Journal of Nutrition最新文献

{"title":"Obesity and Gut Health: Link for the Future. Could Kombucha Be Our Ally?","authors":"Roberto Cannataro","doi":"10.1016/j.tjnut.2025.02.016","DOIUrl":"10.1016/j.tjnut.2025.02.016","url":null,"abstract":"","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oleuropein Supplementation Increases Resting Skeletal Muscle Fractional Pyruvate Dehydrogenase Activity but Does Not Influence Whole-Body Metabolism: A Randomized, Double-Blind, and Placebo-Controlled Trial in Healthy, Older Males.","authors":"Philippe Jm Pinckaers, Heather L Petrick, Astrid Mh Horstman, Alba Moreno-Asso, Umberto De Marchi, Floris K Hendriks, Lisa Me Kuin, Cas J Fuchs, Dominik Grathwohl, Lex B Verdijk, Antoine H Zorenc, Joan Mg Senden, Eugenia Migliavacca, Sylviane Metairon, Laure Poquet, Delphine Morin-Rivron, Leonidas G Karagounis, Graham P Holloway, Jerome N Feige, Luc Jc van Loon","doi":"10.1016/j.tjnut.2025.02.015","DOIUrl":"10.1016/j.tjnut.2025.02.015","url":null,"abstract":"<p><strong>Background: </strong>The polyphenol oleuropein activates mitochondrial calcium import, which increases pyruvate dehydrogenase (PDH) activity. Preclinically, this increase in PDH activity following oleuropein supplementation resulted in improved mitochondrial bioenergetics and fatigue resistance.</p><p><strong>Objectives: </strong>This study aimed to examine the effects of acute and chronic oleuropein supplementation on muscle energy metabolism, whole-body substrate metabolism, strength, and fatigue resistance in older males.</p><p><strong>Methods: </strong>In a randomized, double-blind, placebo-controlled trial, 40 healthy older males (60 ± 5y) received either placebo (PLA) or 100 mg oleuropein from 250 mg olive leaf extract (OLE) supplementation daily for 36 d. On day 1 and day 36, muscle and blood samples were collected, and indirect calorimetry was performed before and ≤120 min following supplement intake. Leg strength and fatigue were measured before and after 29 d of supplementation. Results were analyzed using analysis of covariance or robust analysis of covariance.</p><p><strong>Results: </strong>OLE ingestion on day 1 and day 36 increased plasma oleuropein metabolites (P < 0.001). On day 1, no differences were observed in muscle PDH activity, mitochondrial respiration, or whole-body substrate metabolism 120 min after acute OLE ingestion. Ribonucleic acid sequencing revealed upregulation of oxidative phosphorylation gene pathways (false discovery rate < 0.05), whereas PDH-Ser²⁹³-phosphorylation was higher after acute OLE compared with PLA ingestion (P = 0.015). Following chronic supplementation, fractional PDH activity was ∼25% greater in OLE compared with PLA (49 ± 14 compared with 38 ± 10%; P = 0.016) with no differences in absolute PDH activity and PDH-Ser²⁹³-phosphorylation between groups. Mitochondrial respiration and protein content, whole-body substrate metabolism, leg strength, and fatigue resistance were not different between OLE and PLA. Plasma low-density lipoprotein cholesterol was lower after chronic OLE compared with PLA (P = 0.043), with no differences in other blood metabolic markers.</p><p><strong>Conclusions: </strong>Chronic OLE supplementation resulted in higher skeletal muscle fractional PDH activity in healthy, older males, which may impact resting energy metabolism. Acute or chronic oleuropein supplementation does not modulate skeletal muscle mitochondrial respiration, muscle strength, muscle fatigue, or whole-body substrate metabolism. This trial was registered at clinicaltrials.gov as NCT05217433.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Necroptosis, Pyroptosis, and Ferroptosis in Porcine Intestinal Injury and Their Regulation by Nutrients and Bioactive Substances.","authors":"Kan Xiao, Bei Zhou, Yulan Liu","doi":"10.1016/j.tjnut.2025.02.020","DOIUrl":"10.1016/j.tjnut.2025.02.020","url":null,"abstract":"<p><p>In the early stages of development, piglets exhibit immature intestinal morphology and function, rendering them susceptible to a range of internal and external stressors, such as viral and bacterial infection, and mycotoxin exposure, which causes intestinal damage. The intestinal damage is characterized by various types of cell death within intestinal epithelium. The traditional cell death types have been categorized as necrosis, apoptosis, and autophagy. However, recent