bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homocysteine and bone mineral density in older females in the United States (257.5)
Authors: Bailey Regan , Looker Anne , Gahche Jaime , Mills James , Weaver Connie 
Published: June 2021

Previous studies suggest that elevated total homocysteine (tHcy, >13 µmol/L) is a risk factor for bone fracture and osteoporosis; but the data are equivocal and no mechanism has been demonstrated. Elevated tHcy can be caused by impaired renal function, genetic factors, or suboptimal B‐vitamin status. We examined the relationship between tHcy and total body and lumbar spine bone mineral density (BMD) in females 蠅50 years participating in NHANES 1999‐2004(n=2,923). These years had concurrent measurement of tHcy, MMA, RBC folate, serum B‐12, and whole‐body dual‐energy X‐ray absorptiometry. Elevated tHcy was significantly associated with lower total and lumbar BMD when compared to normal tHcy (p <0.001) before and after controlling for age, race/ethnicity, kidney function, BMI, physical activity, intakes of calcium and vitamin D and use of estrogen/progesterone. For example, females with elevated tHcy were more likely to have lumbar spine osteoporosis when compared to females with normal tHcy [OR 2.22 (95%CI:1.3,3.9), p <0.001]. Serum MMA, vitamin B‐12 and RBC folate were not significantly related to BMD. In this population of older females, tHcy appears to be an independent risk factor for low total body and lumbar spine BMD. The role of genetic and other factors that may elevate tHcy concentrations and adversely affect BMD should be explored.Grant Funding Source: Supported by the Office of Dietary Supplements
Correlation between cola consumption and bone mineral density among Puerto Ricans living in the greater Boston area (257.7)
Authors: Jamal‐allial aziza , Tucker Katherine 
Published: June 2021

Correlation between Cola Consumption and Bone Mineral Density among Puerto Ricans Living in the Greater Boston Area Aziza Jamal‐Allial1,Katherine L. Tucker21Health Sciences, Bouvé College of Health Sciences; Northeastern University. Boston, MA. 2Clinical Laboratory &amp; Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA.Several studies have investigated the relationship between the consumption of soft drinks and bone mineral density (BMD), but results are conflicting. We aimed to study the effect of soft drink consumption on BMD at 4 hip sites in 273 men and 698 women in the Boston Puerto Rican Osteoporosis Study using dual‐energy X‐ray absorptiometry (DXA). Soft drink intakes were captured by food frequency questionnaire (FFQ). The mean intake of soft drinks was 2.2 ± 4.3 and 1.5 ± 3.0 servings/week, for men and women, respectively. Total intake of cola beverages was significantly associated with lower BMD at the total hip (β= ‐0.004, P‐value 0.002), trochanter (β= ‐0.003, P‐value 0.03) and femoral shaft (β= ‐0.01, P‐value 0.0005), but not at the femoral neck. Intake of diet‐cola was also significant at the femoral shaft and approached significance at the total hip and trochanter. In contrast, non‐cola soft drinks were not significantly associated with any hip measure. Our models were adjusted for age, sex, BMI, height, calcium‐vitamin D supplement use, dietary calcium intake, smoking, alcohol use, total energy intake, physical activity, and season of BMD measurement. In conclusion, the effect of cola, but not other soft drinks suggests that phosphoric acid may have a negative effect on bone statusGrant Funding Source: This study was supported by the National Institutes of Health grants P01 AG023394, P50 HL105185 and
Supplementation with leucine does not prevent development of obesity in rats fed a high fat diet (258.5)
Authors: Smith Dameon , Washington Tyrone , Davis Gina , Williams Derrick , Baum Jamie 
Published: June 2021

