Journal of Nutritional Biochemistry最新文献

{"title":"Early postnatal overnutrition as a contributor to metabolic dysregulation: insights into hepatic epigenetic mechanisms.","authors":"Wen Zheng, Nan Zhou, Jiasi Kuang, Susu Du, Dandan Zhu, Ru Ling, Chunyang Zhang, YueShu Wang, Wei Zhou, Xiaonan Li","doi":"10.1016/j.jnutbio.2025.110022","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110022","url":null,"abstract":"<p><strong>Objective: </strong>This study evaluated the effects of postnatal overnutrition during lactation on hepatic DNA methylation patterns and their relationship with hepatic metabolic disorders.</p><p><strong>Methods: </strong>At postnatal day 3, male rats were randomly divided into normal litters (NL, 10 pups per litter) or small litters (SL, 3 pups per litter). Weight and insulin resistance were assessed at week 3 and week 13. Whole-genome bisulfite sequencing was used to detect alterations in hepatic DNA methylation levels, and enrichment analysis for differentially methylated genes (DMGs) was conducted. The methyl donor for DNA methylation, hepatic S-adenosylmethionine (SAMe) and serum methionine (Met) content were assessed by ELISA. The mRNA and protein expression levels of methionine adenosyltransferase I, alpha (Mat1a), a gene associated with SAMe synthesis, were examined.</p><p><strong>Results: </strong>Rats that had postnatal overnutrition induced by small-litter rearing exhibited significant weight gain, insulin resistance and increased hepatic lipid deposition alongside reduced hepatic glycogen content. At week 3, the overall DNA methylation levels of the liver were notably reduced in the SL rats, with the differentially methylated regions (DMRs) primarily located in the genomic and intergenic regions. The DMGs were significantly enriched in the phosphatidylinositol (PI) and insulin resistance (IR) pathway. As the DNA methylation level decreased, the serum Met levels increased abnormally, while the hepatic SAMe content, glutathione (GSH) and Mat1a gene expression decreased significantly.</p><p><strong>Conclusion: </strong>Postnatal overnutrition leads to an aberrant hepatic DNA methylation pattern, which could contribute to persistent obesity and metabolic liver disorders by potentially regulating genes in the PI and IR pathways.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110022"},"PeriodicalIF":4.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144618557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enriched environment exposure restores behavioral alterations and transcriptional dysregulation of hippocampal steroidogenic enzymes in a small litter model.","authors":"Maria Florencia Rossetti, Rocío Schumacher, Guillermina Canesini, Pamela Fernández, Luisa Gaydou, Cora Stoker, Jorge Guillermo Ramos","doi":"10.1016/j.jnutbio.2025.110024","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110024","url":null,"abstract":"<p><p>We previously reported that rats raised in small litters (SL) exhibited increased anxiety-like behavior and poor performance in the episodic-like memory (ELM) test compared to normal litters (NL). Additionally, mRNA expression of aromatase was increased, and 5α-reductase 1 was reduced in the dentate girus (DG) of SL compared to NL rats. In this work, the objective was to analyze whether environmental enrichment (EE) can reverse or attenuate the behavioral and molecular effects observed in SL animals. Thus, male rats were raised in small litters (4 pups/mother; SL), where pups consumed larger amounts of milk and gained more body weight compared to rats raised in normal litters (10 pups/mother; NL). On postnatal day (PND) 21, male rats were housed under standard conditions (SE, 4 rats/cage) or EE (8 rats/cage). For EE, cages were equipped with objects and tunnels that were changed daily. At PND75, the animals underwent locomotion activity, ELM and elevated plus maze (EPM) tests. At PND90, the animals were euthanized, and their brains were microdissected. DG, CA1, and CA3 regions were isolated for mRNA quantification and methylation studies. We found that EE attenuates anxiety-like behavior and rescues spatial memory deficits in SL animals. Furthermore, EE prevented the increase in aromatase and decline in 5α-reductase 1, expression associated with SL. Some of these changes were correlated with alterations in methylation patterns of the promoter regions of these genes. These findings demonstrate that environmental interventions can mitigate the long-term effects observed in the SL model and restore brain and behavioral functions.