Microbiota-host crosstalk has an important role in maintaining metabolic homeostasis and regulating reproductive endocrine functions. However, the effects of maternal microbiota in reproduction and their underlying mechanisms have not been fully understood. In this study, we systematically reviewed the regulation of maternal microbiota on maintaining steroid hormone synthesis, relieving reproductive organ disorders, and improving follicular and fetal development. Moreover, the molecular mechanisms including the nutritional modulation of maternal microbiota on pregnancy outcomes and offspring growth were also discussed. In summary, maternal microbiota contributes to reproductive organs health and embryonic and fetal development, leading to profound impacts on offspring growth. These insights provide new opportunities to develop strategies aimed at optimizing maternal microbiomes to improve reproductive performance in mammals.
{"title":"Maternal Microbiota and Its Potential Implications for Mammalian Reproduction Health.","authors":"Xinyu Lei, Yulian Zheng, Yuwen Chen, Jiayan Jiang, Guoxun Chen, Qianhong Ye","doi":"10.1016/j.tjnut.2026.101366","DOIUrl":"10.1016/j.tjnut.2026.101366","url":null,"abstract":"<p><p>Microbiota-host crosstalk has an important role in maintaining metabolic homeostasis and regulating reproductive endocrine functions. However, the effects of maternal microbiota in reproduction and their underlying mechanisms have not been fully understood. In this study, we systematically reviewed the regulation of maternal microbiota on maintaining steroid hormone synthesis, relieving reproductive organ disorders, and improving follicular and fetal development. Moreover, the molecular mechanisms including the nutritional modulation of maternal microbiota on pregnancy outcomes and offspring growth were also discussed. In summary, maternal microbiota contributes to reproductive organs health and embryonic and fetal development, leading to profound impacts on offspring growth. These insights provide new opportunities to develop strategies aimed at optimizing maternal microbiomes to improve reproductive performance in mammals.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":"101366"},"PeriodicalIF":3.8,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998350","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}
Pub Date : 2026-01-14DOI: 10.1016/j.tjnut.2026.101365
Melissa C Kay , Andrew Fansler , Brenda Sun , Deepak Palakshappa , Kimberly Montez , Callie L Brown , Christine Borger
Background
Food insecurity remains a significant public health concern in the United States, disproportionately affecting households with young children and posing risks to both nutritional status and developmental outcomes.
Objectives
This study investigates how the duration and frequency of food insecurity affect diet quality and developmental outcomes in preschool children aged 2–5 y, using data from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Infant and Toddler Feeding Practices Study-2.
Methods
Households were categorized by frequency of food insecurity: persistent (at all time points), frequent (at several), rare (at few), and never. Bivariate analyses examined the relationship between food insecurity frequency and both Healthy Eating Index (HEI)-2020 scores and Ages & Stages Questionnaires-3 responses. Multivariable linear and logistic regressions assessed associations between food insecurity and child outcomes, with statistical weights applied to represent the eligible WIC population.
Results
Among 981 participants, persistent food insecurity declined from 16.4% (aged 2–3 y) to 9.8% (aged 2–5 y), whereas households never experiencing food insecurity dropped from 62.9% to 55.8%. Children in persistently food insecure households had significantly lower HEI-2020 scores at age 3 (P = 0.014) compared with those in food-secure households. In addition, persistent food insecurity was linked with lower odds of typical developmental outcomes at ages 3.5 [odds ratio (OR): 0.49; confidence interval (CI): 0.30, 0.79] and 4.5 (OR: 0.35; CI: 0.16, 0.73) years.
Conclusions
The findings indicate that persistent food insecurity is associated with poorer diet quality at age 3 y and negative developmental outcomes at ages 3.5 and 4.5 y. Future research should continue to explore the long-term impacts of food insecurity, considering a broader range of contextual factors to clarify mechanisms and identify effective intervention points.
{"title":"Duration of Food Insecurity and Childhood Diet and Development: Special Supplemental Nutrition Assistance Program for Women, Infants, and Children Infant and Toddler Feeding Practices Study-2 Findings","authors":"Melissa C Kay , Andrew Fansler , Brenda Sun , Deepak Palakshappa , Kimberly Montez , Callie L Brown , Christine Borger","doi":"10.1016/j.tjnut.2026.101365","DOIUrl":"10.1016/j.tjnut.2026.101365","url":null,"abstract":"<div><h3>Background</h3><div>Food insecurity remains a significant public health concern in the United States, disproportionately affecting households with young children and posing risks to both nutritional status and developmental outcomes.</div></div><div><h3>Objectives</h3><div>This study investigates how the duration and frequency of food insecurity affect diet quality and developmental outcomes in preschool children aged 2–5 y, using data from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Infant and Toddler Feeding Practices Study-2.</div></div><div><h3>Methods</h3><div>Households were categorized by frequency of food insecurity: persistent (at all time points), frequent (at several), rare (at few), and never. Bivariate analyses examined the relationship between food insecurity frequency and both Healthy Eating Index (HEI)-2020 scores and Ages & Stages Questionnaires-3 responses. Multivariable linear and logistic regressions assessed associations between food insecurity and child outcomes, with statistical weights applied to represent the eligible WIC population.</div></div><div><h3>Results</h3><div>Among 981 participants, persistent food insecurity declined from 16.4% (aged 2–3 y) to 9.8% (aged 2–5 y), whereas households never experiencing food insecurity dropped from 62.9% to 55.8%. Children in persistently food insecure households had significantly lower HEI-2020 scores at age 3 (<em>P</em> = 0.014) compared with those in food-secure households. In addition, persistent food insecurity was linked with lower odds of typical developmental outcomes at ages 3.5 [odds ratio (OR): 0.49; confidence interval (CI): 0.30, 0.79] and 4.5 (OR: 0.35; CI: 0.16, 0.73) years.</div></div><div><h3>Conclusions</h3><div>The findings indicate that persistent food insecurity is associated with poorer diet quality at age 3 y and negative developmental outcomes at ages 3.5 and 4.5 y. Future research should continue to explore the long-term impacts of food insecurity, considering a broader range of contextual factors to clarify mechanisms and identify effective intervention points.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 3","pages":"Article 101365"},"PeriodicalIF":3.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989681","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}
Pub Date : 2026-01-13DOI: 10.1016/j.tjnut.2026.101364
Lauren T Berube , Chan Wang , Margaret Curran , Mary Lou Pompeii , Lu Hu , Souptik Barua , Huilin Li , David E St-Jules , Antoinette Schoenthaler , Eran Segal , Michael Bergman , Collin J Popp
Background
Dietary self-monitoring is central to effective personalized nutrition, providing critical data to inform tailored feedback and support behavior change.
