bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Variant R230C Is Associated to a Higher Risk for Hypoalphalipoproteinemia, in School‐aged Mexicans of Hidalgo, Mexico
Authors: Gamo Andrea Gutierrez , Barrera Elizabeth María Tejero , García Marcos Galván , Gamez‐Valdez Elí , Fernández Juan Carlos , Contreras Alejandra Virginia , Rodríguez Guadalupe López 
Published: November 2023

A criteria for Metabolic Syndrome (MetS) is low HDL‐c levels, a frequent trait in Mexico. Additionally to diet and lifestyle patterns, a genetic variant of the ABCA1 gene (R230C) is associated with this, and other metabolic traits in adults. The prevalence of this variant in Mexican mestizos is 10.9%, and is higher in Amerindians (AMI) (8–21%) as compared with other world populations. This variant is associated with low levels of HDL‐c in school‐aged children, although with MetS remains to be determined.ObjectiveTo analyze the association of the R230C variant with anthropometric and biochemical variables, AMI ancestry and MetS by two definitions, in unrelated school‐aged Mexicans of Hidalgo, Mexico. Anthropometric and biochemical data were measured, the R230C variant and 15 ancestry informative markers (AIMs) were genotyped in 735 unrelated Mexican school‐age children aged 4–13 years old, using TaqMan allele discrimination assays. MetS was identified using two definitions (De Ferranti et al (DF), and De Ferranti modified (DFM) in HDL‐c definition).ResultsPrevalence of the MetS was 18.10% and 10.34% using DF and DFM, respectively. The C230 allele was not associated with MetS nor AMI ancestry, as estimated by 15 AIMs (Rho=0.060, p=0.106). The C230 allele was significantly associated with lower levels of HDL‐c (p=0.039) and remained significant after adjustment for gender, age, insulin, HOMA index, AMI ancestry, body mass index (BMI), waist circumference (WC) and waist‐to‐height ratio (C230C,β= −0.063 and R230C,β=0.021, p=0.011,η2=0.013). The main effect of this variant was stronger than BMI (η2=0.007, p=0.022) and WC (η2=0.007, p=0.017). This variant was associated with a higher risk for hypoalphalipoproteinemia (HA) using <35mg/dL (OR=1.66, CI1.143–2.420, p=0.008) and ≤40mg/dL (OR=1.55, CI1.082–2.221, p=0.016) cut‐off points.ConclusionsHA is frequent in school‐aged children of Hidalgo, Mexico using international cut‐off points. The C230 allele is associated with low HDL‐c levels and a higher risk for HA. However, this variant was not associated with MetS or Amerindian ancestry in this study. Cut‐off points for HA may need to be reviewed among different populations and age groups.
Korean Pine Nut Oil Replacement decreases intestinal lipid uptake while improves hepatic lipid metabolism in High‐Fat Diet Fed Mice
Authors: Shuang Zhu , Park Soyoung , Lim Yeseo , Shin Sunhye , Han Sung Nim 
Published: November 2023

Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed with high fat diet (HFD). In this study, we aimed to explore the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed a HFD. Five‐week‐old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO (SC or PC groups), or HFD (45% energy from fat) containing 15% energy fat from lard and 30% energy fat from SBO or PNO (SHF or PHF groups) for 12 weeks. Expression of genes related to intestinal fatty acid (FA) uptake and channeling (Cd36, Fatp4, Acsl5, Acbp), intestinal chylomicron synthesis (Mttp, ApoB48, ApoA4), hepatic