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110024"},"PeriodicalIF":4.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Saponin on Testes Oxidative Stress, Apoptosis, and Steroid Hormone Synthesis Pathway in Bile Duct Ligation Model of Obstructive Cholestasis in male Wistar rats.","authors":"Helia Mavaddat, Mahsa Ale-Ebrahim, Diba Sabouni Aghdam","doi":"10.1016/j.jnutbio.2025.110020","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110020","url":null,"abstract":"<p><strong>Background: </strong>Cholestasis occurs when bile flow is disrupted and toxic bile acids accumulate in the liver. This leads to systemic oxidative stress that may affect other organs including the testes. Cholestasis can cause testicular dysfunction. Saponins have antioxidant capacity and can elevate testosterone levels.</p><p><strong>Purpose: </strong>In this study, a bile duct ligation (BDL) model of cholestasis has been used to assess the effects of cholestasis on antioxidant activity, apoptosis, steroid hormone synthesis pathway, and histopathological changes in testes and then evaluate the capability of saponin in attenuation of the injuries.</p><p><strong>Study design: </strong>We performed an in vivo study and experimental groups were as follows: control (healthy rats+0.5 ml distilled water); sham (laparotomy without BDL); saponin control (200 or 400 mg/kg); BDL; and saponin treatment (BDL rats+200 or 400 mg/kg saponin).</p><p><strong>Methods: </strong>Catalase (CAT) and superoxide dismutase (SOD) activity was evaluated by enzyme-linked immunosorbent assay (ELISA) and protein expression was assessed by Western blotting. Hematoxylin & Eosin staining was done for histopathological analysis.</p><p><strong>Results: </strong>The results indicated that BDL reduced CAT and SOD activity and stimulated apoptosis. Moreover, protein expression of Steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), and 17β-hydroxysteroid dehydrogenase (17β-HSD) was down-regulated and histopathological changes occurred. Saponin could increase SOD and CAT activity and decrease apoptosis. Also, StAR, 17β-HSD, and 3β-HSD expression were increased by saponin. In addition, histological changes were ameliorated by saponin treatment.</p><p><strong>Conclusion: </strong>all these data indicate that saponin may effectively reverse the modifications caused by cholestasis in the testes.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110020"},"PeriodicalIF":4.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline 25-Hydroxyvitamin D as a Stronger Protector Against Type 2 Diabetes in the Context of Hyperuricemia and Gout: A Cohort Study Based on the UK Biobank.","authors":"Yingdong Han, Juan Wu, Menghui Yao, Tiange Xie, Zhikai Li, He Zhao, Yun Zhang, Xuejun Zeng","doi":"10.1016/j.jnutbio.2025.110021","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110021","url":null,"abstract":"<p><strong>Background: </strong>To elucidate the association between Vitamin D and the risk of Type 2 diabetes (T2D) in individuals with hyperuricemia or gout.</p><p><strong>Methods: </strong>A total of 43731 patients with hyperuricemia and 9695 with gout were included to assess the association between Vitamin D levels and T2D risk. Serum 25(OH)D (nmol/L) concentrations were measured. Multivariable logistic regression, cumulative incidence curves, Cox proportional-hazards models, and restricted cubic spline analysis were used to evaluate the relationship between 25(OH)D and T2D risk. Sensitivity and stratified analyses were performed to ensure the robustness of the findings.</p><p><strong>Results: </strong>Higher serum 25(OH)D concentration was associated with lower risk of baseline T2D. During a median follow-up of 14.27 years for hyperuricemia patients and 14.09 years for gout patients, 4617 and 1072 new-onset T2D cases were documented, respectively. An inverse, nonlinear dose-response relationship was found between 25(OH)D and incident T2D in hyperuricemia patients. Compared to participants with 25(OH)D < 25 nmol/L, the adjusted HR for those with 25(OH)D > 75 nmol/L was 0.62 (0.54, 0.72). In gout patients, the protective effect of 25(OH)D was even more pronounced [HR: 0.45(0.32, 0.62)]. Sensitivity analyses confirmed the robustness of our findings. Significant interactions were observed with age, smoking, and cardiovascular disease, while genetic susceptibility showed no interaction. The protective effect of 25(OH)D (per 10 nmol/L increase) was stronger in hyperuricemia patients aged <65 years [<65 years: 0.91 (0.89, 0.93), ≥65 years 0.96 (0.93, 0.99)] and in never smokers [Never: 0.92 (0.89, 0.95), Current: 1.00 (0.95, 1.06)]. Among gout patients, the effect was more evident in those without cardiovascular disease [No: 0.86 (0.82, 0.90), Yes: 0.92 (0.84, 1.00)].