Objectives
To examine the impact of dietary self-monitoring adherence and the indirect effect of personalized scores to predict postprandial glycemic response (PPGR) on weight loss.
Methods
Post hoc analysis of the Personal Diet Study that investigated the impact of a machine algorithm-based diet that integrates clinical and microbiome features (Personalized) compared with a standard, low-fat diet (Standardized) on weight loss. All participants received behavioral counseling and were encouraged to self-monitor dietary intake via a smartphone application. Personalized received algorithm-based scores (1–5) on predicted PPGR to foods logged (PPGR score; 1–2 indicating optimal; 3–5 suboptimal). Dietary self-monitoring adherence was the percentage of days logging ≥50% of target calories, classified as high or low. PPGR score quality was calculated by the proportion of optimal predicted PPGR scores per day; defined as “high-PPGR quality” days when this exceeded the group average. Mediation analysis assessed whether PPGR quality mediated the relationship between dietary self-monitoring adherence and weight loss.
Results
Participants with high self-monitoring adherence lost an average of 4.2% of their baseline weight, compared with 1.9% among those with low adherence (P = 0.016). High self-monitoring adherence was associated with a greater likelihood of achieving ≥5% weight loss (adjusted odds ratio: 3.67; 95% confidence interval: 1.63, 8.50). Within Personalized, high-PPGR quality mediated 53.4% of the total effect of self-monitoring adherence on weight loss (P < 0.001).
Conclusion
Consistent self-monitoring coupled with personalized feedback may significantly enhance weight loss in a precision nutrition approach.
This trial was registered at https://clinicaltrials.gov/ as NCT03336411.
{"title":"Personalized Dietary Feedback Mediates the Association of Dietary Self-Monitoring Adherence and Weight Loss: A Post Hoc Analysis of the Personal Diet Study","authors":"Lauren T Berube , Chan Wang , Margaret Curran , Mary Lou Pompeii , Lu Hu , Souptik Barua , Huilin Li , David E St-Jules , Antoinette Schoenthaler , Eran Segal , Michael Bergman , Collin J Popp","doi":"10.1016/j.tjnut.2026.101364","DOIUrl":"10.1016/j.tjnut.2026.101364","url":null,"abstract":"<div><h3>Background</h3><div>Dietary self-monitoring is central to effective personalized nutrition, providing critical data to inform tailored feedback and support behavior change.</div></div><div><h3>Objectives</h3><div>To examine the impact of dietary self-monitoring adherence and the indirect effect of personalized scores to predict postprandial glycemic response (PPGR) on weight loss.</div></div><div><h3>Methods</h3><div>Post hoc analysis of the Personal Diet Study that investigated the impact of a machine algorithm-based diet that integrates clinical and microbiome features (Personalized) compared with a standard, low-fat diet (Standardized) on weight loss. All participants received behavioral counseling and were encouraged to self-monitor dietary intake via a smartphone application. Personalized received algorithm-based scores (1–5) on predicted PPGR to foods logged (PPGR score; 1–2 indicating optimal; 3–5 suboptimal). Dietary self-monitoring adherence was the percentage of days logging ≥50% of target calories, classified as high or low. PPGR score quality was calculated by the proportion of optimal predicted PPGR scores per day; defined as “high-PPGR quality” days when this exceeded the group average. Mediation analysis assessed whether PPGR quality mediated the relationship between dietary self-monitoring adherence and weight loss.</div></div><div><h3>Results</h3><div>Participants with high self-monitoring adherence lost an average of 4.2% of their baseline weight, compared with 1.9% among those with low adherence (<em>P</em> = 0.016). High self-monitoring adherence was associated with a greater likelihood of achieving ≥5% weight loss (adjusted odds ratio: 3.67; 95% confidence interval: 1.63, 8.50). Within Personalized, high-PPGR quality mediated 53.4% of the total effect of self-monitoring adherence on weight loss (<em>P</em> < 0.001).</div></div><div><h3>Conclusion</h3><div>Consistent self-monitoring coupled with personalized feedback may significantly enhance weight loss in a precision nutrition approach.</div><div>This trial was registered at <span><span>https://clinicaltrials.gov/</span><svg><path></path></svg></span> as NCT03336411.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 3","pages":"Article 101364"},"PeriodicalIF":3.8,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989671","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}
Pub Date : 2026-01-13DOI: 10.1016/j.tjnut.2026.101363
Joyeta Ghosh , Tinni Chaudhuri , Jose Arturo Molina Mora , Jyoti Taneja , Ravi Kant
Background
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among postmenopausal women in rural India, where healthcare resources remain limited.
Objectives
This study aimed to leverage artificial intelligence (AI) and machine learning (ML) approaches to predict CVD risk in rural elderly women, identify key clinical predictors, and assess model performance using interpretable AI tools.