Excess dietary fat consumption has been implicated in the development of obesity and diabetes. Obesity can be characterized by a disproportionate increase in fat mass. However, if muscle mass can be increased or maintained in obesity, this may facilitate weight loss. Historically, supplementation with the branched‐chain amino acid leucine has been shown to increase muscle protein synthesis via the protein kinase mTORC1. Recent studies suggest that supplementation with leucine also has the potential to reduce weight gain and fat deposition in high‐fat fed, obese mice. The objective of this study was to determine if long‐term dietary leucine supplementation prevents development of obesity in rats meal‐fed a high fat (60%) diet. Male, Sprague‐Dawley rats (n=30/dietary treatment) were meal‐fed (3 meals/day) either a control diet (C), control+leucine (CL), high‐fat (HF), or high‐fat+leucine (HFL) for 42 days. On day 42 rats were sacrificed at 0, 30 or 90 minutes postprandial. HF/HFL‐fed rats gained, 28 g more than rats fed C/CL diets (p<0.05). Insulin AUC was 35% higher in CL vs C and 13% higher in HFL vs HF. There was no difference in blood glucose values between treatment groups. Rats supplemented with leucine had significantly higher fat mass and significantly (p<0.05) lower muscle mass compared to their respective controls. However, preliminary data suggest that L and HFL activate translation initiation in muscle via 4E‐BP1 phosphorylation. Taken together, this study demonstrates that supplementation with leucine increases translation initiation, however this does not result in increased muscle mass. Supplementation with leucine does not prevent development of obesity in HF‐fed rats.Grant Funding Source: Supported by Arkansas Biosciences Institute.
Mechanistic studies in swine to evaluate newborn infant vitamin A dosing strategies (260.1)
Authors: Tanumihardjo Sherry , Gannon Bryan , Riabroy Napaporn , Heying Emily , Davis Christopher , Grahn Michael 
Published: June 2021

Clinically, infant care is challenging especially in resource‐poor developing countries where small‐for‐gestational‐age is common and in any country when an infant is born prematurely. Several components comprise perinatal mortality of infants. Children suffering from vitamin A deficiency have a greater risk of irreversible blindness and dying from infectious diseases. Supplementation programs are an approach to address this issue. Studies have found little or no improvement in infant vitamin A status after supplementing with 25,000 IU vitamin A. Based on WHO’s recommendations, children ages 6 ‐ 11 mo receive 100,000 IU vitamin A and those 12 ‐ 59 mo receive 200,000 IU vitamin A every 4 to 6 mo. Multi‐centered and randomized trials of infant supplementation programs have shown inconsistent results. Infant supplementation itself has been debated due to the higher incidence of bulging fontanelle in vitamin A‐dosed infants. Therefore, a series of studies were performed in a swine model to evaluate infant dosing regimens. Newborn piglets from vitamin A‐depleted sows received a placebo, 25,000, 50,000, or 200,000 IU vitamin A supplements at birth. Tissues were collected and analyzed. The degree of vitamin A deficiency did not seem to affect the response to treatment. High doses may be quickly catabolized to maintain balance. Lung and spleen require chylomicron vitamin A to maintain concentrations, which was confirmed with a tracer study using α‐retinol. The tracer study also showed quick uptake in the adrenal gland. Low birth weight piglets took up less vitamin A. Food sources of vitamin A performed better than supplementation at improving vitamin A status of offspring.Grant Funding Source: Supported by the Nutrition Unit at the World Health Organization.
Vitamin D status is linked with plasma glutathione and cysteine thiol/disulfide redox status in adults (260.4)
Authors: Alvarez Jessica , Chowdhury Ritam , Jones Dean , Martin Greg , Brigham Kenneth , Binongo Jose , Ziegler Thomas , Tangpricha Vin 
Published: June 2021

Objective: Redox status and inflammation are important in the pathophysiology of numerous chronic diseases. Epidemiological studies have linked vitamin D nutriture to a number of chronic diseases. We examined the relationships between serum 25‐hydroxyvitamin D (25(OH)D) concentrations and circulating biomarkers of redox and inflammation.Methods: We studied a community‐based cohort of working adults in Atlanta, GA (N=693). Plasma thiol/disulfide redox status was determined by HPLC [glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CySS), and their calculated redox potentials (Eh), calculated by the Nernst equation]. Pro‐inflammatory biomarkers included IL‐6, IL‐8, TNF‐α, and C‐reactive protein. Relationships were assessed by multiple linear regression.Results: Serum 25(OH)D levels were positively associated with plasma GSH levels, a more reducing GSH/GSSG EhCys, and inversely with Cys levels (P<0.001). These associations were not influenced by subject age, gender, race, % body fat, and cardiovascular risk factors (P<0.02). Serum 25(OH)D was not independently associated with any inflammatory marker.Conclusion: Serum 25(OH)D levels were independently associated with major plasma thiol/disulfide redox systems, suggesting that vitamin D status may be involved in redox‐mediated pathophysiology.Grant Funding Source: Supported by NIH (T32DK007298, UL1TR000454, K23AR054334, and K24RR023356).
SIRT1 dependent IRS1 phosphorylation mediates the effect of vitamin D on GLUT4 translocation and glucose utilization via PI3K/PTEN/PTP1B/ PIP3/AKT/PKCζ/λ signaling cascade in high glucose treated 3T3L1 adipocytes (260.5)
Authors: Manna Prasenjit , Jain Sushil 
Published: June 2021