research has identified several forms of novel regulated cell death (RCD) such as necroptosis, pyroptosis, and ferroptosis. A growing body of evidence has underscored the pivotal role of necroptosis, pyroptosis, and ferroptosis in intestinal damage in pigs. Moreover, intervention strategies have been shown to mitigate these 3 RCDs when pigs are exposed to excessive adverse factors. This review aims to elucidate the role of these emerging RCDs in intestinal damage and summarize current understanding of their regulation by nutrients and bioactive substances in pigs. Our goal was to provide future intervention strategies designed to alleviate intestinal damage in pigs.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Potential Toxicity of Bread Fortification With Vitamin D in General Population: A Predictive Modeling Study.","authors":"Bahareh Nikooyeh, Michael F Holick, Zahra Abdollahi, Hamid Rasekhi, Maryam Amini, Delaram Ghodsi, Zahra Yari, Samira Rabiei, Ali Kalayi, Maliheh Zahedirad, Hootan Yazdani, Marjan Rismanchi, Tirang R Neyestani","doi":"10.1016/j.tjnut.2025.02.019","DOIUrl":"10.1016/j.tjnut.2025.02.019","url":null,"abstract":"<p><strong>Background: </strong>Vitamin D fortification of bakery's wheat flour, which excludes flours used for confectionaries and bulky breads, can be a suitable strategy to improve vitamin D status of the general population.</p><p><strong>Objectives: </strong>This study aimed to generate a predictive model to anticipate the effectiveness and potential risk of vitamin D-fortified bread in different fortification doses in general population.</p><p><strong>Methods: </strong>To gather baseline data before implementation of flour fortification, a cross-sectional descriptive study was conducted on a representative sample comprising 1051 subjects aged 7-65 y from 2 cities Birjand and Yazd. Demographic, anthropometric, and laboratory assessments were performed for all subjects. The amount of bread consumption was estimated using a 24-h recall questionnaire. A simulation model was used to examine the impact of various fortification doses of vitamin D in bread on the proportion of both adults and children achieving sufficient circulating 25-hydroxycalciferol [25(OH)D] concentrations (>50 nmol/L) and potential harm thresholds (>375 nmol/L). The baseline serum 25(OH)D concentration data were used as a reference for comparison at each fortification dose. Circulating 25(OH)D between 27.5 and 50 nmol/L and below 27.5 nmol/L was considered as insufficiency and deficiency, respectively.</p><p><strong>Results: </strong>Substantial proportions of both children and adults fell into the insufficient (37.5% and 37.4%, respectively) and deficient (34.7% and 31.8%, respectively) categories. Our model showed that the fortification dose of 250 IU/100g bread could be an effective strategy for significantly improving vitamin D status in the general population. Higher doses, such as 500 IU/100g, results in >70% of the population achieving sufficient 25(OH)D concentrations. However, starting at 400 IU/100 g bread, a very small percentage (0.1%) of the population could reach potentially harmful concentrations.</p><p><strong>Conclusions: </strong>By adding 250-350 IU vitamin D per 100 g bread, over half of the general population can reach to sufficient vitamin D status with no potential risk of toxicity.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium and Phosphorus Retention and Excretion in Different Strains of Laying Hens during Brooding Period and Key Genes Regulating Calcium and Phosphate Transport.","authors":"Ruochen Yang, Bowen Lu, Tengchuan Li, Zhonghao Liu, Lihong Zhao, Shimeng Huang, Qiugang Ma","doi":"10.1016/j.tjnut.2025.02.018","DOIUrl":"10.1016/j.tjnut.2025.02.018","url":null,"abstract":"<p><strong>Background: </strong>Calcium (Ca) and phosphorus (P) intake during brooding affects laying hens' later production and health, with availability varying among strains, necessitating further investigation of the factors influencing these differences.</p><p><strong>Objectives: </strong>This study aimed to compare the availability of Ca and P and related gene expression among 3 high-yielding layer strains during the first 6 wk and identify genes strongly associated with nutrient absorption.