Methods
This observational cross-sectional study was conducted in Singur Block (West Bengal) and Amdanga Block (North 24 Parganas District) between March 2014 and August 2018. Data from 458 rural postmenopausal women were analyzed. The outcome variable was the presence or absence of elevated cardiovascular disease risk, defined using composite International Diabetes Federation and American Heart Association criteria. Predictors included waist circumference, blood pressure, fasting blood glucose, HDL cholesterol, triglycerides, and vitamin D concentrations. Seven ML models [Random Forest, Gradient Boosting, Ensemble (Voting Classifier), Extra Trees, Support Vector Machine, Neural Network, and Logistic Regression] were developed and compared. Model evaluation employed 5-fold cross-validation with metrics including accuracy, AUC, precision, recall, and F1 score.
Results
Among the 458 participants, 171 (37.3%) exhibited elevated CVD risk. The Random Forest model achieved an accuracy of 98.91% (95% CI: 97.8%, 99.6%), whereas eXtreme Gradient Boosting (XGBoost) demonstrated comparable performance with an AUC of 0.998 (95% CI: 0.993, 1.000), precision of 97.2%, and recall of 98.3%. Feature-importance analysis revealed waist circumference, blood pressure, and fasting glucose as the strongest predictors, with HDL cholesterol and vitamin D contributing modestly but significantly.
Conclusions
ML models—particularly Random Forest and XGBoost—demonstrated high accuracy and interpretability in predicting CVD risk among rural postmenopausal women. These findings highlight the potential of AI-driven, low-cost predictive tools for early CVD risk detection and personalized preventive healthcare in resource-limited rural settings.
{"title":"Harnessing Clinical and Biochemical Data for Personalized Cardiovascular Risk Prediction: a Machine Learning Approach Toward Precision Nutrition","authors":"Joyeta Ghosh , Tinni Chaudhuri , Jose Arturo Molina Mora , Jyoti Taneja , Ravi Kant","doi":"10.1016/j.tjnut.2026.101363","DOIUrl":"10.1016/j.tjnut.2026.101363","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among postmenopausal women in rural India, where healthcare resources remain limited.</div></div><div><h3>Objectives</h3><div>This study aimed to leverage artificial intelligence (AI) and machine learning (ML) approaches to predict CVD risk in rural elderly women, identify key clinical predictors, and assess model performance using interpretable AI tools.</div></div><div><h3>Methods</h3><div>This observational cross-sectional study was conducted in Singur Block (West Bengal) and Amdanga Block (North 24 Parganas District) between March 2014 and August 2018. Data from 458 rural postmenopausal women were analyzed. The outcome variable was the presence or absence of elevated cardiovascular disease risk, defined using composite International Diabetes Federation and American Heart Association criteria. Predictors included waist circumference, blood pressure, fasting blood glucose, HDL cholesterol, triglycerides, and vitamin D concentrations. Seven ML models [Random Forest, Gradient Boosting, Ensemble (Voting Classifier), Extra Trees, Support Vector Machine, Neural Network, and Logistic Regression] were developed and compared. Model evaluation employed 5-fold cross-validation with metrics including accuracy, AUC, precision, recall, and F1 score.</div></div><div><h3>Results</h3><div>Among the 458 participants, 171 (37.3%) exhibited elevated CVD risk. The Random Forest model achieved an accuracy of 98.91% (95% CI: 97.8%, 99.6%), whereas eXtreme Gradient Boosting (XGBoost) demonstrated comparable performance with an AUC of 0.998 (95% CI: 0.993, 1.000), precision of 97.2%, and recall of 98.3%. Feature-importance analysis revealed waist circumference, blood pressure, and fasting glucose as the strongest predictors, with HDL cholesterol and vitamin D contributing modestly but significantly.</div></div><div><h3>Conclusions</h3><div>ML models—particularly Random Forest and XGBoost—demonstrated high accuracy and interpretability in predicting CVD risk among rural postmenopausal women. These findings highlight the potential of AI-driven, low-cost predictive tools for early CVD risk detection and personalized preventive healthcare in resource-limited rural settings.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 3","pages":"Article 101363"},"PeriodicalIF":3.8,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989710","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}
Metformin, a first-line pharmacologic agent for type 2 diabetes, exerts its primary antidiabetic effects by suppressing hepatic gluconeogenesis via both AMP-activated protein kinases-dependent and -independent pathways. Beyond glycemic control, metformin exhibits pleiotropic benefits, including improved insulin sensitivity, modulation of gut microbiota, and protection against various metabolic, cardiovascular, renal, neurodegenerative, and inflammatory diseases. However, its clinical use is often limited by gastrointestinal side effects, vitamin B12 deficiency, and rare but serious complications such as lactic acidosis, highlighting the need for adjunctive strategies to enhance efficacy and reduce adverse effects. Curcumin, as a bioactive polyphenol, has garnered significant attention because of its extensive pharmacological activities and excellent safety profile. Curcumin modulates key intracellular signaling pathways, including nuclear factor-kappa B, mitogen-activated protein kinases, and phosphatidylinositol 3-kinase/protein kinase B, providing anti-inflammatory, antioxidant, anticancer, and metabolic regulatory effects. Nonetheless, its clinical application is constrained by poor bioavailability because of limited absorption, rapid metabolism, and systemic elimination. Recent evidence suggests that coadministration of metformin and curcumin yields synergistic therapeutic outcomes in diverse disease models. This combination improves glycemic control, mitigates oxidative stress and inflammation, and provides organ-protective effects, particularly in the liver, heart, and skin. Furthermore, it shows promise in cancer prevention and therapy, polycystic ovary syndrome management, and pain modulation, with enhanced outcomes when delivered via nanoparticle-based systems. This review aims to provide a comprehensive analysis of the combined therapeutic potential of metformin and curcumin across a spectrum of pathological conditions.
