bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folic Acid Content in Gestational Diet Elicits Dose‐dependent Changes on Hypothalamic Feeding Circuits in Wistar Rats at Birth
Authors: Yang Neil Victor , Chatterjee Diptendu , Pannia Emanuela , Kubant Ruslan , Anderson Gerald Harvey 
Published: November 2023

BackgroundFolate plays an important role in early brain development of offspring, notably on neural stem cell proliferation and differentiation. Excess (10‐fold) intakes of folic acid (FA) in the gestational diet have been linked to increased food intake and obesity in adult offspring. Hypothalamic neuronal populations play a critical role in regulating food intake and maintaining energy balance.ObjectivesTo identify neuronal populations susceptible to FA intakes during pregnancy, we measured the expression and maturation of neuropeptide Y (NPY+) and proopiomelanocortin (POMC+) containing neurons, known to induce opposing effects on food intake regulation. Furthermore, we tested if these outcomes could be explained by altered folate metabolism in the brain, which could lead to epigenetic reprogramming of neuronal differentiation and maturation.Methods and DesignPregnant Wistar rats were assigned to one of 5 AIN‐93G diets (n=12/group) providing FA at: 0, 1.0 (control), 2.5, 5.0, or 10.0‐fold of recommended level. Expression of NPY and POMC neuronal populations were assessed in coronal hypothalamic sections from male rat offspring, collected at birth. Immunohistochemical staining for the neuronal nuclear antigen (NeuN) measured neuron quantity and maturation. Hypothalamic levels of folate metabolites were assessed by HPLC analysis.ResultsA dose‐dependent effect (P <0.05) was identified between higher intakes of gestational FA and increased expression of mature NPY‐containing neurons in the hypothalamus, at birth. Pups from 2.5‐ and 5.0‐fold FA groups had 2.2 and 3.1‐fold more mature NPY‐neurons than control, respectively. However, gestational FA content had no effect on the number and maturation of POMC‐expressing neurons. Deficient (0‐fold) and high (10.0‐fold) FA gestational diets lead to higher levels of tetrahydrofolate (THF, 2.4 fold, P <0.0001) and 5‐methyltetrahydrofolate (MTHF, 3–4 fold, P <0.0001) in the hypothalamus, compared to control.ConclusionFA content in the gestational diet elicits a dose‐dependent effect on the number of mature hypothalamic NPY neurons in male Wistar rats at birth, possibly associated with greater accumulation of folate metabolites in the brain. This indicates that hypothalamic food intake pathways are sensitive to the dose of gestational FA and its bioactive metabolites, which may influence metabolic phenotype of offspring later in life.Support or Funding InformationCanadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes (CIHR‐INMD), Reference MOP‐130286.
Racial/ethnic disparities in childhood body mass index trajectories and potential causes among 29,254 US children: the Early Childhood Longitudinal Study‐Birth and Kindergarten Cohorts
Authors: Wang Youfa , Min Jungwon , Wen Xiaozhong , Xue Hong 
Published: November 2023

ObjectiveDescribe recent sex‐ and ethnic‐specific childhood BMI growth trajectories of US children, and explore the potential causes of racial/ethnic disparities in childhood BMI trajectories, including household socio‐economic status (SES) and family rules for children's TV watching, bedtime, and meal time.MethodsThe sex‐ and ethnic‐specific children's mean BMI trajectory curves between 7 months to 16 years of age were fitted by mixed effect models with fractional polynomial functions using 29,254 children from two US nationally representative cohorts, Early Childhood Longitudinal Study Birth (ECLS‐B, 2001) and Kindergarten (ECLS‐K, 1998–99). Multivariate regression model was used to examine the mediating roles of household SES and family rules on racial/ethnic disparities in childhood BMI trajectory characteristics.ResultsHispanic boys (HB) and African American girls (AAG) continuously had the highest mean BMI after adiposity rebound than their same sex counterparts. They had the earliest adiposity rebound (mean [SD]: HB‐57.9 [7.8]; AAG‐59.0 [7.2] months), steeper growth velocity (HB‐5.7 [1.8]; AAG‐7.0 [1.5] 10−2 kg/m2/month), and highest area under curve (HB‐2724.5 [489.8]; AAG‐2681.2 [426.7] kg/m2*month) from adiposity rebound to 16 years of age. The racial/ethnic disparities in childhood BMI trajectories were partially mediated by household SES and family rules for children's regular bedtime (p<0.05).ConclusionsIn the US, racial/ethnic disparities in childhood BMI trajectories are apparent starting from adiposity rebound. Hispanic boys and African American girls have unfavorably high BMI trajectories. These disparities can be substantially explained by household SES level and family rules for children's bedtime. Efforts to reduce obesity disparities in different races/ethnicities should start early and focus on preventing early life risk factors related to sociodemographic characteristics and family rules for children's daily routine.Support or Funding InformationNIH, 1R01HD064685‐01A1
Loss of a Healthy Weight Advantage among Foreign‐born Children of Mexican Origin: An Analysis of Overweight/Obesity Trends from 1988–1994 to 2007–2014
Authors: Maldonado Luis E. , Albrecht Sandra S. 
Published: November 2023

