altitude chickens. These gene expression differences reflect the physiological challenges of being endothermic while having a small heart. Supported by FORMAS Centre of Excellence in Animal Welfare Science and career grant from Linköpings universitet to JA.
Changes in cerebral scattering and hemodynamics associated with acute mountain sickness
Authors: DiPasquale Dana M. , Li Zhi , Muza Stephen R. , Strangman Gary E.
Published: June 2021

Rapid ascent to high altitude can lead to acute mountain sickness (AMS). A cerebral etiology is hypothesized for AMS, including edema and vascular changes, both of which are theoretically detectable by radio‐frequency near‐infrared spectroscopy. To induce a range of AMS symptoms, 13 subjects were exposed to either 8 h of low altitude (300m), high altitude (4400m) or normobaric hypoxia (PO2=91 mmHg). Baseline tissue scattering (μs’), oxy‐/deoxy‐/total‐hemoglobin concentrations, and AMS symptoms (Environmental Symptoms Questionnaire) were collected during exposure. Resting μs’ at 690, 790, and 830nm was lower at times when subjects had AMS (AMS‐C score ≥0.7; p<0.05), suggesting the presence of cerebral edema when subjects had AMS. Oxy‐, deoxy‐and total‐Hb concentrations were also lower when subjects had AMS (p<0.05). The hemoglobin results suggest reduced cerebral perfusion associated with the development of AMS. We hypothesize these cerebral effects are directly related to the as yet unknown mechanism underlying AMS. Supported by DOD Defense Medical Research and Development Program, award number W81XWH1020199. Authors’ views, not official Army or DoD policy.
Basolateral Amino Acid Transport investigated using MDCK Epithelia and Mouse Models
Authors: Guetg Adriano , Torrente Marta , Mariotta Luca , Camargo Simone M.R. , Verrey François
Published: June 2021

Amino acids (AAs) are (re)absorbed from the small intestine and the kidney proximal tubule epithelia via specific luminal and basolateral AA transporters (AATs). The basolateral exit step of this transcellular transport is less well understood than the luminal uptake. In particular, the cooperative role of the neutral AA antiporter LAT2 (SLC7A8) and that of the two uniporters TAT1 (SLC16A10) and LAT4 (SLC43A2) that transport aromatic AAs and β‐branched AAs respectively needs to be clarified. To investigate this issue we reconstituted the major transepithelial transport machinery for neutral amino acids in Madin‐Darby Canine Kidney (MDCK) cells to test its function. Measurements of intracellular AA showed that the additional expression of TAT1 in cells expressing LAT2 resulted not only in an increase of the basolateral efflux of TAT1 substrates but also of all other LAT2 AA substrates supporting the hypothesis that TAT1 enhances LAT2 function by recycling its exchange substrates. Furthermore, to investigate the role of LAT4 in vivo we determined its protein localization and characterized Lat4 −/− knock‐out (KO) mice. We detected LAT4 in kidney proximal tubule and thick ascending limb epithelial cells as well as in the enterocytes of small intestine villi. Interestingly, Lat4−/− KO mouse has a lethal phenotype pointing to an important physiological role of LAT4. Supported by Swiss NSF grant 31–130471 to FV.
The assumption of heterogeneity in a mathematical model of the parathyroids leads to improved qualitative and quantitative responses to complex stimuli
Authors: Pruett William Andrew , Hester Robert L
Published: June 2021

The dynamics of parathyroid hormone (PTH) secretion in response to calcium perturbation are complex, requiring a solution that passes beyond the four‐parameter steady state solution proposed by Brown. It has been previously noted that dispersed parathyroid cells have disparate responses to hypocalcemia. This suggests that dynamic heterogeneity in the parathyroid cell population plays an important role in the response to calcium perturbation. To implement this assumption in an existing model of PTH secretion incorporating storage and variable receptor expression, we simulated heterogeneous glands by simultaneously sampling model parameters 15 times and averaging the responses. We compared model response to two simple and three complex hypo‐ and hypercalcemic clamping protocols to individual responses reported by Schwarz. Existing (homogeneous) models of PTH secretion were insufficient to predict individual responses in all five curves simultaneously. 1000 heterogeneous glands were simulated, and distribution functions were (numerically) generated from this data. Over 90% of the human data amalgamated between the five experiments lay within the 95% CI for the simulations, demonstrating significant improvement over existing models. In conclusion, introducing heterogeneity increase the physiologic relevance and performance of the PTH model. Supported by NSF EPSCoR and 1T32HL105324.
The effect of substrate stiffness on the apparent stress cells experience during cyclic strain
Authors: Huntsman Heather D. , Ozturk Tuna , Boppart Marni D. , Kemkemer Ralf
Published: June 2021