{"title":"Synergistic Therapeutic Potential of Curcumin and Metformin: a Multipathway Approach to Disease Management","authors":"Hadiseh Mohammadi , Sahar Ghoflchi , Kasim Sakran Abass , Hossein Hosseini , Amirhossein Sahebkar","doi":"10.1016/j.tjnut.2026.101362","DOIUrl":"10.1016/j.tjnut.2026.101362","url":null,"abstract":"<div><div>Metformin, a first-line pharmacologic agent for type 2 diabetes, exerts its primary antidiabetic effects by suppressing hepatic gluconeogenesis via both AMP-activated protein kinases-dependent and -independent pathways. Beyond glycemic control, metformin exhibits pleiotropic benefits, including improved insulin sensitivity, modulation of gut microbiota, and protection against various metabolic, cardiovascular, renal, neurodegenerative, and inflammatory diseases. However, its clinical use is often limited by gastrointestinal side effects, vitamin B12 deficiency, and rare but serious complications such as lactic acidosis, highlighting the need for adjunctive strategies to enhance efficacy and reduce adverse effects. Curcumin, as a bioactive polyphenol, has garnered significant attention because of its extensive pharmacological activities and excellent safety profile. Curcumin modulates key intracellular signaling pathways, including nuclear factor-kappa B, mitogen-activated protein kinases, and phosphatidylinositol 3-kinase/protein kinase B, providing anti-inflammatory, antioxidant, anticancer, and metabolic regulatory effects. Nonetheless, its clinical application is constrained by poor bioavailability because of limited absorption, rapid metabolism, and systemic elimination. Recent evidence suggests that coadministration of metformin and curcumin yields synergistic therapeutic outcomes in diverse disease models. This combination improves glycemic control, mitigates oxidative stress and inflammation, and provides organ-protective effects, particularly in the liver, heart, and skin. Furthermore, it shows promise in cancer prevention and therapy, polycystic ovary syndrome management, and pain modulation, with enhanced outcomes when delivered via nanoparticle-based systems. This review aims to provide a comprehensive analysis of the combined therapeutic potential of metformin and curcumin across a spectrum of pathological conditions.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 3","pages":"Article 101362"},"PeriodicalIF":3.8,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145989698","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}
Pub Date : 2026-01-08DOI: 10.1016/j.tjnut.2025.101350
Gabriella AM ten Have , John J Thaden, Mariëlle PKJ Engelen, Nicolaas EP Deutz
Background
Establishing the metabolic fate of nutrients from food intake is crucial for interpreting the benefits of food interventions. Using stable isotopes labeled amino acids (AA) such as L-phenylalanine (Phe) during feeding allows for the determination of first-pass splanchnic extraction (SPE) on a whole-body level (WbSPE). The relationship between this measure and the total fraction of food-derived Phe retained by the splanchnic area has not been validated.
Objective
Therefore, we compared WbSPE with the enteral-derived Phe and actual PheSPE, measured by splanchnic-trans-organ fluxes in both healthy and early sepsis recovery states.
Methods
In 25 catheterized healthy control or Pseudomonas-induced-septic pigs (±25 kg), primed-continuous intravenous infusions of L-[ring-D5]-Phe and continuous enteral infusion of an AA mixture (per kg/h: 0.031 g N, 0.78 g maltodextrin), containing L-[1-13C]-Phe, were administered for 6 h. We collected arterial, portal, and hepatic venous blood and measured plasma enrichments and tracee concentrations by liquid chromatography-mass spectrometry (LC-MS/MS). Statistical analysis was performed using GraphPad Prism. Best-fit group means from the last 3 h were compared using an unpaired t-test. The data are presented as mean [95% confidence interval].
Results
In the healthy control group, WbSPE was 38[16,61]% (P<0.0001) of the enteral-derived Phe SPE and tended to be 16[-1,34]% (P=0.0761) higher than the actual Phe tracee SPE. However, WbSPE was the same as first-pass SPE. In the septic group, WbSPE was increased 29[8,50]%, (P=0.001) whereas the actual Phe tracee SPE remained unchanged, whereas portal-drained viscera fluxes showed a diminished release of enteral-derived tracee Phe (P < 0.0001).
Conclusions
WbSPE reflects first-pass SPE rather than enteral-derived tracee SPE or the actual SPE. Our observations suggest that whole-body level calculated SPE may be challenged in estimating food-derived amino acid SPE in response to steady meal intake. During early sepsis recovery, less AA are absorbed, and this changes the dynamics between first-pass and the actual SPE.