We evaluated whether foreign‐born Mexican‐American (MA) children continued to exhibit a health weight advantage in recent years relative to U.S.‐born MA children given Mexico's emerging obesity epidemic. We also investigated the implications of these changing patterns on overweight/obesity disparities between MAs and non‐Hispanic whites (NHW) over time. Using data from MA and NHW children ages 5–17 years participating in the National Health and Nutrition Examination Surveys (1988–1994 (N=4,022) and 2007–2014 (N=4,713), we calculated odds ratios (OR) of overweight/obesity by ethnicity‐nativity (US‐born MA, foreign‐born MA, and NHW), adjusting for socio‐demographic covariates, and an interaction between ethnicity‐nativity and survey period. In 1988–1994, foreign‐born MAs had significantly lower adjusted odds of overweight/obesity compared to US‐born MAs (OR = 0.53, 95% CI: 0.33, 0.85). However, by 2007–2014, the nativity gap in overweight/obesity closed (OR = 0.85; 95% CI: 0.65, 1.11), indicating that the healthy weight advantage once held by foreign‐born MAs was no longer evident in recent years. Moreover, although predicted probabilities estimated from logistic regression models suggested foreign‐born MAs had the lowest predicted probability of overweight/obesity (25%) in 1988–1994 compared to both US‐born MAs (39%) and NHW children (32%), by 2007–2014, foreign‐born and US‐born MAs had comparable estimates (60% and 64%, respectively), both higher than for NHW's (57%). The healthy weight advantage previously held by foreign‐born MA children appears to have eroded in recent years. Although disparities in childhood overweight/obesity between MAs and NHWs had previously been specific to US‐born MAs, disparities in recent years have extended to foreign‐born MAs. Continued monitoring of overweight/obesity trends in foreign‐born MA children, as well as those born in the US, is critical given the long‐term impacts on cardio‐metabolic outcomes, which already disproportionately burden Mexican‐Americans adults.Support or Funding InformationNIH/NHLBI (1‐T32‐HL129969‐01A1) and the Carolina Population Center (R24 HD050924)
Evaluation of ‘JenMe’, a Commercially‐Delivered Weight Management Program for Adolescents: a Randomised Controlled Trial
Authors: Bonham Maxine P , Dordevic Aimee L , Ware Robert S , Truby Helen 
Published: November 2023

ObjectiveAdolescent obesity is difficult to treat and widely accessible treatment options with proven efficacy remain scarce. This study evaluated a commercially available, structured short‐term weight management program designed for obese adolescents delivered by non‐health professionals.MethodsA multi‐site parallel‐group randomised controlled trial was conducted to evaluate a commercial 12 week lifestyle behavioral program in commercial weight management centres in Australia. Eligible participants (13–17 years, BMI z score ≥1.282 with no presenting morbidities) were randomized (n=88) to intervention or wait‐list and the program was delivered by consultants at participating weight management centres. The primary outcome was change in BMI z score. Secondary outcomes included the psychometric variables quality of life, body esteem and self‐esteem. Data was analyzed according to intention‐to‐treat principles.ResultsOf 88 participants randomised, 74 enrolled into the program and 12‐week data was available for 55 individuals (74%). A significantly greater decrease in BMI z‐score in the intervention group (n=32) was observed when compared with the wait‐list control group (mean difference (MD) = −0.27 kg/m2; 95% confidence interval [CI], −0.37, −0.17; P<0.001). Participants allocated to receive the lifestyle intervention reported a greater improvement in body esteem (MD=2.3, 95%CI, 0.6, 4.1; P=0.009) and quality of life (MD=7.8, 95%CI, 1.6, 14.0; P=0.01) compared with the wait‐list control group. Similarly, intervention group participants had greater physical activity levels (MD=0.09 metabolic equivalents, 95%CI, 0.02, 0.17; P=0.03) compared with the wait‐list control group.ConclusionsThis evaluation provides evidence that a structured lifestyle intervention delivered by a commercial provider in an adolescent population can result in clinically relevant weight loss and improvements in psychosocial outcomes in the short term. Further research is required to evaluate long term outcomesSupport or Funding InformationThe study was funded by Jenny Craig Weight Loss Centres Pty Ltd as a research grant to A/Prof Bonham and Prof Truby. By contractual agreement, scientists (MB, HT, AD) at Monash University and other participating institutions (RW) have responsibility and independence regarding data management, analysis and publication.
Untargeted Metabolomics Reveal Disparate Metabolite Profile in Follicular Fluid between Obese and Normal Weight Women
Authors: Ruebel Meghan L , Piccolo Brian D , Moutos Dean M , Shankar Kartik , Andres Aline 
Published: November 2023