</p><p><strong>Conclusions: </strong>Higher serum 25(OH)D concentration is significantly associated with a lower risk of incident T2D in patients with hyperuricemia or gout, and this association is especially pronounced among younger individuals, non-smokers and those without cardiovascular disease.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110021"},"PeriodicalIF":4.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated multi-omics analysis reveals the effect of glucose selenol improves rat immunity.","authors":"Xinyi Yang, Jinzhou Huang, Zhi Zeng, Si Sun, Juan Wang, Zhi Wang","doi":"10.1016/j.jnutbio.2025.110023","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110023","url":null,"abstract":"<p><p>This study aimed to investigate the effects of glucose selenol (SeGlu) on the immune function of rats, with a particular focus on the spleen. Rats were randomly divided into CK (deionized water, oral), Se0.15 group (0.15 mg/L SeGlu, oral), and Se0.4 group (0.4 mg/L SeGlu, oral) for 30 days continuously. 0.15 mg/L SeGlu significantly increased the serum antioxidant levels and the levels of IgM and IgG. The Se0.4 group upregulated the inflammatory factor levels of IL-2 and IL-6, and both concentrations significantly reduced the serum TNF-α level. Transcriptome analysis indicated that the supplementation of SeGlu could affect three types of proteins: peptidases, tumor necrosis factor receptors, and transmembrane transport proteins. KEGG enrichment discovered pathway annotations directly or indirectly related to the immune process, especially phagosomes, natural killer cell-mediated cytotoxicity, and nod-like receptor signaling pathways. We identified 59 SeGlu target differentially expressed genes and 8 (NEG) and 20 (POS) co-expressed differentially expressed metabolites. Immunoglobulin-related DEGs were concentrated in the transcription factor family V-set, and were identified on chromosome 6. In addition, metagenome sequencing showed that SeGlu treatment increased abundance of Roseburia, Ruminococcus, Eubacterium, Coprobacillus, and Intestinimonas at the genus level. Spearman correlation analysis results showed that the modulatory effects of SeGlu on D-proline were related to the regulation of Roseburia, Clostridium, Eubacterium Coprobacillus, Butyricimonas, and Muribaculum. Overall, the analyses of rat physiology, transcriptome, metabolome, and metagenome offer new insights into Se on rat immunity. SeGlu provides beneficial immune protection and is a promising organic selenium enrichment additive.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110023"},"PeriodicalIF":4.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calycosin-7-O-β-D-glucoside alleviates non-alcoholic fatty liver disease by regulating short-chain fatty acids metabolism and metabolic regulators.","authors":"Yanping Zeng, Xinrun Huang, Yuci Ma, Xiaodie Di, Zhao Li, Hebin Wang, Xiaodong Wei","doi":"10.1016/j.jnutbio.2025.110018","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110018","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is a metabolic stress liver injury disease caused by excessive fat deposition in hepatocytes. Astragalus memeranaceus Fisch., mainly consists of flavonoids, is considered to have good liver protection effects. This study aimed to explore the active ingredients and possible mechanisms of Astragalus flavone in the treatment of NAFLD. Network pharmacology and molecular docking were used to screen the active ingredients and targets of Astragalus flavone in the treatment of NAFLD, and were verified in vivo high-fat diet-induced mouse models. There were 89 predicted targets of 10 main compounds of Astragalus flavone in treating NAFLD, and the core genes involved PPAR-γ. Molecular docking results showed that all the 10 main components of Astragalus flavone had a strong binding activity with PPAR-γ, among which CG had the strongest binding ability. In vivo results showed that CG inhibited obesity, reduced the disorder of glucose and lipid metabolism, alleviated liver function injury and lipid accumulation, and improved the oxidative stress and inflammatory response of NAFLD mice, playing a positive role in the treatment of NAFLD. In addition, CG promoted the expression of AMPK, PPAR-γ, and Nrf2, inhibited the expressions of NF-кB, and regulated the metabolism of short-chain fatty acids (SCFAs) in NAFLD. In conclusion, CG, the main active component of Astragalus flavone, exerts a positive therapeutic effect on NAFLD, which is related to CG altering various energy sensors and metabolic regulators (PPAR-γ, AMPK, NF-кB, and Nrf2) that contribute to changes in intestinal SCFAs.