</p><p><strong>Methods: </strong>Ninety pullets (1-d-old, female) from 3 strains [medium size, large egg layer (ML), light size, medium egg layer (LM), and dwarf, small egg layer (DS) weighted 31.533 ± 0.63 g, 39.367 ± 1.40 g, and 34.099 ± 0.64 g, respectively] were randomly assigned to 6 replicates of 15 birds each for 6-wk cage rearing. Feces were collected weekly to track the Ca and P availability. Initial and final body weights and tibial lengths were recorded to determine growth performance. Intestinal samples were collected to determine the gene expression of Ca and P transporters [transient receptor potential cation channel subfamily V member 6, calbindin D28k, Na+/Ca2+ exchanger 1 (NCX1), plasma membrane Ca-ATPase 1b, and sodium-dependent phosphate transporter IIb (NPt2b)] as well as tight junction proteins (claudin-2 and claudin-12).</p><p><strong>Results: </strong>ML and LM pullets exhibited significantly greater body weight (443 g, 436 g compared with 319 g, P < 0.001) and tibial length (70.6 mm, 69.6 mm compared with 59.2 mm, P < 0.001) than DS. Notably, during the sixth week, the Ca and P retention in DS (0.847 g/wk compared with 1.648 g/wk, 0.662 g/wk compared with 1.141 g/wk) was significantly lower than that in ML, and in most weeks, DS exhibited the lowest Ca availability among the 3 strains. Gene expression analysis revealed higher expression levels of Ca transporters in the duodenum of ML and LM than in DS, whereas DS demonstrated elevated transporter expression in the jejunum. Furthermore, ML and LM exhibited more pronounced expression of tight junction proteins across most intestinal segments.</p><p><strong>Conclusions: </strong>The study indicated that expression of Ca and P transporter is highest in the duodenum, and duodenal NCX1, NPt2b were the genes most significantly positively correlated with the retention and excretion of Ca and P in pullets.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Honokiol, a Neolignan from Magnolia officinalis, Attenuated Fructose-Induced Hepatic Fat Accumulation by Improving Intestinal Barrier Function in Mice.","authors":"Anja Baumann, Verena Freutsmiedl, Julia Jelleschitz, Raphaela Staltner, Annette Brandt, Daniel Schachner, Verena M Dirsch, Ina Bergheim","doi":"10.1016/j.tjnut.2025.02.017","DOIUrl":"10.1016/j.tjnut.2025.02.017","url":null,"abstract":"<p><strong>Background: </strong>Fructose (Fru) consumption has been suggested to contribute to metabolic diseases including metabolic dysfunction-associated steatotic liver disease (MASLD), at least in part, by disturbing intestinal barrier function and intestinal nitric oxide (NO) homeostasis. Honokiol (Hon), a neolignan found in Magnolia officinalis, has been suggested to affect intestinal integrity and barrier function.</p><p><strong>Objectives: </strong>We assessed whether Hon affects Fru-induced small intestinal permeability in settings of early MASLD.</p><p><strong>Methods: </strong>Female 8-10-wk-old C57BL/6J mice (n = 7/group) received either a 30% Fru solution + vehicle or plain drinking water + vehicle ± Hon (10 mg/kg bw/d) for 4 wk. Liver damage [e.g. nonalcoholic fatty liver disease activity score (NAS), number of neutrophils, interleukin-6 (IL-6) protein concentration], markers of intestinal permeability (bacterial endotoxin, tight junction proteins), and NO homeostasis in the small intestine were determined in vivo as well as ex vivo in an everted sac model and in Caco-2 cells. One-way and 2-way analysis of variance were performed, respectively.</p><p><strong>Results: </strong>Hon diminished the development of MASLD, which was associated with a significant lower NAS (-38%), number of neutrophils (-48%), and IL-6 protein concentrations (-38%) in livers of Fru-fed mice. Hon also attenuated Fru-induced alterations of markers of intestinal barrier function with Fru+Hon-fed mice showing lower bacterial toxin levels in portal plasma (-29%, P = 0.075), higher tight junction protein concentrations (+2.4-fold, P < 0.05), and lower NOx concentration (-44%, P < 0.05) as well as NO synthase activity (-35%) in the small intestine compared with Fru+vehicle-fed mice. Moreover, the decrease in AMP-activated protein kinase phosphorylation found in the small intestine of Fru-fed mice was significantly attenuated (+5.3-fold) by the concomitant treatment with Hon in Fru-fed mice. In support of the in vivo findings, Hon significantly attenuated Fru-induced intestinal permeability ex vivo and in Caco-2 cells.