{"title":"Altered Dynamics in Splanchnic Amino Acid Extraction During Early Sepsis Recovery in Pigs: Whole Body Compared with Interorgan Balance Assessments","authors":"Gabriella AM ten Have , John J Thaden, Mariëlle PKJ Engelen, Nicolaas EP Deutz","doi":"10.1016/j.tjnut.2025.101350","DOIUrl":"10.1016/j.tjnut.2025.101350","url":null,"abstract":"<div><h3>Background</h3><div>Establishing the metabolic fate of nutrients from food intake is crucial for interpreting the benefits of food interventions. Using stable isotopes labeled amino acids (AA) such as L-phenylalanine (Phe) during feeding allows for the determination of first-pass splanchnic extraction (SPE) on a whole-body level (WbSPE). The relationship between this measure and the total fraction of food-derived Phe retained by the splanchnic area has not been validated.</div></div><div><h3>Objective</h3><div>Therefore, we compared WbSPE with the enteral-derived Phe and actual PheSPE, measured by splanchnic-trans-organ fluxes in both healthy and early sepsis recovery states.</div></div><div><h3>Methods</h3><div>In 25 catheterized healthy control or <em>Pseudomonas</em>-induced-septic pigs (±25 kg), primed-continuous intravenous infusions of L-[ring-D<sub>5</sub>]-Phe and continuous enteral infusion of an AA mixture (per kg/h: 0.031 g N, 0.78 g maltodextrin), containing L-[1-<sup>13</sup>C]-Phe, were administered for 6 h. We collected arterial, portal, and hepatic venous blood and measured plasma enrichments and tracee concentrations by liquid chromatography-mass spectrometry (LC-MS/MS). Statistical analysis was performed using GraphPad Prism. Best-fit group means from the last 3 h were compared using an unpaired t-test. The data are presented as mean [95% confidence interval].</div></div><div><h3>Results</h3><div>In the healthy control group, WbSPE was 38[16,61]% (P<0.0001) of the enteral-derived Phe SPE and tended to be 16[-1,34]% (P=0.0761) higher than the actual Phe tracee SPE. However, WbSPE was the same as first-pass SPE. In the septic group, WbSPE was increased 29[8,50]%, (P=0.001) whereas the actual Phe tracee SPE remained unchanged, whereas portal-drained viscera fluxes showed a diminished release of enteral-derived tracee Phe (<em>P</em> < 0.0001).</div></div><div><h3>Conclusions</h3><div>WbSPE reflects first-pass SPE rather than enteral-derived tracee SPE or the actual SPE. Our observations suggest that whole-body level calculated SPE may be challenged in estimating food-derived amino acid SPE in response to steady meal intake. During early sepsis recovery, less AA are absorbed, and this changes the dynamics between first-pass and the actual SPE.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 3","pages":"Article 101350"},"PeriodicalIF":3.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948901","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}
Pub Date : 2026-01-08DOI: 10.1016/j.tjnut.2025.101346
Yannick Razafindratsima, Andry Razakandrainy, Sonia Fortin, Rindra Randremanana, Charlotte Ralison, Christèle Icard-Vernière, Nelly Fioroni, Frank T Wieringa, Claire Mouquet-Rivier
Background: Micronutrient deficiencies are a serious public health problem in early childhood in Madagascar.
Objectives: We aimed to evaluate the effects of responsive feeding (RF) and the consumption of fortified complementary foods (FCFs), either alone or combined, on hemoglobin (Hb) concentrations and micronutrient status of young children.
Methods: A 2 × 2 factorial randomized controlled intervention trial in infants (n = 706), recruited at 6-7 mo of age, was conducted. The control group received counseling on water, sanitation, and hygiene (WASH) practices, whereas the 3 intervention groups received, in addition to WASH, promotion of RF, provision of daily FCF or both (FCF + RF). Hb concentrations and micronutrient status (iron, zinc, vitamin A, and thiamine) were evaluated at baseline and at the end of the intervention after 9 mo, whereas anthropometry was assessed 3 times monthly. The impact of interventions was evaluated through generalized mixed models.
Results: Prevalence of micronutrient deficiency was high, with 85% of children affected by 1 or more deficiencies. Consumption of FCF increased concentrations of Hb (+5.43 g/L, 95% confidence interval [95% CI]: +2.52, +8.3) and retinol-binding protein (RBP: +0.09 μmol/L; 95% CI: +0.04, +0.14). Promotion of RF had only a positive effect on RBP (RBP: +0.06 μmol/L; 95% CI: +0.01, +0.11), but surprisingly, a negative impact on iron, zinc, and thiamine status was observed. There were significant interactions between RF and FCF for most indicators of micronutrient status.
Conclusions: The study confirms the potential of FCF on improving micronutrient status of young children, but surprisingly, RF tended to have a negative impact, warranting more research into appropriate RF training modules.
Registry number: The study protocol was registered under the Pan African clinical trials registry (http://www.edctp.org/pan-african-clinical-trials-registry/) under the number PACTR201906819960554.
{"title":"Effects of Consumption of Fortified Complementary Food and Promotion of Responsive Feeding on the Hemoglobin and Micronutrient Status of Young Children in a Controlled, Cluster Randomized Trial in the District of Amparafaravola in Madagascar.","authors":"Yannick Razafindratsima, Andry Razakandrainy, Sonia Fortin, Rindra Randremanana, Charlotte Ralison, Christèle Icard-Vernière, Nelly Fioroni, Frank T Wieringa, Claire Mouquet-Rivier","doi":"10.1016/j.tjnut.2025.101346","DOIUrl":"10.1016/j.tjnut.2025.101346","url":null,"abstract":"<p><strong>Background: </strong>Micronutrient deficiencies are a serious public health problem in early childhood in Madagascar.</p><p><strong>Objectives: </strong>We aimed to evaluate the effects of responsive feeding (RF) and the consumption of fortified complementary foods (FCFs), either alone or combined, on hemoglobin (Hb) concentrations and micronutrient status of young children.</p><p><strong>Methods: </strong>A 2 × 2 factorial randomized controlled intervention trial in infants (n = 706), recruited at 6-7 mo of age, was conducted. The control group received counseling on water, sanitation, and hygiene (WASH) practices, whereas the 3 intervention groups received, in addition to WASH, promotion of RF, provision of daily FCF or both (FCF + RF). Hb concentrations and micronutrient status (iron, zinc, vitamin A, and thiamine) were evaluated at baseline and at the end of the intervention after 9 mo, whereas anthropometry was assessed 3 times monthly. The impact of interventions was evaluated through generalized mixed models.</p><p><strong>Results: </strong>Prevalence of micronutrient deficiency was high, with 85% of children affected by 1 or more deficiencies. Consumption of FCF increased concentrations of Hb (+5.43 g/L, 95% confidence interval [95% CI]: +2.52, +8.3) and retinol-binding protein (RBP: +0.09 μmol/L; 95% CI: +0.04, +0.14). Promotion of RF had only a positive effect on RBP (RBP: +0.06 μmol/L; 95% CI: +0.01, +0.11), but surprisingly, a negative impact on iron, zinc, and thiamine status was observed. There were significant interactions between RF and FCF for most indicators of micronutrient status.</p><p><strong>Conclusions: </strong>The study confirms the potential of FCF on improving micronutrient status of young children, but surprisingly, RF tended to have a negative impact, warranting more research into appropriate RF training modules.</p><p><strong>Registry number: </strong>The study protocol was registered under the Pan African clinical trials registry (http://www.edctp.org/pan-african-clinical-trials-registry/) under the number PACTR201906819960554.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":"101346"},"PeriodicalIF":3.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948881","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}
Pub Date : 2026-01-08DOI: 10.1016/j.tjnut.2025.101347
Yujie Li , Weiyu Li , Jianlou Song , Qiang Jiang , Wenbin Li , Zhiqiang Wang , Xiaoli Dong , Minhao Zhang , Jianmin Yuan , Yuming Guo , Zengpeng Lv
Background
The efficacy of low-protein diets, an effective approach to the high-quality protein feed shortage, relies on precisely meeting the amino acid requirements of broilers.