The microenvironment of follicular fluid is thought to provide a rich source of nutrients and other factors that promotes oocyte growth and viability; however, it is not known if obesity or related sequelae impacts this environment. To address this research gap, we designed a clinical study to assess follicular fluid metabolite profiles, inflammatory markers and oocyte gene expression. Normal weight women (NW; n=13) and overweight/obese (OW; n=11) undergoing fertility treatments were recruited prior to an oocyte retrieval procedure. Anthropometrics, body composition (Air Displacement Plethysmography), and overnight fasting serum samples were collected. During the oocyte retrieval procedures, follicular fluid aspirates containing the oocyte samples were also collected. Leptin, C‐reactive protein, triglycerides, and total cholesterol were assessed in serum and follicular fluid using colorimetric and ELISA assays. Gas chromatography time of flight‐mass spectrometry was used to characterize the metabolome of serum and follicular fluid. Discriminant metabolites of NW and OW samples were identified using a backwards iterative selection strategy using ranked variable importance in projection measurements from partial least squared‐discriminant analysis (PLS‐DA) models. By design, OW women had significantly higher BMI, fat mass, and serum HOMA‐IR compared to NW women (p<0.01). Leptin and C‐reactive protein concentrations were increased in both serum (5.3±1.0 vs. 27.2±6.6 and 3.2±0.7 vs. 5.7±1.0, respectively) and follicular fluid (11.1±2.4 vs. 26.8±6.7 and 2.7±0.8 vs. 5.9±1.8, respectively) from OW women and follicular fluid triglyceride (25.8±14 vs. 64.2±46.9, respectively) and total cholesterol (21.1±3.2 vs. 36.3±7.6, respectively) levels were elevated in OW women compared to NW (p<0.05) women. Metabolites selected as discriminant of NW and OW follicular fluid samples by PLS‐DA included elevated uric acid, isothreonic acid, 2‐deoxytetronic acid and 4 unknown metabolites in OW women. Conversely, 2‐dimethylacetal‐ketoglucose, aminomalonate, and 2 unknown metabolites were significantly decreased in OW relative to NW women. Other serum metabolites discriminant of NW and OW serum included cholesterol, mannose, palmitic acid, sucrose, and 5 unknown metabolites. These results suggest that the follicular fluid metabolome differs between NW and OW women and may potentially contribute to altered oocyte metabolism and development. One unknown metabolite, BB112556, was significantly lower in both follicular fluid and serum, raising the possibility of a serum biomarker of oocyte health and development. Combined with previous findings of differential oocyte gene expression in NW vs. OW women from this cohort, these results suggest that obesity significantly affects oocyte transcription and follicular fluid metabolites.Support or Funding InformationACHRI CUMG 035716 and USDA□ARS Project 6026□51000□010□05S
Nicotinamide Riboside, an NAD+ Precursor, Attenuates The Activation of Hepatic Stellate Cells
Authors: Pham Tho X. , Bae Minkyung , Lee Ji‐Young 
Published: November 2023