The mechanical microenvironment of a cell is defined by both substrate stiffness and the external forces applied to it. Combined these variables have been shown to influence cell differentiation, proliferation, and motility. The purpose of this study was to assess the interrelated effects of mechanical stimuli on the apparent stress experienced by human dermal fibroblasts. Due to its high biocompatibility, polydimethylsiloxane (PDMS) was used to develop a 2D in vitro surface with tunable stiffness. Substrate stiffness, as measured by a rotational rheometer, was adjusted from a Young's modulus of 10kPa to 110kPa by adjusting the ratio of curing agent added to the pre‐polymer. The soft gels were directly cast onto a stiffer 6‐well PDMS base, and it was confirmed that strain was directly transmitted through the ~ 200μm thick soft gels. Gels were coated with fibronectin and 8% uniaxial strain was applied using a custom made stretching system. Allowing 24 hours for attachment, cell deformation was measured as the change in cell length parallel to the axis of strain. Comparing the gels, cells seeded on the stiff gels deformed 22% more than those seeded on the soft gels (p < 0.05). These data suggest that the mechanical signal is modified by the underlying substrate stiffness and could have implications for signal mechanotransduction. This research was funded by the National Science Foundation, IGERT‐CMMB.
Sugar‐sweetened beverage consumption is associated with relative distribution of abdominal adipose tissue in the Framingham Heart Study
Authors: Ma Jiantao , Sloan Matthew , Fox Caroline S , Hoffmann Udo , Jacques Paul F , McKeown Nicola M
Published: June 2021

Sugar‐sweetened beverages (SSB), the largest contributor of ‘added sugar’ intake in the US diet, have been associated with increased cardiometabolic risk. Recently, the relative distribution of abdominal fat, i.e. the propensity of fat stored in visceral adipose tissue (VAT) relative to subcutaneous adipose tissue (SAT), has been independently linked with cardiometabolic risk. We examined the cross‐sectional association between SSB intake and VAT‐to‐SAT ratio in a sub‐cohort of the Framingham Heart Study (n=2,389; 49% women; 51 y). VAT and SAT were measured using multi‐detector CT, and SSB intake was estimated using a food frequency questionnaire. Participants were categorized as SSB non‐consumers or consumers (grouped as 1–2 servings/wk, 3–6 servings/wk, and ≥1 servings/d). After adjustment for age, sex, energy intake, smoking, alcohol intake, dietary fiber, total fat, fruit and vegetable intake, SSB was positively associated with VAT‐to‐SAT ratio (0.54 in non‐consumers vs. 0.63 in the highest consumers; P trend <0.0001). Further adjustment for BMI, VAT or SAT did not change the relationship, suggesting this association is independent of absolute fat quantity. There was no significant association between diet soda and VAT‐to‐SAT ratio or %VAT. Our study demonstrates that adults who consume just one daily SSB have a greater propensity to deposit fat viscerally as compared to subcutaneously.

Grant Funding Source: the NIH/NHLBI (Contract N01‐HC‐25195) and the USDA (USDA agreement No. 58–1950‐7–707)
Differential effect of docosahexaenoic acid (DHA) versus myrisitc acid (MA) on inflammatory cytokines
Authors: Honda Kaori LeeAnn , Matthan Nirupa R , Lamon‐Fava Stefania , Wu Dayong , Lichtenstein Alice H
Published: June 2021

DHA has anti‐inflammatory properties, but its ability to downregulate individual pro‐inflammatory cytokines is undefined. We observed in the RAW 264.7 macrophage cell line (RAW) that treatment with DHA but not MA decreased lipopolysaccharide (LPS)‐induced IL‐6 protein and mRNA but not TNFα. We studied the potential mechanisms by which DHA differentially regulated TNFα and IL‐6 expression induced by LPS — modulation of CREB activation (P‐CREB), nuclear translocation of NFKB p50, and prostaglandin (PG)E2 secretion. RAW cells were treated with DHA or MA (100 μM, 24hr) prior to LPS exposure (100 ηg/mL). P‐CREB and PGE2 secretion were measured by ELISA and p50 nuclear translocation by Western Blot. LPS significantly induced PGE2 secretion, and P‐CREB and nuclear p50 levels. p50 inhibition with a synthetic peptide increased TNFα and decreased IL‐6 gene expression, while addition of exogenous PGE2 reduced TNFα but not IL‐6 mRNA. DHA but not MA significantly reduced PGE2 secretion and basal (not LPS‐induced) P‐CREB levels, but unexpectedly, did not alter nuclear p50 levels. These data indicate that both nuclear p50 and PGE2 inhibited LPS‐induced TNFα mRNA, but either increased or did not reduce IL‐6 mRNA. Only PGE2 secretion in RAW cells was modified by DHA, suggesting that the differential effect of DHA on IL‐6 and TNFα expression can be due to decrease in PGE2 secretion which regulates TNFα but not IL‐6 mRNA.