lipid uptake and channeling (Lrp1, Fatp5, Acsl1, Acbp), hepatic triacylglycerol (TG) lipolysis and FA oxidation (Atgl, Cpt1a, Acadl, Ehhadh, Acaa1), as well as very low‐density lipoprotein (VLDL) assembly (ApoB100) were determined by real‐time PCR. Overall, replacement of SBO with PNO resulted in significantly less body weight gain (P<0.05). In intestine, PNO‐fed mice had significantly lower Cd36 mRNA expression (P<0.05). ApoA4 mRNA levels were significantly lower in PHF compared with SHF (P<0.05). In addition, PNO consumption tended to result in higher hepatic mRNA levels of Atgl (P=0.08) and Cpt1a (P=0.051). The mRNA levels of Acadl and ApoB100 were significantly higher in mice fed PNO diet (both P<0.05). Together, lower Cd36 and ApoA4 mRNA expression in PNO consumption groups suggest that PNO may decrease activities of intestinal FA uptake and chylomicron assembly in intestine. The tendency of higher Atgl and Cpt1a mRNA expression, together with the significantly higher Acadl and ApoB100 mRNA expression in PNO‐fed group may imply that PNO could increase hepatic TG metabolism; mitochondrial fatty acid oxidation and VLDL assembly. In conclusion, PNO replacement may function to prevent excessive lipid uptake by intestine as well as improve hepatic lipid metabolism in HFD fed mice.Support or Funding InformationSupported by the grant from the National Research Foundation (NRF) of Korea (NRF‐2010‐0024878)
Retroconversion of Docosahexaenoic Acid (22:6n‐3) to Eicosapentaenoic Acid (20:5n‐3) Dominates Over Elongation to 24:6n‐3 in Human Cells
Authors: Park Hi Kyu , Lawrence Peter , Kothapalli Kumar S.D. , Brenna J. Thomas 
Published: November 2023

IntroductionDocosahexaenoic acid (22:6n‐3) is the major omega‐3 fatty acid in the brain phospholipids. It can be consumed in the diet but the details of its metabolic fate are not well defined. Our main objective was to determine whether the neural cell lines handle 22:6n‐3 differently than the visceral tissue derived cell lines.MethodsFour human cancer cells, MCF7 breast cancer, HepG2 hepatocellular carcinoma, SK‐N‐SH neuroblastoma, and Y79 retinoblastoma cells were incubated with albumin‐bound 13C‐22:6n‐3 for 24 h. Cells were harvested after 24 h, fatty acid methyl esters prepared and analyzed by GC‐FID and GC‐covalent adduct chemical ionization tandem mass spectrometry (GC‐CACI‐MS/MS).ResultsThe 13C‐DHA was converted to 13C‐EPA (20:5n‐3) by retroconversion and 13C‐24:6n‐3 by elongation with no synthesis of intermediates 13C‐DPA (22:5n‐3) and 13C‐24:5n‐3 in all four human cells. The conversion of 22:6n‐3 to 20:5n‐3 was much greater in the breast and hepatic cells compared to the neuroblastoma and retinoblastoma cells, suggesting a further mechanism by which high 22:6n‐3 and very low 20:5n‐3 are maintained in neural tissue. The elongation product 13C‐24:6n‐3 was observed in all cells well below 13C‐EPA peak.ConclusionThese results show that the major metabolic transformation of newly imported 22:6n‐3 is a channeled retroconversion to 20:5n‐3 and are consistent with the hypothesis that the efficiency is lower in neural cells.Support or Funding InformationThis work was supported by U.S. National Institutes of Health (NIH) Grant R01 AT007003 from the National Center for Complementary and Integrative Health (formerly the National Center for Complementary and Alternative Medicine) and the Office of Dietary Supplements.