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110018"},"PeriodicalIF":4.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naringin attenuates myocardial ischemia-reperfusion injury by promoting mitochondrial translocation of NDUFS1 and suppressing cardiac microvascular endothelial cell ferroptosis.","authors":"Xue Guan, Zhenyu Yang, Jinming Wang, Wei Lu, Shilin Wang, Mi Yang, Pengbo Sun, Wenfu Hu, Liming Yang, Hong Li","doi":"10.1016/j.jnutbio.2025.110019","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110019","url":null,"abstract":"<p><strong>Purpose: </strong>Cardiac microvascular injury plays a pivotal role in the progression of myocardial ischemia-reperfusion injury (MI/RI). Previous studies have demonstrated the cardioprotective effects of naringin (Nar) in cardiovascular diseases. However, the involvement of cardiac microvessels in Nar-mediated protection against MI/RI remains unexplored. This study aimed to investigate the impact of Nar on the function of cardiac microvascular endothelial cells (CMECs) in MI/RI rat.</p><p><strong>Methods: </strong>An MI/RI model was established in rats through ligation of the left anterior descending artery for 45 min followed by 6 h of reperfusion. In vitro, a hypoxia-reoxygenation (H/R) model was established in CMECs by subjecting them to 12 h of hypoxia and 24 h of reoxygenation. A comprehensive set of experimental techniques was employed, including qRT-PCR, western blotting, transmission electron microscopy (TEM), proteomic analysis, ELISA, TTC staining, immunohistochemistry, immunofluorescence, molecular docking, and molecular dynamics simulations.</p><p><strong>Results: </strong>Our results revealed that Nar significantly enhances cardiac microvascular function by suppressing ferroptosis in CMECs during MI/RI. Mechanistically, phosphorylation of interferon regulatory factor 3 (IRF3) was downregulated in both the hearts of MI/RI rats and CMECs exposed to H/R. Nar effectively upregulated IRF3 phosphorylation, thereby activating the SLC7A11/Gpx4 signaling pathway. Furthermore, Nar facilitated the translocation of NADH ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) from the cytosol to the mitochondria, enhancing mitochondrial function and mitigating ferroptosis in H/R-treated CMECs.</p><p><strong>Conclusion: </strong>Nar promoted mitochondrial translocation of NDUFS1, thereby restoring mitochondrial function and inhibited CMECs ferroptosis via activation of the IRF3/SLC7A11/Gpx4 axis.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110019"},"PeriodicalIF":4.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Astragalus Polysaccharide Alleviated Experimental Colitis Involved mTreg cells and the mTOR/HIF-1α Pathway.","authors":"Miaohua Liu, Jiaojiao Luo, Jiaqi Huang, Xiyan Zhu, Duanyong Liu, Jian Long, Bailin Deng, Bugao Zhou, Haimei Zhao","doi":"10.1016/j.jnutbio.2025.110010","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110010","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the effect of astragalus polysaccharide (APS) in the treatment of ulcerative colitis (UC) and its molecular mechanisms, particularly through the ability to regulate Treg cell-glycolytic interactions.</p><p><strong>Materials and methods: </strong>BALB/c mice were used to establish DSS-induced UC model, and administered with APS (200 mg/kg) as a therapeutic intervention. During the study, flow cytometry was employed to analyze the changes in the proportions of Treg cells and their related subpopulations in the spleens of mice. Additionallyand the expression levels of various cytokines in the colon tissues were detectedsimultaneously. To further investigate the mechanism of action of APS, RNA sequencing was also performed on the colon tissues, and the regulatory effects of APS on glycolysis and mTOR/HIF-1α signaling pathway were revealed by KEGG pathway analysis, western blot, RT-qPCR and other techniques.</p><p><strong>Key findings: </strong>In this study, we found that APS not only substantially ameliorated the adverse symptoms in UC mice, but also promoted the expression of anti-inflammatory cytokines and suppressed the levels of pro-inflammatory cytokines by regulating the distribution of Treg cells and their subpopulations. Furthmore, the molecular mechanism by which APS exerts its protective effects by inhibiting glycolysis and mTOR/HIF-1α signaling pathway was revealed through RNA sequencing, KEGG pathway analysis, and other techniques.