Grant Funding Source: NHLIBI‐T32‐HL069772, USDA 58–1950‐0–0014
Dose‐response effect of marine‐derived omega‐3 fatty acids on erythrocyte membrane fatty acid content: double‐blind randomized controlled trial
Authors: Flock Michael R , Skulas‐Ray Ann C , Harris William S , Fleming Jennifer A , Kris‐Etherton Penny M
Published: June 2021

Erythrocyte membrane content of EPA and DHA, the omega‐3 index (O3I), predicts cardiovascular disease mortality. Dietary intake of EPA+DHA is the main determinant of the O3I, yet the influence of other factors remains unclear. Our objective was to evaluate the dose‐response relationship of supplemental EPA+DHA intake on O3I, and by using a regression‐based approach, to identify predictors of treatment response that modulate the effects of supplementation. We conducted a placebo‐controlled, double blind, parallel study in healthy men and women with low EPA+DHA consumption. Subjects (n=125) were randomized to one of five doses (0, 300, 600, 900, 1,800 mg) of EPA+DHA given daily in fish oil supplements for approximately 5 months. A total of 116 subjects completed the study. There were no significant differences between groups at baseline. The O3I increased in a dose‐dependent manner (p<0.0001), with treatment alone predicting 67% of the variability in the O3I response with a quadratic fit. A multivariate model that included additional significant predictors: BMI, gender, age, and baseline O3I, explained 76.5% of the change in O3I. Thus, our results demonstrate the validity of the O3I as a biomarker of EPA+DHA supplementation and identify additional factors that may be used to tailor individual EPA + DHA recommendations in order to achieve an optimal O3I.

Grant Funding Source: USDA
High fat breakfasts affect antioxidant and oxidative biomarkers more in metabolic syndrome subjects compared with healthy controls
Authors: Lewandowski Paul , van Egmond Gregory , Larsen Amy , Bonham Maxine , McCoombe Scott , Sinclair Andrew , Cameron‐Smith David
Published: June 2021

This study compared the acute postprandial effects on antioxidant and oxidative biomarkers in subjects with or without metabolic syndrome (MetS) after high‐fat dairy or high‐fat vegetable‐based breakfast. 21 male subjects (11 MetS; 10 control) consumed the breakfasts on separate occasions in random order. Fasting (12h) blood was collected at baseline, 1h, 2h, 3h, 4h and 5h post‐meal. The antioxidant measures of red blood cell glutathione (GSH/GSSG), plasma total antioxidant status (TAS), superoxide dismutase (SOD) and catalase (CAT) did not differ significantly between MetS and control subjects following consumption of the dairy‐based breakfast. However consumption of the vegetablebased breakfast by MetS subjects induced a significantly higher state of antioxidant defences, which was demonstrated by higher GSH/GSSG ratio (1h), elevated SOD levels (1h‐5h) and increased CAT activity (2h & 3h) compared with the control subjects. High‐fat breakfasts affected antioxidant and oxidative biomarkers differently in male subjects with MetS compared to healthy controls. These findings are indicative of greater antioxidant fluctuation and higher levels of oxidative biomarkers in MetS subjects compared to healthy controls irrespective of the fat type in the breakfast. The study was supported by the Australian Dairy Health and Nutrition Consortium; GPvE received an Australian Postgraduate Award.
Snacks are not food: low‐income mothers’ definitions and feeding practices around child snacking
Authors: Fisher Jennifer Orlet , Wright Gretchen , Herman Allison , Malhotra Khushi , Serrano Elena L. , Foster Gary D. , Whitaker Robert C.
Published: June 2021