Objective
This study aimed to determine the arginine requirement of WOD188 broilers fed low-protein diets and to assess the effects of arginine on growth performance, intestinal function, and nitrogen metabolism.
Methods
Experiment 1: WOD188 broilers (29-d-old, male, n = 300) were randomly assigned to a normal-protein diet or 4 low-protein diets with standardized ileal digestible arginine-to-lysine ratios (SID Arg:Lys) of 96%, 107%, 118%, and 128% (6 cages/treatment, 10 broilers/cage). After 13 d, growth performance was recorded and regarded as the primary outcome for evaluating the arginine requirement. Samples of blood, breast muscle, intestine, and chyme were collected for the analysis of serum parameters, meat quality, intestinal morphology, gene/protein expression, and intestinal microbiota. Experiment 2: A total of 90 broilers (35–37-d-old) were fed the same 5 diets and collected excreta to measure nitrogen content. Data were analyzed by one-way ANOVA and regression modeling.
Results
A dynamic requirement model for SID arginine intake (Y) was established as Y = 1.703 × BW0.70 + 0.750 × body weight gain (BWG). The optimal growth performance and peak nitrogen utilization efficiency were achieved at SID Arg:Lys 107%–115%. Low-protein diets with arginine supplementation decreased meat pH, fecal nitrogen content, serum total protein (TP) and blood urea nitrogen (BUN) concentrations (P < 0.05), while increasing intestinal villus height and NO concentrations (P < 0.05). It also upregulated intestinal CAT-2 mRNA expression, barrier-related protein (ZO-1/ Occludin) expression, and decreased interleukin 10 inflammatory factor concentrations (P < 0.05). The low-protein diet significantly reduced bacterial α-diversity (ACE and Chao1 index, P < 0.05), linear discriminant analysis (LDA) effect size analysis further identified Lactobacillus as key biomarkers LDA score > 2.0, false discovery rate (FDR)-adjusted P < 0.05).
Conclusions
This study established the dynamic arginine requirement model of WOD188 broilers fed the low-protein diet. Dietary arginine enhanced growth performance, carcass traits, and meat quality, while improving intestinal microbiota composition, barrier, and transport function, ultimately elevating nitrogen utilization efficiency.
{"title":"Arginine Requirements for WOD188 Broilers on a Low-Protein Diet: Insights from Growth Performance and Intestine Health","authors":"Yujie Li , Weiyu Li , Jianlou Song , Qiang Jiang , Wenbin Li , Zhiqiang Wang , Xiaoli Dong , Minhao Zhang , Jianmin Yuan , Yuming Guo , Zengpeng Lv","doi":"10.1016/j.tjnut.2025.101347","DOIUrl":"10.1016/j.tjnut.2025.101347","url":null,"abstract":"<div><h3>Background</h3><div>The efficacy of low-protein diets, an effective approach to the high-quality protein feed shortage, relies on precisely meeting the amino acid requirements of broilers.</div></div><div><h3>Objective</h3><div>This study aimed to determine the arginine requirement of WOD188 broilers fed low-protein diets and to assess the effects of arginine on growth performance, intestinal function, and nitrogen metabolism.</div></div><div><h3>Methods</h3><div>Experiment 1: WOD188 broilers (29-d-old, male, <em>n</em> = 300) were randomly assigned to a normal-protein diet or 4 low-protein diets with standardized ileal digestible arginine-to-lysine ratios (SID Arg:Lys) of 96%, 107%, 118%, and 128% (6 cages/treatment, 10 broilers/cage). After 13 d, growth performance was recorded and regarded as the primary outcome for evaluating the arginine requirement. Samples of blood, breast muscle, intestine, and chyme were collected for the analysis of serum parameters, meat quality, intestinal morphology, gene/protein expression, and intestinal microbiota. Experiment 2: A total of 90 broilers (35–37-d-old) were fed the same 5 diets and collected excreta to measure nitrogen content. Data were analyzed by one-way ANOVA and regression modeling.</div></div><div><h3>Results</h3><div>A dynamic requirement model for SID arginine intake (Y) was established as Y = 1.703 × BW<sup>0.70</sup> + 0.750 × body weight gain (BWG). The optimal growth performance and peak nitrogen utilization efficiency were achieved at SID Arg:Lys 107%–115%. Low-protein diets with arginine supplementation decreased meat pH, fecal nitrogen content, serum total protein (TP) and blood urea nitrogen (BUN) concentrations (<em>P</em> < 0.05), while increasing intestinal villus height and NO concentrations (<em>P</em> < 0.05). It also upregulated intestinal <em>CAT-2</em> mRNA expression, barrier-related protein (ZO-1/ Occludin) expression, and decreased interleukin 10 inflammatory factor concentrations (<em>P</em> < 0.05). The low-protein diet significantly reduced bacterial α-diversity (ACE and Chao1 index, <em>P</em> < 0.05), linear discriminant analysis (LDA) effect size analysis further identified <em>Lactobacillus</em> as key biomarkers LDA score > 2.0, false discovery rate (FDR)-adjusted <em>P</em> < 0.05).</div></div><div><h3>Conclusions</h3><div>This study established the dynamic arginine requirement model of WOD188 broilers fed the low-protein diet. Dietary arginine enhanced growth performance, carcass traits, and meat quality, while improving intestinal microbiota composition, barrier, and transport function, ultimately elevating nitrogen utilization efficiency.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 3","pages":"Article 101347"},"PeriodicalIF":3.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948932","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}
Pub Date : 2026-01-08DOI: 10.1016/j.tjnut.2025.101349
Robin P da Silva , Brandon J Eudy
Background
Dysregulated one-carbon metabolism occurs in metabolic dysfunction-associated steatotic liver disease (MASLD) and in models of liver fibrosis, but two fibrosis models display opposing methylation cycle profiles, which has been a point of confusion. Broader changes in one-carbon related metabolism and the consequent impact on transcriptional events have not been fully explored.