</p><p><strong>Conclusions: </strong>Our data suggest that Hon diminished the development of Fru-induced early MASLD by alleviating impairments in intestinal barrier function.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Restated and More Straightforward Retinol Isotope Dilution Equation for Predicting Vitamin A Total Body Stores.","authors":"Michael H Green, Joanne Balmer Green","doi":"10.1016/j.tjnut.2025.01.036","DOIUrl":"10.1016/j.tjnut.2025.01.036","url":null,"abstract":"","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Short-Chain Fatty Acids Supplementation Improves Reproductive Performance and Gut Microbiota in Gilts.","authors":"Baoyang Xu, Wenxia Qin, Yuwen Chen, Juncheng Huang, Libao Ma, Xianghua Yan","doi":"10.1016/j.tjnut.2025.02.012","DOIUrl":"10.1016/j.tjnut.2025.02.012","url":null,"abstract":"<p><strong>Background: </strong>Short-chain fatty acids (SCFAs) have emerged as critical modulators of female reproductive function and host gut microbiota.</p><p><strong>Objectives: </strong>This study aimed to investigate the impact of dietary SCFAs supplementation on reproductive performance and gut microbiota in gilts, and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>Eighty gilts (95 d old) were randomly assigned to either a control group (Ctrl, 40 gilts) receiving a basal diet, or a SCFAs treatment group (SCFAs, 40 gilts) receiving a basal diet supplemented with 0.13% sodium acetate, 0.11% sodium propionate, and 0.09% sodium butyrate. At third estrus, 13 gilts (6 from Ctrl and 7 from SCFAs) were killed for follicular development and gut microbiota analysis, whereas the remaining gilts completed gestation for reproductive performance assessment.</p><p><strong>Results: </strong>SCFAs group had higher total number born (11.97 compared with 9.44) and total number born alive (11.28 compared with 9.34) compared with Ctrl group (P < 0.05). SCFAs group had increased counts of secondary follicles (36.14 compared with 26.83), antral follicles (10.29 compared with 6.67), and corpus luteum (25.09 compared with 19.33), alongside had reduced atretic follicles (15.32 compared with 20.67) compared with Ctrl group (P < 0.05). Proteomic analysis revealed that SCFAs-induced differentially expressed proteins (DEPs) were significantly enriched in the follicular development-related pathways (P < 0.05). Apoptosis-related DEPs positively correlated with follicular development indices (P < 0.05), consistent with the reduced apoptosis observed in ovarian granulosa cells of the SCFAs group. Additionally, SCFAs supplementation improved both the composition and alpha-diversity (P < 0.05) of gilts' gut microbiota. Furthermore, both the SCFAs-enriched bacteria and plasma SCFAs concentrations showed positive associations with gilts' follicular development indices (P < 0.05).</p><p><strong>Conclusions: </strong>Dietary SCFAs supplementation enhances reproductive performance in gilts by promoting ovarian follicular maturation and optimizing gut microbiota composition.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The STRIPED Dietary Supplement Label Explorer: A Tool to Identify Supplements Sold with Weight-Loss, Muscle-Building, and Cleanse/Detox Claims.","authors":"Julia A Vitagliano, Jill R Kavanaugh, Boone Gorges, Xiaokang Fu, Kieran Todd, Carly E Milliren, Amanda Raffoul, S Bryn Austin","doi":"10.1016/j.tjnut.2025.02.007","DOIUrl":"10.1016/j.tjnut.2025.02.007","url":null,"abstract":"<p><strong>Background: </strong>Limited federal premarket oversight over United States-sold dietary supplements impedes consumer safety and product efficacy. The Dietary Supplement Label Database (DSLD) was created to increase publicly available information on United States-sold dietary supplements. Building on what the DSLD was designed to provide, we aimed to create a comprehensive database that can facilitate searches on supplements sold with weight loss, muscle building, and cleanse/detox claims, supplement categories previously flagged for misleading claims and containing toxic ingredients.</p><p><strong>Objectives: </strong>This study aims to leverage publicly available DSLD Application Programming Interface (API) to develop an easy-to-use tool to classify DSLD supplement labels with weight loss, muscle building and cleanse/detox claims.