Snacking among US children has increased in recent decades and is a key source of “empty” calories, but is ambiguously defined and poorly understood from a parenting perspective. This qualitative research examined low‐income mothers’ definitions and feeding practices around child snacking. Seven focus groups were conducted with 32 low‐income, African American mothers of preschoolers who were recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children offices in Philadelphia, PA. Three coders analyzed transcripts using a constant comparative method to elucidate major themes. More than half of mothers were obese and reported education beyond high school. Roughly 1/5 reported household food insecurity. Results revealed that mothers did not view snacks as food. Snacks were described as being cold, convenient, and appealing to children, but involving less nourishment and structure than meals. Mothers used snacks to manage their children's behavior and to satisfy their own hedonic eating. Feeding strategies centered on limiting children's access by locking cabinets, offering small individual packages, and limiting the number of snacks in sight. These findings suggest that low‐income mothers view snacks as powerful hedonic tools for child behavior management that involve less planning and lower expectations for nutrition than meals. Supported by USDA 2011–68001‐30148.
Predictors of Sugar‐Sweetened Beverage (SSB) Consumption Classification among Urban Low Income Pre‐School Children
Authors: Glenn David Robert , Lora Karina , Wakefield Dorothy
Published: June 2021

This study determined predictors of child classification SSBs (flavored milk, fluid and powdered juice drinks, iced tea, energy drinks and soda) consumption by using inductive methods to predict behavior. Study included 462 low‐income caregivers of 3–5 y. old children. Two‐third of children consumed SSBs. Independent variables (IV) included demographics, anthropometrics, food security assessment, a feeding practices questionnaire, and an Information‐Motivation‐Behavioral Skills (IMB) –based SSB consumption questionnaire. Using data mining algorithms QUEST, Exhaustive CHAID, and CART to build models, we tested 75 IV and over 500,000 interaction effects. The IMB‐based beverage questionnaire was the source of all three models’ predictive power. Across the three models, the following three questions predicted whether children were classified as consumers versus non‐consumers: lacking the skill to encourage the child to drink water instead of other drinks, thinking that “child is old enough to have juice drinks or drinks that might have some fruit juice in them,” and responding that “as long as a drink has some fruit juice in it, it is healthy.” Models had high predictive accuracy (68.2%) and sensitivity, but specificity was mediocre. In conclusion, SSBs caregivers’ information and behavioral skills influenced their children's consumption of SSBs. Funding: USDA/NRI 2008–55215‐19071.

The study was funded by the USDA

Grant Funding Source: USDA
Zinc supplementation normalizes gene expression and enhances neurogenesis in a rat model of traumatic brain injury
Authors: Cope Elise C. , Levenson Cathy W.
Published: June 2021

New interventions are needed to improve resilience to traumatic brain injury (TBI). To examine the role of zinc, rats were fed a zinc adequate (30 ppm) or supplemented (180 ppm) diet for 4 wks followed by a frontal cortex TBI using controlled cortical impact. Chronic zinc supplementation significantly improved spatial learning and memory, and reduced anxiety and depression‐like behaviors. Mechanistically, we hypothesized that zinc supplementation would prevent injury‐induced changes in gene expression and enhance hippocampal stem cell proliferation and survival. Hippocampal RNA was extracted 48 h after TBI to analyze mRNA abundance via the NimbleGen platform microarray. TBI altered the expression of over 170 mRNAs, approximately 70 of which were normalized in rats supplemented with zinc (p<0.01). We identified genes involved in cell proliferation, apoptosis, survival, repair, and differentiation. Rats were also injected with the thymidine analogue EdU to label proliferating cells in the hippocampus. TBI doubled the number of proliferating cells in the dentate gyrus granular cell layer 24 h post‐injury (p<0.05), and supplemental zinc increased this number by an additional 2 fold (p<0.05). Ongoing work is characterizing the long‐term fate of these cells. These data show that zinc can be a novel and effective strategy for preventing adverse cellular, molecular, and behavioral outcomes associated with TBI.