</p><p><strong>Significance: </strong>The study revealed that APS effectively ameliorated the symptoms of UC in mice by regulating Treg cells, inhibiting glycolysis and mTOR/HIF-1α signaling pathway, providing a scientific basis and potential therapeutic target for the application of APS in UC treatment.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110010"},"PeriodicalIF":4.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcitriol/Vitamin D Receptor Ameliorates Fructose-Induced Enteritis-Hepatitis Axis Dysregulation in Mice.","authors":"Jiayu Yu, Hongwei Zhu, Xin Yu, Yang Liu, Jianlong Zhang, Linlin Jiang, Xingxiao Zhang","doi":"10.1016/j.jnutbio.2025.110017","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110017","url":null,"abstract":"<p><p>Emerging evidence associates excessive fructose consumption with intestinal inflammation and metabolic dysfunction-associated steatotic liver disease (MASLD), though the underlying mechanisms remain elusive. This preclinical study systematically investigated the therapeutic potential of calcitriol/vitamin D receptor (VDR) signaling in counteracting fructose-induced gut-liver axis dysregulation using female C57BL/6J mice. Experimental groups included: (1) Control (C), (2) Fructose (F; 20% w/v fructose water for 8 weeks), (3) Fructose+Calcitriol (F+V; 300 ng/kg calcitriol gavage during weeks 4-8), and (4) Calcitriol alone (V). Key findings revealed that chronic fructose exposure induced gut microbiota dysbiosis (characterized by decreased Firmicutes/Bacteroidetes ratio), compromised intestinal barrier integrity through downregulation of tight junction proteins, depleted secretory cells (Goblet/Paneth cells), and triggered apoptosis with concomitant elevation of pro-inflammatory cytokines (TNF-α, IL-6). These intestinal alterations culminated in endotoxemia-mediated hepatic inflammation and fibrogenesis, accompanied by persistent NF-κB pathway activation. Notably, calcitriol intervention significantly restored VDR expression, enhanced autophagic flux, stimulated mucin/antimicrobial peptide production, and suppressed NF-κB-mediated inflammatory responses. In vitro validation using Caco2 and RAW264.7 cells demonstrated that VDR activation effectively reversed fructose-impaired autophagy and NF-κB hyperactivation. Microbiome analysis further indicated calcitriol's partial normalization of fructose-induced microbial shifts, suggesting microbiota-mediated mechanisms. Collectively, these findings establish that calcitriol/VDR signaling mitigates fructose-driven gut-liver axis dysfunction through coordinated regulation of autophagy, mucosal defense systems, and inflammatory pathways. This mechanistic framework positions the VDR pathway as a promising therapeutic target for enteritis-hepatitis axis disorders, warranting further clinical investigation.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110017"},"PeriodicalIF":4.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leucine and glutamic acid attenuate the dextran sulfate sodium-induced colitis in mice by modulating the inflammatory response and energy metabolism processes.","authors":"Jianhui Feng, Wenhao Cao, Zhenhua Wang, Bo Xu, Gang Li, Mei Li","doi":"10.1016/j.jnutbio.2025.110016","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110016","url":null,"abstract":"<p><p>Ulcerative colitis, a multifactorial chronic condition of the gastrointestinal tract, has seen increasing interest in dietary intervention as part of its treatment strategy. In this study, we utilized a Dextran Sodium Sulfate (DSS)-induced acute colitis mouse model to assess the impact of leucine and glutamic acid on mucosal ulceration, inflammatory cell infiltration, and proteomic alterations in colon tissue. The results indicated that both glutamic acid and leucine alleviate the symptoms of colitis by reducing the histological scores of mice colon, promoting the expression of anti-inflammatory cytokines (IL-4 and IL-10) and suppressing the expression of pro-inflammatory cytokines (TGF-β and TNF-α). A total of 8576 proteins were detected, with 315 proteins showing significant differences between glutamic acid and model, and with371 proteins showing significant differences between leucine and the model. These common significantly different proteins were mainly enriched with oxidative phosphorylation pathway as well as immunity.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110016"},"PeriodicalIF":4.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}