This study examined the biochemical mechanism by which VD regulates glucose homeostasis in diabetes. 3T3L1 adipocytes were treated with VD (1,25(OH)2D3, 0‐50 nM, 2 h) and high glucose (HG, 25mM, 20 h). Results (n=4) showed that VD upregulated SIRT1 protein expression and IR phosphorylation, stimulated IRS1/PI3K/PTEN/PTP1B/PIP3/AKT/PKCζ/λ signaling cascade, and increased GLUT4 translocation (44%), and glucose utilization in HG treated cells. VD also upregulated its receptor (VDR) protein expression (45%) and decreased ROS (31%), NOX4 protein expression (71%), and NF‐κB phosphorylation (47%) in HG treated cells. VD treatment along with insulin enhanced GLUT4 translocation (29%) and glucose utilization (32%) compared to either insulin or VD alone in HG treated cells. Signal silencing studies showed that in IR siRNA transfected cells, VD can increase the IRS1 phosphorylation, GLUT4 translocation, and glucose utilization; however the effect of VD was significantly inhibited in the SIRT1 siRNA transfected cells. Studies with VDR siRNA demonstrated that the effect of VD on glucose metabolism in HG treated cells is mediated via its receptor. This study demonstrates a novel molecular mechanism by which VD upregulates SIRT1 protein expression and IRS1 phosphorylation which mediate the GLUT4 translocation and glucose utilization via PI3K/PTEN/PTP1B/PIP3/AKT/PKCζ/λ signaling cascade in adipocytes.Grant Funding Source: Supported by NIH RO1 AT007442 and Malcolm Feist Chair in Diabetes
Prohibitin1 regulates H19 and insulin‐like growth factor 2 expression in hepatocytes and liver (261.1)
Authors: Ko Kwang Suk , Yang Heping , Li Tony , Lee Sang Hoon , Song Young Sun , Lu Shelly 
Published: June 2021

BACKGROUND&AIMS: Prohibitin1 (Phb1) is a ubiquitously expressed and highly conserved protein that acts as a mitochondrial chaperone and possibly as a tumor suppressor in liver. We reported liver‐specific Phb1 knockout (KO) mice develop multifocal hepatocellular carcinoma (HCC) and knockdown of Phb1 in AML12 cells (a normal hepatocyte cell line) accelerated growth. H19 and insulin‐like growth factor 2 (Igf2) are two imprinted genes often overexpressed in HCC that are induced in the Phb1 KO livers. Here we examined how Phb1 regulates their expression. METHODS: Real‐time PCR and Western blotting measured expression in Phb1 KO livers and AML12 cells treated with various siRNAs. RESULTS: H19 RNA and Igf2 mRNA and protein levels are tremendously upregulated with Phb1 deficiency in vivo (by several hundred folds) and in vitro (2‐fold after 24 hour Phb1 siRNA treatment). E2F1 and c‐Myc can activate H19 transcriptionally, but knockdown or either c‐Myc or E2F1 did not block H19 or Igf2 induction with Phb1 knockdown. Ctcf, an insulator protein that represses Igf2 expression when it is bound to the imprinting control region, is downregulated with Phb1 knockdown in AML12 cells. Double knockdown of Phb1 and Ctcf resulted in the same magnitude of H19 and Igf2 induction as single knockdown of either Phb1 or Ctcf, suggesting Phb1 may regulate the expression of H19 and Igf2 through Ctcf. Interestingly Ctcf expression is lower while H19 and IGF2 are induced in HCC samples as compared to normal liver. CONCLUSIONS: Loss of Phb1 lowers Ctcf expression, which in turn allows H19 and Igf2 gene induction to occur.Grant Funding Source: Supported by NIH R01 (R01CA172086) and NRF Korea Fund (2012R1A1A1012261)
The role of sirtuin 3 in the differential pro‐oxidant effects of (‐)‐epigallocatechin‐3‐gallate in oral cells (261.4)
Authors: Tao Ling , Lambert Joshua 
Published: June 2021