Grant Funding Source: Department of Defense/US Army MRMC
Choline affects placental vascular function and development in a dose response manner
Authors: Jiang Xinyin , Jones Sara , Ganti Anita , Andrew Benjamin , Brannon Patsy , Roberson Mark , Caudill Marie
Published: June 2021

This study explored the role of choline in placental vascular function. In a 12‐week controlled feeding study among third trimester pregnant women, the higher choline intake group (930 vs. 480 mg/d) had lower (P=0.05) placental and circulating levels of soluble fms‐like tyrosine kinase‐1 (sFLT1), an anti‐angiogenic factor that predicts preeclampsia risk. The effect of choline on placental cell function was further investigated using immortalized HTR‐8/SVneo trophoblasts cultured in different choline concentrations (28, 13 and 8 μM) for 96 hours. The decrease in choline concentrations led to a graded increase (P<0.01) in the gene expression and secretion of sFLT1, expression of the proinflammatory markers [e.g. interleukin 1 beta (IL1B)], apoptosis and oxidative stress. Cellular phosphatidylcholine dramatically decreased (50%, P<0.01) in the lower choline group, whereas the protein kinase C (PKC) isoforms δ and ε, activated by breakdown products of phosphatidylcholine, increased (P<0.01). The addition of a PKC inhibitor partially rescued the increased expression of sFLT1 and apoptosis. In conclusion, choline influences placental vascular function partially via PKC.

Grant Funding Source: USDA NIFA AFRI003397
Identification of colonic metabolites of 5‐hydroxylnobiletin and their roles in colon cancer inhibition
Authors: Zheng Jinkai , Song Mingyue , Charoensinphon Noppawat , Xiao Hang
Published: June 2021

Previously, we reported that oral administration of 5‐ hydroxylnobiletin (5HN, a citrus flavonoid) potently inhibited colon carcinogenesis in mice. To further understand the molecular mechanism involved, we investigated colonic metabolism of 5HN in mice after oral administration for 16 weeks. Utilizing HPLC, UV spectroscopy, 1H and 13C NMR, and mass spectroscopy, we identified 8 metabolites of 5HN in the colon. They are mono‐, di‐, or tri‐demethylated derivatives of 5HN. We synthesized 3 major metabolites i.e. 5,3′‐didemethylnobiletin (M1), 5,4′‐ didemethylnobiletin (M2), and 5,3′,4′‐tridemethylnobiletin (M3), and compared their bioactivities with those of 5HN. All 3 metabolites showed stronger anti‐proliferative and pro‐apoptotic effects on colon cancer cells than 5HN, especially M1 was more than 50‐fold stronger than 5HN. M1 showed similar antiinflammatory effects as 5HN in lipopolysaccharide‐stimulated macrophages, while M2 was 3‐fold more potent in anti‐inflammation than 5HN. Moreover, M1 showed more than 10‐fold stronger anti‐angiogenic activities than 5HN in a capillary tube formation assay of human umbilical vein endothelial cells. In conclusion, our results demonstrated that colonic metabolites of 5HN had potent activities in inhibiting cancer cell growth, suppressing inflammation, and decreasing angiogenesis, which may contribute significantly to colon cancer inhibition.

Grant Funding Source: NIH, AICR and USDA
Vitamin E reverses age‐associated susceptibility to Streptococcus pneumoniae lung infection
Authors: Ghanem Elsa Bou , Du Xiaogang , Wu Dayong , Camilli Andrew , Leong John , Meydani Simin Nikbin
Published: June 2021

Streptococcus pneumoniae (pneumococcus) infections in the elderly create a considerable health and economic burden in the USA. The objective of this study was to test whether vitamin E, a potent immune‐regulator, can be used as a preventive strategy to mitigate the age‐associated decline in resistance to pneumococcus. To test that, young (4‐mo) and old (22‐mo) mice were fed a diet containing 30 PPM (control) or 500 PPM (supplemented) vitamin E for 4 weeks and then intra‐tracheally challenged with the pneumococcal strain TIGR4. Results showed that, on the control diet, old mice were significantly more susceptible to pneumococcal infection than young mice. Remarkably, this age‐related difference was completely reversed by vitamin E supplementation: supplemented old mice had drastically lower bacterial burdens in their lungs and did not suffer systemic spread of pneumococci. The protective effect of vitamin E correlated with a decrease in neutrophil influx into the lungs. This effect was further modeled in vitro, where vitamin E inhibited neutrophil egress across polarized lung epithelial cells in response to pneumococcal infection. Since neutrophils in excess can be potent mediators of tissue destruction in pneumonia, our findings suggest that vitamin E reverses age‐associated susceptibility to pneumococcus by potentially modulating inflammatory neutrophil influx into the lungs.