Fat Weight Rises with Increased Severity of Obesity in Women but Not Lean Body Mass
Authors: Babb Tony G , Bernhardt Vipa , Bhammar Dharini , Stickford Jonathon , Basset J. Todd , Marines‐Price Rubria , Roman Maria 
Published: November 2023

PURPOSENot only is fat weight greater in comparisons between nonobese and obese adults but also lean body mass (LBM). In a retrospective analysis, we investigated whether LBM increases with the magnitude of fat weight in obese women. We hypothesized that LBM would increase in proportion to the increase in body size.METHODSAs part of other studies, 207 otherwise healthy obese women between 20 and 45 yr. had body composition determinations by hydrostatic weighing. The subjects were grouped based on their percent body fat (%BF): 1=30≤%BF<40, n=25; 2= 40≤%BF<45, n=54; 3=45≤%BF<50, n=86; and 4=50≤%BF<60, n=42. The groups were compared by ANOVA and the relationships between variables were investigated by regression analysis.RESULTSAge and height were not different among groups. Body weight (kg) was not different between the first two groups, but increased significantly thereafter: 84.6±10.6, 88.0±10.2, 99.4±13.0, and 106.5±14.7, respectively. %BF increased significantly (p<0.0001) among groups 37.2±2.2, 42.9±1.6, 47.4±1.4, 51.7±1.3 (mean±SD), respectively. Fat weight (kg) also increased significantly (p<0.0001) among groups explaining 66% of %BF. However, LBM did not increase or decrease (p>0.1986) with the magnitude of obesity: 52.9±6.2, 50.2±5.9, 52.1±6.7, and 50.7±6.6, respectively, and there was no association between LBM and %BF. There was a modest association between LBM and fat weight (R2=0.28, p<0.001) and height (R2=0.41, p<0.0001). As a percent of body weight, LBM decreased significantly (p<0.0001) with the increase in %BF: 62.7±2.3, 57.1±1.6, 52.4±1.4, 47.7±1.7, respectively.CONCLUSIONSLBM does not increase or decrease with greater classifications of obesity in women. The relationships among %BF, fat weight, and LBM suggest that other factors are involved in the determination of LBM independent of support of fat weight or total body weight.Support or Funding InformationSupported by NIH Grant R01 HL096782, King Charitable Foundation Trust, and Texas Health Presbyterian Hospital Dallas
Assessment of Visceral Adipose Tissue by Dual Energy X‐Ray Absorptiometry and Magnetic Resonance Imaging among a Young Adult Obese Population
Authors: Carpenter Catherine L , Sarma Manoj , Nagarajan Rajakumar , Lee Cathy C , Thomas M Albert , Go Vay Liang , Hahn Theodore J 
Published: November 2023

BackgroundDevelopment of successful weight loss interventions requires accurate assessment of body composition especially when measuring effects of dietary and exercise weight loss approaches. Because increasing proportions of the population are becoming obese, translation of measurement‐rich assessments from the clinical setting into the population setting are essential. Increasing visceral adipose tissue in the intra‐abdominal area during weight gain, independent of total adipose tissue, is associated with cardiovascular disease, metabolic syndrome, type‐2 diabetes, and cancer risk of several sites. The most accurate imaging of visceral fat (VF) is abdominal X‐ray computed tomography (CT) and Magnetic Resonance Imaging (MRI). Dual‐energy X‐Ray absorptiometry (iDXA) with the enCORE™ CoreScan software specifically designed to estimate visceral fat can measure body composition with low radiation exposure and potentially high precision. The iDXA could represent an accurate and less‐expensive option to CT and MRI, although only a few studies have validated iDXA abdominal visceral fat imaging against MRI or CT.Aims and MethodsTo more accurately estimate associations between metabolic parameters associated with adipose tissue, we conducted tandem measurements of abdominal visceral and subcutaneous fat using the MRI and iDXA to determine if iDXA was accurately estimating visceral fat.ResultsA total of 37 subjects, with average age of 28 years old who were mostly female (58%) and Caucasian (62%) had iDXA scans conducted at baseline. On average, they had class 1 obesity (BMI = 38 kg/m2), with average weight of 253 pounds. Their visceral fat averaged 1633 ± 929 grams and total android fat mass was 5531 ± 2160 grams. Of the 37 subjects who had iDXA scans, 13 subjects also had MRI scans within one to two days of the iDXA scan. These 13 subjects had an average MRI assessment of 7918.38±1778.74 cm3 visceral adipose tissue and 12180.08±3702.56 cm3 subcutaneous. Correlations for visceral adipose tissue measurement by both the iDXA and MRI was r=0.59, p=0.04.ConclusionsWhile MRI is the gold standard for assessing visceral abdominal fat, scanning with the iDXA is reasonably accurate. Precision could be improved with a larger sample size.Support or Funding InformationNIH, R01 DK090406