</p><p><strong>Methods: </strong>A 4-step categorization methodology was used to develop the tool: 1) create reference standard database by deductively coding claims (weight loss, muscle building, and cleanse/detox) on 5000 DSLD labels; 2) develop 3 systematic heuristics (1 per claim) and refine heuristics as assessed by recall, specificity, precision, negative predictive value, F1 Score, and accuracy; 3) develop multimodal deep learning model as an additional method to identify the 3 claims; and 4) compare models' performance using the receiver operating characteristic (ROC) curve and efficiency analyses (i.e. hours of human labor taken to develop each model).</p><p><strong>Results: </strong>Of the 4745 DSLD labels included in the reference standard database, 4.2% were defined using the criteria as weight loss, 6.3% muscle building, and 3.0% cleanse/detox. Three systematic heuristics for each claim were refined 4 times, with pass 4 exceeding prior passes' performances. ROC curve analyses indicated that systematic heuristic performed significantly better (P < 0.05) than the multimodal deep learning model at classifying cleanse/detox labels, yet efficiency analyses found systematic heuristics less efficient (110 compared with 30 h).</p><p><strong>Conclusions: </strong>Our findings illustrate the feasibility of using the DSLD API to create a tool that classifies weight loss, muscle building, and cleanse/detox labels using our supplement label categorization methodology. This publicly available tool, STRIPED Dietary Supplement Label Explorer, may be used to support future research and the monitoring of claims on dietary supplement labels.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol Reprograms Placental Glucose and Lipid Metabolism, Which Correlate with Reduced Fetal Brain but not Body Weight in a Mouse Model of Prenatal Alcohol Exposure.","authors":"Nipun Saini, Sandra M Mooney, Susan M Smith","doi":"10.1016/j.tjnut.2025.02.011","DOIUrl":"10.1016/j.tjnut.2025.02.011","url":null,"abstract":"<p><strong>Background: </strong>Prenatal alcohol exposure (PAE) impairs fetal growth and brain development. Dysregulated placental function contributes to these deficits. Whether PAE also disrupts its metabolic functions to impede fetal development is unclear.</p><p><strong>Objectives: </strong>We performed untargeted metabolomics to gain mechanistic insights on how PAE impacts placental metabolism and fetal nutrient availability.</p><p><strong>Methods: </strong>Pregnant C57BL/6J mice were gavaged with alcohol (ALC, 3 g/kg) or isocaloric maltodextrin (CON) daily on embryonic days (E) E8.5 through E17.5. We performed untargeted metabolomics on placentas harvested at E17.5.</p><p><strong>Results: </strong>Alcohol reduced placental glucose and glycolytic intermediates and increased tricarboxylic acid (TCA) cycle intermediates, suggesting a shift from glucose to lipids to meet its high energetic demands. This was complemented by elevations in intermediates of the pentose phosphate and glucosamine pathways, indicating a diversion of glucose into nonoxidative fates. Alcohol also decreased aspartate and asparagine, consistent with the limited glucose availability and increased fetal demand for nitrogen acceptors to support its increased gluconeogenesis and urea production. Alcohol also caused a selective increase in purine metabolites despite the limited availability of donor sources glucose, serine, glycine, glutamine, and asparagine. Uridine nucleotides were also elevated and may represent an adaptive change to meet the increased need for thiamin pyrophosphate in the oxidative decarboxylations of the TCA cycle and pentose phosphate pathways. Decreases in multiple oxylipins having antivasoconstriction actions could be a mechanism by which alcohol alters the placental vasculature and promotes vasoconstriction. Importantly, the selective and strong correlation of these dysregulated metabolites with reduced fetal brain weight, but not body weight, affirms the importance of the placenta-brain axis and placental metabolism on brain development.</p><p><strong>Conclusions: </strong>Alcohol causes metabolic dysregulation and reprogramming of the late-term placenta. These changes limit fetal nutrient availability and contribute to the reduced brain development and cognitive impairments that partly typify PAE.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}