Objective
The objective of this study was to identify common metabolic and transcriptional profiles in methionine and choline deficient (MCD) and glycine N-methyltransferase knockout (GNMTKO) mice to help us understand molecular mechanisms that contribute to hepatic fibrosis.
Methods
Eight-wk-old male GNMTKO (C57BL6J background) and control mice were fed AIN-76 based diet (24% casein, 60% sucrose/starch, and 5% fat) for 8 wk (n = 5–6). Ten-wk-old male C57BL6J mice were fed amino acid-defined diet (based on AIN-76) with or without sufficient methionine and choline (65% sucrose/starch, 15% defined amino acid, and 10% fat) for 5 wk (n = 6). We characterized the expression of folate metabolic enzymes, measured the amino acid content in plasma and liver, performed targeted metabolomics and RNA sequencing in liver to compare metabolite and transcriptional profiles.
Results
We measured an 11-fold increase (P = 0.0067) in MTHFD1L1 and 2.8-fold (P = 0.013) MTHFS expression in liver of GNMTKO mice, matching results from our previous study in MCD mice. Liver mitochondria from GNMTKO mice had a 2-fold (P = 0.0423) higher capacity for oxidation of one-carbon units. We find common regulation of xenobiotic/metabolic sensors, growth, immune, and inflammatory pathways in our transcriptomic analysis. Statistical analysis was performed using an unpaired Student’s t-test with Welch’s correction, and RNA sequencing data were analyzed using the method of Benjamini-Hochberg.
Conclusions
We identify a common dysregulation in folate metabolism in two widely used rodent models of liver fibrosis and highlight the consequent metabolic disturbances. Analysis of hepatic transcriptional profiles of MCD and GNMTKO mice reveals novel association of the transcriptional regulators STAT5b, AhR, and ARNT with liver fibrosis.
{"title":"The Hepatic Transcriptomes of Two Mouse Models of Liver Fibrosis Reveal Shared Molecular Patterns Associated with a Common Dysregulation of Folate Metabolism","authors":"Robin P da Silva , Brandon J Eudy","doi":"10.1016/j.tjnut.2025.101349","DOIUrl":"10.1016/j.tjnut.2025.101349","url":null,"abstract":"<div><h3>Background</h3><div>Dysregulated one-carbon metabolism occurs in metabolic dysfunction-associated steatotic liver disease (MASLD) and in models of liver fibrosis, but two fibrosis models display opposing methylation cycle profiles, which has been a point of confusion. Broader changes in one-carbon related metabolism and the consequent impact on transcriptional events have not been fully explored.</div></div><div><h3>Objective</h3><div>The objective of this study was to identify common metabolic and transcriptional profiles in methionine and choline deficient (MCD) and glycine N-methyltransferase knockout (GNMTKO) mice to help us understand molecular mechanisms that contribute to hepatic fibrosis.</div></div><div><h3>Methods</h3><div>Eight-wk-old male GNMTKO (C57BL6J background) and control mice were fed AIN-76 based diet (24% casein, 60% sucrose/starch, and 5% fat) for 8 wk (<em>n</em> = 5–6). Ten-wk-old male C57BL6J mice were fed amino acid-defined diet (based on AIN-76) with or without sufficient methionine and choline (65% sucrose/starch, 15% defined amino acid, and 10% fat) for 5 wk (<em>n</em> = 6). We characterized the expression of folate metabolic enzymes, measured the amino acid content in plasma and liver, performed targeted metabolomics and RNA sequencing in liver to compare metabolite and transcriptional profiles.</div></div><div><h3>Results</h3><div>We measured an 11-fold increase (<em>P</em> = 0.0067) in MTHFD1L1 and 2.8-fold (<em>P</em> = 0.013) MTHFS expression in liver of GNMTKO mice, matching results from our previous study in MCD mice. Liver mitochondria from GNMTKO mice had a 2-fold (<em>P</em> = 0.0423) higher capacity for oxidation of one-carbon units. We find common regulation of xenobiotic/metabolic sensors, growth, immune, and inflammatory pathways in our transcriptomic analysis. Statistical analysis was performed using an unpaired Student’s t-test with Welch’s correction, and RNA sequencing data were analyzed using the method of Benjamini-Hochberg.</div></div><div><h3>Conclusions</h3><div>We identify a common dysregulation in folate metabolism in two widely used rodent models of liver fibrosis and highlight the consequent metabolic disturbances. Analysis of hepatic transcriptional profiles of MCD and GNMTKO mice reveals novel association of the transcriptional regulators STAT5b, AhR, and ARNT with liver fibrosis.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 3","pages":"Article 101349"},"PeriodicalIF":3.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948958","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}
Pub Date : 2026-01-08DOI: 10.1016/j.tjnut.2025.101348
Courtney M Holdaway , Amy Vo , Kelly-Ann Leonard , Randal Nelson , Aducio Thiesen , Yi Fan , Camila S Marcolla , Robin D Clugston , Benjamin P Willing , Rene L Jacobs
Background
Ethanolamine (Etn), a precursor of phosphatidylethanolamine (PE), may alter hepatic lipid homeostasis and gut health; its dietary effects remain undefined.