Effects of Endurance and Strength Training and Their Combined Intervention on Body Composition of High School Students
Authors: He Jing , Cui Di , Sun Youping 
Published: November 2023

OBJECTIVETo compare the effects of endurance and strength training and their combination on the body composition of high school students.METHODSSubjects (n=125) were randomized into endurance training (E), strength training (S), combined strength and endurance training (SE), or control group(C) for 18 weeks, 3 times/week, for 25 min. Bioelectrical impedance analysis were perform before and after training.RESULTSBody weight, BMI (Body Mass Index), body fat, body fat rate and muscle mass significantly decreased in E (both P<0.01). Body weight, BMI, body fat and muscle mass significantly increased in S (both P < 0.01), body fat rate increased significantly (P<0.05). Body fat, body fat rate and muscle mass significantly decreased in SE (P < 0.01). Body fat rate decreased significantly in C (P < 0.01).CONCLUSIONEndurance training led to decrease in body weight, BMI, body fat, body fat rate and muscle mass. Strength training led to increase in body weight, BMI, body fat, body fat rate and muscle mass. Strength and endurance combination training led to decrease in body fat, body fat rate and muscle mass.Support or Funding InformationThe key lab of adolescent health intervention and exercise assessment
Terpenoid‐enriched Loquat Leaf Extract Controls the Growth and Survival of Pancreatic Cancer Cell and Acts on Glucose Metabolsim to Alter Pentose Phosphate Pathway
Authors: Lu Qing‐Yi , Yang Jeiping , Go Vay‐Liang , Li Zhaoping , Lee Wai‐Nang 
Published: November 2023

BackgroundEriobotrya japonica (Thunb) Lindl. (Rosaceae), or loquat, is a fruit native to China and Japan. Loquat leaves have been used for the treatment of diabetes mellitus, chronic bronchitis, coughs and skin diseases in traditional Chinese Medicine. The biological active constituents of leaf included terpenoids, which have shown to exhibit anti‐hyperglycemia effect and to promote insulin release by stimulating pancreatic beta‐cells in animal models.AimThe present study investigated novel anti‐tumor activities and the alteration of cellular metabolism by a loquat leaf extract (LLE).MethodThe terpenoid‐enriched extract was prepared by the extraction of dried leaves growing in Southern California with 75% aqueous ethanol. Mia PaCa‐2 pancreatic adenocarcinoma cells were cultured for 48 hours in presence of various concentrations of LLE and its major terpene constituent ursolic acid (UA), and the effect of LLE and UA on the growth and apoptosis of tumor cells was determined. Using 50% [1, 2 13C2]‐glucose as a single precursor metabolic tracer, extracellular lactate production as well as intracellular de novo fatty acid palmitate synthesis, acetyl‐CoA and ribonucleotide ribose were measured.ResultsOur results show that LLE and UA dose‐dependently induce growth suppression and apoptosis, and inhibit phosphor‐AMPK expression. LLE (50 mg/mL) reduces the contribution of glucose to the lactate production and inhibits fatty acid, acetyl‐CoA (P < 0.01) and ribonucleotide ribose (P < 0.01) syntheses. Mass isotopomer analysis also reveals that the treatment of LLE results in marked decrease in pentose cycle flux through the oxidative relative to the non‐oxidative pathway (P < 0.01). Similar results were observed by UA (50 mM) and metformin (1 mM) treatment with the exception that metformin increases lactate production (P < 0.05).SummaryOur study demonstrates that LLE alters glycolysis‐pentose phosphate pathway and controls glucose‐utilizing biomolecule syntheses essential to tumor cell growth and survival.Support or Funding InformationSupported by the Hirshberg Foundation for Pancreatic Cancer Research