Dietary approaches may play an important role in reducing oral cancer burden. The green tea catechin, (‐)‐epigallocatechin‐3‐gallate (EGCG), has been reported to have cancer preventive effects. Previously, we found that EGCG induced mitochondrial dysfunction, oxidative stress and apoptosis in oral cancer cells but exerted antioxidant effects in normal oral cells. In this study, we aim to investigate the role of sirtuin 3 (SIRT3), an important mitochondrial redox balance regulator, in EGCG‐induced differential pro‐oxidant effects in oral cells. We found 100 µM EGCG significantly decreased SIRT3 mRNA (15%‐56%; 1‐12 h) and protein levels (17%‐34%; 6‐24 h), as well as, activity (58%; 12 h) in SCC‐25 oral squamous carcinoma cells. By comparison, there was no significant effect of EGCG on SIRT3 mRNA and protein levels, but a remarkable increase of SIRT3 activity (7.5‐fold; 12 h) in HGF‐1 human gingival fibroblast cells. The estrogen‐related receptor alpha (ERRα) regulates transcription of SIRT3. EGCG significantly decreased the mRNA (20%‐44%; 3‐6 h) and protein levels (31%‐50%; 6‐24 h) of ERRα in SCC‐25 but not HGF‐1 cells, indicating that EGCG regulates SIRT3 expression through modulation of ERRα. The effect of EGCG on transcription activity of ERRα is under investigation. This study identified SIRT3 as a novel target of EGCG, thus providing additional mechanistic information for future in vivo studies.Grant Funding Source: Supported by a grant from the American Institute for Cancer Research (Grant #10A102 to JDL)
Needs assessment for childhood obesity intervention program (262.1)
Authors: Harper Kristin , Berenson Danielle , Calkin Katie , Buffalo Julie , Mullis Rebecca , Anderson Alex 
Published: June 2021

The purpose of this study was to assess the needs of families of obese children to inform the development of a clinic‐based program to manage the weight and health of obese children. This cross‐sectional study assessed selected nutritional and behavioral habits and the family environment of obese children who were seen in a private pediatric practice. Primary caregivers of 20 obese children were interviewed via phone using a structured questionnaire containing closed‐ and open‐ended questions. Descriptive statistics were used for data analysis with results reported as percentages and means. The mean age of the children was 9.2±2.9 yrs. The majority of the children (55%) were males. Seventy‐five percent of the parents/guardians spoke Spanish as the primary language. Mean fruit and vegetable intake was 3.2±1.9 servings/d. Three‐quarters of children were reported to consume sugar‐sweetened beverages, with a mean intake of 1.9±1.6 cups/d. Although caregivers reported their children played actively for an average of 54.3 min/d, the majority of the children spent over 2 hrs on screen time. About 90% of parents/caregivers reported that they are currently working on changing their children’s dietary and health habits. Our preliminary results suggest a need for clinic‐based program with emphasis on improving nutritional and behavioral habits of obese children and their families while ensuring it is culturally relevant.Grant Funding Source: Supported by: The William B. Mulherin Foundation for Health & Wellness
Maternal vitamin D status during pregnancy is associated with infant anthropometry during the first year of life (267.1)
Authors: Eckhardt Cara , Gernand Alison , Roth Daniel , Bodnar Lisa 
Published: June 2021

Maternal vitamin D deficiency during pregnancy has been linked to fetal growth and may also impact child growth in infancy. We used data and blood samples from the 12‐site U.S. Collaborative Perinatal Project (1959‐65) to examine the association of maternal vitamin D status during pregnancy and infant anthropometry across the first year of life in singletons (n=2473 mother‐child pairs). Maternal serum 25‐hydroxyvitamin D (25(OH)D) was measured at 蠄26 weeks gestation using chromatography‐tandem mass spectrometry. Infant anthropometry was expressed as z‐scores for length (LAZ), head circumference (HC‐Z), weight (WAZ), and BMI (BMI‐Z) based on measures at birth and 4, 8 and 12 months of age. We controlled for study site, and important infant and maternal characteristics in linear mixed effects models. 25(OH)D <30 nmol/L (conventional definition of deficiency) vs. 蠅30 nmol/L was associated with LAZ and HC‐Z measures that were 0.13 (95% CI: 0.03‐0.23) and 0.20 (95% CI: 0.11‐0.28) lower, respectively, across the first year of life. Differences observed by 25(OH)D in WAZ and BMI‐Z at birth resolved by 4 months of age, potentially reflecting catch‐up growth. These findings suggest that maternal vitamin D deficiency has a sustained association with markers of linear or skeletal growth during the first year of life, while initial associations with measures of weight and body composition may resolve.Grant Funding Source: Supported by R01 HD 056999
Diet patterns and clustering of cardiometabolic risk during adolescence (267.5)
Authors: Moore Lynn , Singer Martha , Bradlee M. , Daniels Stephen 
Published: June 2021