Grant Funding Source: Supported by Tufts Collaborates #M230169 and USDA contract #58–1950‐0–014
Linking the pro‐oxidant influences of epigallocatechin gallate (EGCG) to intestinal cholesterol metabolism via alterations in sirtuin 1 (SIRT1) using Caco‐2 cells
Authors: Wegner Casey J , Kim Bohkyung , Yang Yue , Park Youngki , Koo Sung I , Lee Jiyoung
Published: June 2021

The intestine has emerged as a dynamic regulator of whole body cholesterol homeostasis. Pro‐oxidant effects by phenolics may influence intestine‐specific cholesterol regulation. In this study, we link the pro‐oxidant nature of EGCG to its effects on intestinal cholesterol metabolism using Caco‐2 cells. Significant and sustained (0.5–1.5 h) increases in H2O2 formation were observed after EGCG additions to culture media in the absence of cells. This corresponded to a significant increase in reactive oxygen species in Caco‐2 cells after 9 h EGCG treatments (100 μM). EGCG treatments at 50 and 100 μM concentrations decreased mitochondrial DNA copy numbers, which may reflect mitochondrial oxidative damage and/or decreased mitochondrial biogenesis. Nuclear content of SIRT1, a protein deacetylase critically involved in mitochondrial biogenesis, was altered following EGCG treatments. SIRT1 has also been shown to directly deacetylate sterol regulatory element binding protein 2 (SREBP‐2), subsequently reducing SREBP‐2 transcriptional activity. Accordingly, SREBP‐2 target genes, i.e. LDL receptor protein and HMG‐CoA reductase, were upregulated in differentiated Caco‐2 cells after 100 μM EGCG treatments. These results suggest that EGCG‐driven pro‐oxidant effects may alter intestinal cholesterol metabolism by regulating SREBP‐2 activity via SIRT1 inhibition or redistribution.

Grant Funding Source: USDA Hatch
Family Meal (FM) Behaviors and Cognitions among Parents of Preschoolers
Authors: Martin‐Biggers Jennifer , Hongu Nobuko , Worobey John , Byrd‐Bredbenner Carol
Published: June 2021

This study assessed FM behaviors, cognitions, barriers, and methods for coping with barriers of parents of preschoolers. Survey results (n=132) indicate >;50% ate FMs≥6 times/week and≤10% ate FM ≤2/week. Those with high school education or less ate FM significantly less often than those with more education. Days/week on which ≥2 different vegetables were eaten did not differ by education, but those with the most and least education ate ≥2 different fruits significantly less often. The highest education group had sugar‐sweetened drinks significantly less often and were most likely to allow children to decide portion sizes. Nearly all parents looked forward to FMs and valued positive FM environments. Focus group parents (n=25) reported that sharing FMs improved feelings of family connectedness, communications, and food choice healthfulness. Common barriers to FM frequency were time conflicts and differing food preferences of family members. Parents who overcame barriers to FM did so by planning meals and creating FM routines. Common barriers to positive FM environments were stress and eating issues (e.g., picky eaters); parents who overcame these talked about current events, avoided stressful topics, played simple word games at meals, and served foods kids enjoy. Results indicate parents could benefit from interventions that help them have healthier, more frequent, and more positive FMs.

Grant Funding Source: United States Department of Agriculture, National Institute of Food and Agriculture, Grant Number 2011–68001‐30170
Food insecurity and medication utilization in low‐income older Medicare beneficiaries with diabetes
Authors: Sattler Elisabeth Lilian Pia , Lee Jung Sun , Bhargava Vibha
Published: June 2021

Food insecurity (FI) contributes to diet‐related chronic conditions, however little is known about how food insecure older adults manage diabetes. This study examined the relationship between FI and medication utilization among diabetic low‐income older adults using the GA Advanced POMP 6 and Medicare claims data. Participants were enrolled in Medicare Part A and/or B, and D, diagnosed with diabetes, and in need of meals services in GA in 2008 (n=246, mean age 74.1 ±7.8, 66.7% white, 76.4% female). FI was assessed using a 6‐item U.S. HFSSM. Diabetes medication count and treatment intensity were assessed. About 55% were food insecure. This group was more likely younger, socioeconomically disadvantaged, and to report poorer health and medication nonadherence. They were also more likely dually eligible (82.8% vs. 48.2%) and receiving the Medicare Part D subsidy (92.5% vs. 62.5%) than their counterparts. About 29% of the sample did not fill any diabetes medication. Among those filling diabetes medications (range 0–7), 35.8% received oral hypoglycemic monotherapy. Food insecure and secure participants did not show differences in utilization. Our findings suggest that those food insecure may not receive needed medications to adequately manage diabetes. Mismanaged diabetes is avoidable and costly, thus emphasis need to be given to ensure adequate access to care in this population. This study was funded by UGA and GA DAS.