Apiaceous Vegetable Intake Modulates Expression of DNA Damage Signaling Pathway Genes and miRNA in Wistar Rats
Authors: Kim Jae Kyeom , Gallaher Daniel D , Trudo Sabrina P 
Published: November 2023

2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) is the most mass abundant heterocyclic aromatic amine in foods and is a colon‐specific carcinogen. We recently showed that PhIP‐DNA adducts in rat colon were reduced by 20% when the diet was supplemented with apiaceous vegetables (i.e., celery and parsnips) at a modest dose (21%, wt/wt) equivalent to a human intake of 1 cup/day (based on a 2,000 kcal diet). The mechanism of action, however, was not through a commonly hypothesized effect, inhibition of pro‐carcinogen activation. Thus, here we examine the effects of apiaceous vegetable intake on promising alternative mechanisms of dietary chemoprevention: 1) N‐methyltransferase (NMT) protein expression, 2) gene expression of PhIP transporters, 3) expression of genes related to DNA damage signaling pathways, and 4) changes in the global microRNA (miRNA) profile in rat colon. Male Wistar rats fed either the American Institute for Nutrition (AIN)‐93G diet (n=6), or the AIN‐93G supplemented with apiaceous vegetables (API; n=7), received a single intraperitoneal injection of PhIP (10 mg PhIP/kg body weight) after 6 days of feeding. A negative control group was fed AIN‐93G and injected with DMSO (n=5). No difference in hepatic NMT protein expression was noted amongst the groups. There was a trend for increased colonic mRNA expression of p‐glycoprotein, a minor PhIP efflux transporter (1.5‐fold; P=0.075); mRNA expression of other colonic PhIP efflux transporters, BCRP and MRP2, was not changed. PCR array analysis revealed that mRNA expression of Pole and Rad18, involved in DNA repair pathways and induced in response to DNA damage, was reduced by API (1.3‐fold for both; P<0.05). Also, in the global miRNA profiling analysis, 11 out of 421 miRNAs were either elevated or suppressed in response to apiaceous vegetable supplementation. In particular, miR‐19b‐3p and miR‐29b‐3p were increased by API diet (2.8‐ and 2.2‐fold increase, respectively, P<0.05). Predictions by Ingenuity Pathway Analysis suggest that these two miRNAs target BMPR2 and CCND1, among others. Some evidence suggests BMPR2 may be oncogenic, and there are reports of a positive correlation between CCND1 overexpression and cancer onset. In conclusion, apiaceous vegetable intake had negligible effects on NMT protein and PhIP transporter gene expression, but did modify genes and miRNA with potential chemopreventive roles. Further investigations are warranted regarding the impact of apiaceous‐mediated modulation of Pole and Rad18, and the net downstream effects of miRNA modulation as pertains to colon carcinogenesis.Support or Funding InformationUniversity of Minnesota Masonic Cancer Center
Synergystic Interaction of Common Bean (Phaseolus vulgaris L.) Peptides and Oxaliplatin on Proliferation of HCT116 Colorectal Cancer Cells through Mitochondrial Depolarization and DNA Damage
Authors: Luna‐Vital Diego‐Armando , DE MEJIA ELVIRA GONZALEZ , Loarca‐Pina Guadalupe 
Published: November 2023

The objectives of this study were to evaluate the antiproliferative effect of common bean (Phaseolus vulgaris L.) peptides on HCT116 human colorectal cancer cells and their interaction with oxaliplatin; furthermore, to determine their potential mechanisms of action. Pure peptides GLTSK, LSGNK, GEGSGA, MTEEY and MPACGS and the peptides in the non‐digestible fraction from common bean cultivars Azufrado Higuera (AH) and Bayo Madero (BM) were tested for cytotoxic effects on HCT116, and also on CCD‐33Co human normal colon cells. None of the peptides were toxic to normal cells at concentrations up to 1 mM. GLTSK (IC50=134.6 μM). On the contrary, according to MTS assay, GEGSGA (IC50=156.7 μM) exerted antiproliferative effects on HCT116 cells.. Based on the combination indexes (γ) of the isobolographic analysis, GLTSK (γ=0.64) and GEGSGA (γ=0.78) interacted synergistically (p < 0.05) with oxaliplatin inhibiting HCT116 cells. Using flow cytometry, it was