Objective: To examine the relation between adolescent dietary patterns and cardiometabolic risk (CMR) clustering at end of adolescence.Methods: Data for 1369 girls enrolled at 9‐10 years of age in the longitudinal NHLBI Growth and Health Study were used. Girls with complete data over 10 years on diet, and six CMR factors, and all confounders of interest were included. Mean dietary data were derived from 3‐day records. CMR factors analyzed included increased waist circumference, elevated blood pressure, insulin resistance, low HDL‐cholesterol and high LDL‐cholesterol and triglyceride levels. Multiple logistic regression analysis was used to estimate the relative risk of having multiple (蠅 2 or 蠅 3) risk factors in late adolescence associated with usual dietary patterns from 9‐17 years of age.Results: Of 1369 subjects included, 252 (18.4%) had 3‐6 risk factors while 479 (35.0%) had two or more. Higher intakes of fruit and non‐starchy vegetables, dairy, and grains were independently associated with having fewer risk factors as were eating patterns characterized by higher combined intakes of these food groups. After adjusting for age, race, socio‐economic status, height, physical activity, and television watching, girls with high intakes of both dairy and fruits and non‐starchy vegetables (vs. lower intakes) were nearly 50% less likely to have 蠅 3 CMR factors while girls with higher intakes of grains and fruits and non‐starchy vegetables (vs. lower intakes) were nearly 60% less likely to have 蠅 3 CMR factors.Conclusion: These data suggest that CMR clustering at the end of adolescence is associated with dietary patterns during adolescence.
Dietary cholesterol and heart health: a systematic review and meta‐analysis (267.6)
Authors: Berger Samantha , Raman Gowri , Vishwanathan Rohini , Jacques Paul , Johnson Elizabeth 
Published: June 2021

Objectives: To conduct a systematic review and meta‐analysis evaluating the effects of dietary cholesterol on cardiovascular outcomes in healthy adults.Methods: Medline, Cochrane Central, and CAB databases were searched through March 31, 2013 for prospective studies in English‐language that quantified dietary cholesterol and cardiovascular or lipid outcomes in adults. Random effect models meta‐analysis was used when at least 3 studies reported the same outcome.Results: 28 studies (16 cohorts with 361,923 subjects and 9 randomized trials with 579 subjects) published between 1981 and 2013 were eligible. Dietary cholesterol was not significantly associated with ischemic heart disease deaths (4 cohorts, summary relative risk [RR] 1.35, 95% CI 0.91, 2.01) or ischemic stroke (4 cohorts, summary RR 1.13, 95% CI 0.99, 1.28). Dietary cholesterol intake 蠅300mg/day compared to <300 mg/day, had a small but statistically significant increase in plasma total cholesterol (9 trials, net change 6.76 mg/dL, 95% CI 0.71, 12.80, p=0.029) and LDL cholesterol (9 trials, net change 5.41 mg/dL, 95% CI 0.62, 10.20, p=0.027), but no significant change in HDL cholesterol.Conclusions: Reviewed studies were heterogeneous and lacked methodological rigor. Carefully controlled efficacy studies and well‐conducted cohort studies may still be useful to pin down the relative effects of dietary cholesterol on cardiovascular outcomes.Grant Funding Source: This study is supported by the Egg Nutrition Center
Nicotinic acid synergizes with leucine to stimulate AMPK/Sirt1 signaling and regulates lipid accumulation and lifespan in C. elegans (269.7)
Authors: Bruckbauer Antje , Zemel Michael 
Published: June 2021

Previous data demonstrate the BCAA leucine (Leu) to stimulate AMPK and Sirt1 signaling in vitro and in vivo. Nicotinic acid (NA) has been used as a highly effective treatment of dislipidemias; however, its poorly tolerated side effects (severe vasodilation and flushing at high doses) limits its use as a drug. Since it increases NAD+ and thereby activates Sirt1, we tested the synergistic effects of leucine (0.5 mM) and low dose NA (10 nM) on AMPK/Sirt1 signaling and downstream effects in cell culture and C. elegans. The NA‐Leucine combination increased P‐AMPK by 80%, P‐AMPK/AMPK ratio by 114% (p<0.001) and Sirt1 by 25% (p=0.04) in adipocytes and myotubes, while the individual components exerted no independent effect. In C. elegans, NA‐Leu increased P‐AMPK and DAF‐16 (FOXO) signaling by 66% (p=0.018) and 105% (p=0.004), respectively. This was associated with a reduction in lipid accumulation by 49% (p=0.017) and a 28% increase in median survival (p=0.0001) under mild oxidative stress conditions (0.2 mM paraquat). These data indicate that low concentrations of NA synergize with leucine to modulate sirtuin signaling and lipid metabolism, and may therefore be a potential therapeutic for treatment of metabolic diseases.Grant Funding Source: NuSirt Sciences Inc.