Recent evidence suggests that supplementation of nicotinamide riboside (NR), a natural NAD+ precursor found in milk, can reduce liver fibrosis in several mouse models of non‐alcoholic steatohepatitis. However, the molecular mechanism by which NR reduces liver fibrosis remains to be elucidated. Hepatic stellate cells (HSCs) are primarily responsible for the production and deposition of collagen and other extracellular matrix (ECM) substances in the liver during injury. Upon liver injury, HSCs become activated and transdifferentiate into a‐smooth muscle actin (aSMA)‐positive myofibroblasts, which produce ECM proteins such as collagen 1a1 (COL1a1). Therefore, we determined whether the preventive effect of NR on liver fibrosis is attributed to its effect on the activation of HSCs. LX‐2 cells, a human HSC cell line, were pretreated with or without 500 mM of NR for 24 h followed by treatment of 4 ng/mL of transforming growth factor β1 (TGFβ1), a potent pro‐fibrogenic cytokine, for an additional 24 h in the absence or presence of NR. TGFβ1 markedly increased the protein levels of aSMA and COL1a1, while NR pretreatment significantly attenuated the TGFβ1‐induced increase in COL1a1 protein levels. Despite the reduction in COL1a1 protein by NR, its mRNA levels were significantly increased by NR, suggesting that NR may regulate COL1a1 expression at the post‐transcriptional level in LX‐2 cells. We next isolated mouse primary HSCs from C57BL/6 mice and activated them by culturing on a plastic dish for 7 days in the absence or presence of 500 μM NR. Compared to mouse primary HSCs cultured for 2 days, which maintain their quiescent state, HSCs activated for 7 days expressed significantly higher levels of aSMA and COL1a1 mRNA. When NR was added to HSCs during the activation for 7 days, aSMA and COL1a1 mRNA levels were significantly lowered when compared to the cells that were activated in the absence of NR. This suggests that NR treatment attenuated the activation of quiescent mouse primary HSCs to myofibrolasts. Together, we demonstrated that treatment of NR attenuated HSC activation in human and mouse models of HSCs, which suggests that anti‐fibrotic action of NR in the liver may be attributable, at least in part, to its inhibitory effect on the activation of HSCs.Support or Funding InformationUSDA Hatch CON00972
Twenty‐Four‐Hour Urine Phosphorus is Highly Variable in Patients with Moderate Chronic Kidney Disease on a Controlled Phosphorus Intake
Authors: Stremke Elizabeth R. , McCabe Linda D. , McCabe George P. , Martin Berdine R. , Wastney Meryl , Moe Sharon M. , Weaver Connie M. , Peacock Munro , Hill Gallant Kathleen M. 
Published: November 2023

Twenty‐four‐hour urine phosphorus (24h uP) is commonly considered a good reflection of dietary phosphorus (P) intake in healthy adults in P balance because net absorption of P is linearly related to dietary intake over a wide range of intakes. This relationship has been assumed to also apply to patients with chronic kidney disease (CKD). However, factors other than dietary P intake and intestinal P absorption may affect 24h uP excretion, including the rate of net bone retention and soft tissue P deposition and retention. This study is a secondary analysis of the variation in 24‐hour urine phosphorus and its reliability as a measure of phosphorus intake in patients with moderate chronic kidney disease. Thirteen consecutive 24‐hour urines from 2‐week balance studies in 8 patients with estimated glomerular filtration rates 26–53 mL/min/1.73m2 on a tightly‐controlled dietary phosphorus intake of 1564 ± 52 mg/d were analyzed for variability and reliability. Results show, while consuming a controlled P diet, there is wide day‐to‐day intrasubject (standard deviations from 105–208 mg/d or %CV 15–60) and intersubject variation in 24h uP (standard deviation of 267 mg/d or %CV =37), as well as phosphorus/creatinine ratio. Intraclass correlation coefficients were calculated for 24h uP (r = 0.65) and phosphorus/creatinine ratio (r = 0.60). From these values, it was estimated that the number of replicates needed to have at least 75% reliability for 24h uP or P/Cr is 2 (95% CI: 1,5), and more replicates if a greater degree of reliability is desired. While 75% is generally considered a threshold for an acceptable level of reliability, the 13 replicates that were available from these balance studies gave over 90% reliability in the measures of both 24h uP and P/Cr. Dietary phosphorus intake calculated from 24‐hour urine phosphorus underestimated intake in some patients by up to 98% and overestimated intake in others by up to 79%. In patients with moderate chronic kidney disease, 24h uP is highly variable and its use can lead to erroneous conclusions regarding dietary phosphorus intake.Support or Funding InformationThe parent study was a randomized controlled trial funded by Sanofi/Genzyme through an unrestricted investigator‐initiated grant to MP, and, in part, by a NCRR Clinical and Translational Sciences Award (U54‐RR025761, Shekhar, PI). This secondary analysis was supported through institutional funds of KMHG. KMHG is supported by NIH K01 DK102864.
Mixture of Oleanolic acid and Ursolic Acid Mimicked the Effects of Fructus Ligustri Lucidi on Calcium Kinetics, Bone Properties, and Serum 1,25(OH)2D3 in Ovariectomized Rats
Authors: Wong Man Sau , Cao Si Si , Wastney Meryl E. , Lachcik Pamela J. , Weaver Connie 
Published: November 2023