determined that GLTSK caused loss of mitochondrial membrane potential (Δψm) (16% of cells), increased (p < 0.05) in intracellular reactive oxygen species (ROS) (12.1‐fold compared with untreated cells), cell cycle arrest in G2 (54% of cells) and induced apoptosis (33% of cells). GEGSGA had a limited effect on Δψm and intracellular ROS, but caused arrest in G1 phase (64% of cell population) and promoted increase (p < 0.05) in p53 (290%) and cleavage of PARP (184%) compared to untreated cells, promoting DNA damage. The different mechanisms of action were further established by confocal microscopy. An increase (p < 0.05) in the expression and activation of nuclear p53 (145% of fluorescence intensity/μm2) was observed in response to GEGSGA treatment compared to untreated cells in a time‐frame of 3 to 8 h. Moreover, GLTSK depolarized the cells (38% decrease of fluorescence intensity/μm2) and increased (p < 0.05) intracellular ROS (180% of fluorescence intensity/μm2). In addition, peptide fractions from bean cultivar Azufrado Higuera interacted synergistically with oxaliplatin inducing apoptosis (49% of cells), loss of Δψm (21.7% of cells) and increase of intracellular ROS (13.1‐fold compared to untreated cells). This is the first report demonstrating that dietary peptides from common bean interact synergistically with oxaliplatin inhibiting HCT116 human cancer cells. These results support the hypothesis that physicochemical properties of peptides would determine their mechanism of action.Support or Funding InformationBasic Science, National Council for Science and Technology, Mexico CONACyT‐grant number 220924
1α,25‐Dihydroxyvitamin D3 Inhibits De Novo Fatty Acid Synthesis and Metastatic Capability of Breast Cancer Cells
Authors: Wilmanski Tomasz , Barnard Alle , Donkin Shawn , Parikh Mukti , Buhman Kimberly , Kirshner Julia , Burgess John , Teegarden Dorothy 
Published: November 2023

Breast cancer continues to be the second most commonly diagnosed cancer in American women. Although treatment of localized breast cancer has been effective with five year survival reaching 99%, survival rates drastically decrease to 24% once the tumor has metastasized to distant secondary sites. The most common site of breast cancer metastasis is bone and both higher intracellular lipid accumulation and upregulated de novo fatty acid synthesis correlate with greater breast cell metastatic capability. Therefore, strategies targeting breast cancer cell lipid metabolism may be successful in inhibiting breast to bone metastasis. Here, we demonstrate that the active vitamin D metabolite, 1α,25‐dihydroxyvitamin D (1,25(OH)2D), inhibits the metastatic capability of MCF10CA1a (30% of vehicle) and MDA‐MB‐231 breast epithelial cells (80% of vehicle) in an in vitro 3D (rMET) model of breast to bone metastasis. In addition, we show that 1,25(OH)2D regulates breast cancer cell lipid metabolism by inhibiting de novo fatty acid synthesis from 13C[U]‐Glucose (48%±5.5 relative to vehicle) and decreasing neutral lipid accumulation (BODIPY staining) (56%±7.4 relative to vehicle) at 5 days of treatment. In our studies investigating the mechanisms of 1,25(OH)2D mediated regulation of lipid metabolism, we identified the mitochondrial enzyme pyruvate carboxylase (PC) as a primary target of 1,25(OH)2D. Treatment with 1,25(OH)2D decreased both PC mRNA (58%±7 relative to vehicle) and protein (54%±12 relative to vehicle) expression at 5 days. Consistent with these results, de novo fatty acid synthesis from acetate, the immediate substrate for fatty acid synthesis downstream of glucose, was not changed with 1,25(OH)2D, supporting a role of PC in 1,25(OH)2D mediated inhibition of fatty acid synthesis upstream of lipogenic enzymes. Thus, our studies demonstrate that 1,25(OH)2D decreases fatty acid accumulation and metastatic capability, potentially through downregulation of PC.Support or Funding InformationThis work was supported by a Project Development Team within the ICTSI NIH/NCRR Grant Number UL1TR001108, as well as the National Institutes of Health, National Cancer Institute R25CA128770 (D. Teegarden) Cancer Prevention Internship Program administered by the Oncological Sciences Center and the Discovery Learning Research Center at Purdue University.