Objective
The objective of this study was to determine the effects of dietary Etn on lipid and glucose metabolism and liver/gut health in high-fat diet (HFD)–fed mice, complemented by in vitro hepatocyte assays.
Methods
Ten-wk-old C57BL/6 mice (20 male, 18 female) were fed ad libitum HFD (45% energy from fat) with [Ethanolamine supplementation (ES-group)] or without (CON-group) Etn (8 g/kg diet) for 10 wk. Outcomes included body/liver weight, glucose tolerance test (GTT) results, plasma phosphatidylcholine (PC)/cholesteryl ester (CE)/triacylglycerol (TG) concentrations, hepatic TG/PC/PE concentrations, hepatic endoplasmic reticulum (ER)-stress, and inflammation markers, jejunal morphology/barrier/inflammation genes, and fecal microbiota (α/β diversity). HuH7 cells received 20 μM or 5 mM Etn to assess TG/PC/PE synthesis. Statistics: repeated-measures analysis of variance (ANOVA) (GTT), t-test or Wilcoxon (other endpoints), permutational multivariate analysis of variance (PERMANOVA) (β diversity); α=0.05.
Results
ES increased hepatic TG in females by 230% compared with CON (P = 0.001), and trended higher in males (P = 0.054); hepatic PC and PE masses were unchanged. In ES males, GTT area under the curve decreased by 22.6% (P = 0.037), and plasma PC, CE, and TG were reduced by: PC −16.6%, CE −24.5%, TG −25.9%, respectively (all P < 0.05). ES males showed higher hepatic Tnf and Cd68 and increased C/EBP homologous protein (CHOP) (all P < 0.05). In vitro, Etn did not alter hepatocellular TG, PC, or PE synthesis (all P > 0.05). Female ES mice exhibited altered fecal β-diversity (PERMANOVA P = 0.006) with early jejunal inflammatory signals (Tnf ↑; P = 0.055).
Conclusions
Dietary Etn modifies hepatic lipid storage and gut microbiota in a sex-dependent manner and improves glucose tolerance in males, whereas in vitro data indicate no direct effect on hepatocyte lipid synthesis.
{"title":"Dietary Ethanolamine Increases Hepatic Lipid Accumulation in Mice Fed a High-Fat Diet","authors":"Courtney M Holdaway , Amy Vo , Kelly-Ann Leonard , Randal Nelson , Aducio Thiesen , Yi Fan , Camila S Marcolla , Robin D Clugston , Benjamin P Willing , Rene L Jacobs","doi":"10.1016/j.tjnut.2025.101348","DOIUrl":"10.1016/j.tjnut.2025.101348","url":null,"abstract":"<div><h3>Background</h3><div>Ethanolamine (Etn), a precursor of phosphatidylethanolamine (PE), may alter hepatic lipid homeostasis and gut health; its dietary effects remain undefined.</div></div><div><h3>Objective</h3><div>The objective of this study was to determine the effects of dietary Etn on lipid and glucose metabolism and liver/gut health in high-fat diet (HFD)–fed mice, complemented by in vitro hepatocyte assays.</div></div><div><h3>Methods</h3><div>Ten-wk-old C57BL/6 mice (20 male, 18 female) were fed ad libitum HFD (45% energy from fat) with [Ethanolamine supplementation (ES-group)] or without (CON-group) Etn (8 g/kg diet) for 10 wk. Outcomes included body/liver weight, glucose tolerance test (GTT) results, plasma phosphatidylcholine (PC)/cholesteryl ester (CE)/triacylglycerol (TG) concentrations, hepatic TG/PC/PE concentrations, hepatic endoplasmic reticulum (ER)-stress, and inflammation markers, jejunal morphology/barrier/inflammation genes, and fecal microbiota (α/β diversity). HuH7 cells received 20 μM or 5 mM Etn to assess TG/PC/PE synthesis. Statistics: repeated-measures analysis of variance (ANOVA) (GTT), t-test or Wilcoxon (other endpoints), permutational multivariate analysis of variance (PERMANOVA) (β diversity); α=0.05.</div></div><div><h3>Results</h3><div>ES increased hepatic TG in females by 230% compared with CON (<em>P</em> = 0.001), and trended higher in males (<em>P</em> = 0.054); hepatic PC and PE masses were unchanged. In ES males, GTT area under the curve decreased by 22.6% (<em>P</em> = 0.037), and plasma PC, CE, and TG were reduced by: PC −16.6%, CE −24.5%, TG −25.9%, respectively (all <em>P</em> < 0.05). ES males showed higher hepatic <em>Tnf</em> and <em>Cd68</em> and increased C/EBP homologous protein (CHOP) (all <em>P</em> < 0.05). In vitro, Etn did not alter hepatocellular TG, PC, or PE synthesis (all <em>P</em> > 0.05). Female ES mice exhibited altered fecal β-diversity (PERMANOVA <em>P</em> = 0.006) with early jejunal inflammatory signals (<em>Tnf</em> ↑; <em>P</em> = 0.055).</div></div><div><h3>Conclusions</h3><div>Dietary Etn modifies hepatic lipid storage and gut microbiota in a sex-dependent manner and improves glucose tolerance in males, whereas in vitro data indicate no direct effect on hepatocyte lipid synthesis<strong>.</strong></div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 3","pages":"Article 101348"},"PeriodicalIF":3.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948938","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}
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