Oleanolic acid (OA) and ursolic acid (UA) are major chemical constituents in Fructus Ligustri Lucidi (FLL), a Chinese herb previously shown to improve calcium balance and bone properties in rats. OA and UA have been reported to stimulate osteoblastic differentiation and inhibit osteoclast formation in vitro. However, it is unclear if they are the bioactive ingredients that account for the in vivo actions of FLL on Ca balance and bone properties. The present study was designed to study if OA or OA+UA mimicked the effects of FLL on bone and calcium homeostasis using ovariectomized (OVX) rats. Three‐month‐old female Sprague Dawley rats were subjected to ovariectomy and after a two‐month stabilization period, were randomly assigned to 4 groups (n =13/group) fed with experimental diet containing FLL (700mg/kg/d), OA (25mg/kg/d), or OA (25mg/kg/d) + UA (8.3mg/kg/d) or control diet for 6 weeks. All diets contained 0.6% Ca, 0.65% P. Ca balance was measured in rats at week 1 and 6 and Ca kinetic study was performed at week 6 with 45Ca tracer. Calcium kinetics were modeled using WinSAAM software and a 3‐compartment model. At sacrifice, left femur and lumbar vertebra were collected for micro‐CT scanning and serum was obtained for 1,25(OH)2D3 measurement using a commercial kit. FLL, OA, and OA+UA diets significantly improved bone mineral density, bone volume to total volume, and trabecular thickness in femurs in OVX rats. Ca balance, however, was not altered in response to diet treatment at either week 1 or week 6 in OVX rats. As predicted by kinetic modeling, rats fed with OA and OA+UA diets deposited more calcium in bone and resorbed more calcium from the skeleton while rats fed with FLL and OA+UA diets decreased endogenous excretion of calcium as compared to those fed the control diet. All three treatments resulted in a higher mass of compartment 3 (vs. control group) due to changes of transfer rate between compartment 2 and 3, and appeared to be associated with their effects on increasing serum 1,25(OH)2D3 level in OVX rats. In summary, OA and OA+UA mimicked the effects of FLL on improving calcium utilization, protecting bone and modulating serum 1,25(OH)2D3 level in OVX rats, indicating that OA and UA are the bioactive ingredients that account for the in vivo actions of FLL.Support or Funding InformationThe study was supported by research fund (15100015) and research studentship for Miss Si Si Cao from the Hong Kong Polytechnic University as well as funding from National Science Foundation, PR China (81528024).
The effects of iron status on testosterone biosynthesis and testicular antioxidant capacity in male rats
Authors: Tsao Chih‐Wei , Liao Yuan‐Ru , Liew Yih‐Fong , Lin Ying‐Hung , Hsu Yu‐Juei , Liu Chin‐yu 
Published: November 2023

Iron is an essential element for almost all living organisms as it participates in a wide variety of metabolic processes, including oxygen transport, deoxyribonucleic acid (DNA) synthesis, and electron transport. Previous study found that iron deficiency may lead to decreasing spermatozoa vitality, DNA damage, and oxidative stress. However, few studies did describe the relationships between the iron deficiency and testicular functions were not well‐known. The aim of this study is to explore the association between iron deficiency and hypogonadism. Thirty‐two weaning male Wistar rats were divided into iron‐adequate control group (AI), moderate iron‐deficient group (MID), severe iron‐deficient group (ID) and severe iron‐deficient pair‐fed group (IPF). The rats are fed the diet with different content of iron for four weeks and then sacrificed after fasting for 12 hours. Iron deficiency caused a significant reduction in serum testosterone, 3β‐hydroxysteroid dehydrogenase (3β‐HSD) and CYP11A1 protein. The expression of Bax/Bcl2 and c‐PARP were induced in the ID group. The hematoxylin‐eosin staining of ID group that the diminished seminiferous tubule sizes and degenerated germinal cells was observed. In addition, SOD (superoxide dismutase) level in testis tissues was also decreased in the ID group. Iron deficiency may lead to reduction of testosterone biosynthesis due to induction the oxidative stress and apoptosis in the testis tissue.Support or Funding InformationMOST 104‐2314‐B‐016‐029, Ministry of Science and Technology, Taiwan