Pub Date : 2025-12-13DOI: 10.1016/j.jnutbio.2025.110231
Ying Liu , Dandan Pan , Pinyan Zhang , Yuting Shao , Yinhua Kong , Zhenzhou Jiang , Wenjing Zhu , Houwen Wang , Xinghan Liu , Sitong Qian , Tao Wang , Xia Zhu , Tingting Yang , Qian Lu
Glomerular podocytes injury represents a critical pathological hallmark of diabetic kidney disease (DKD), in which lipotoxicity plays a central pathogenic role. Our previous investigations in type 2 diabetes mellitus (T2DM) have demonstrated that Jujuboside A (Ju A), a triterpene saponin isolated from Semen Ziziphi Spinosae (SZS), exerted dual therapeutic effects in T2DM by ameliorating hepatic steatosis and renal dysfunction. However, the role of podocytes lipid metabolism in Ju A-mediated protection against DKD remain undefined prior to the present study. In this work, we reported that Ju A significantly attenuated glomerular podocytes injury and lipotoxicity in DKD, while concurrently improving renal function and preserving glomerular morphology. Mechanistically, Yin Yang 1 (YY1)-mediated alleviation of lipotoxicity contributed to the protective effect of Ju A against glomerular podocytes injury, primarily by promoting intracellular cholesterol transport and efflux. In conclusion, our findings demonstrated that Ju A mitigated lipid overload in glomerular podocytes by modulating cholesterol homeostasis via YY1, which not only intercepted the pathological progression of DKD but also provided a potential therapeutic target (YY1) and candidate agent (Ju A) for DKD intervention.
{"title":"Jujuboside A ameliorates glomerular podocytes lipotoxicity in diabetic mice by YY1-mediated promotion of intracellular cholesterol transport and efflux","authors":"Ying Liu , Dandan Pan , Pinyan Zhang , Yuting Shao , Yinhua Kong , Zhenzhou Jiang , Wenjing Zhu , Houwen Wang , Xinghan Liu , Sitong Qian , Tao Wang , Xia Zhu , Tingting Yang , Qian Lu","doi":"10.1016/j.jnutbio.2025.110231","DOIUrl":"10.1016/j.jnutbio.2025.110231","url":null,"abstract":"<div><div>Glomerular podocytes injury represents a critical pathological hallmark of diabetic kidney disease (DKD), in which lipotoxicity plays a central pathogenic role. Our previous investigations in type 2 diabetes mellitus (T2DM) have demonstrated that Jujuboside A (Ju A), a triterpene saponin isolated from Semen <em>Ziziphi Spinosae</em> (SZS), exerted dual therapeutic effects in T2DM by ameliorating hepatic steatosis and renal dysfunction. However, the role of podocytes lipid metabolism in Ju A-mediated protection against DKD remain undefined prior to the present study. In this work, we reported that Ju A significantly attenuated glomerular podocytes injury and lipotoxicity in DKD, while concurrently improving renal function and preserving glomerular morphology. Mechanistically, Yin Yang 1 (YY1)-mediated alleviation of lipotoxicity contributed to the protective effect of Ju A against glomerular podocytes injury, primarily by promoting intracellular cholesterol transport and efflux. In conclusion, our findings demonstrated that Ju A mitigated lipid overload in glomerular podocytes by modulating cholesterol homeostasis via YY1, which not only intercepted the pathological progression of DKD but also provided a potential therapeutic target (YY1) and candidate agent (Ju A) for DKD intervention.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110231"},"PeriodicalIF":4.9,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763162","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}
Pub Date : 2025-12-12DOI: 10.1016/j.jnutbio.2025.110235
Qing Jiang
The gut microbiota plays an important role in host health and dysbiosis contributes to disease development. Natural forms of vitamin E consist of eight lipophilic antioxidants, i.e., alpha-, beta-. gamma- and delta-tocopherol (αT, βT, γT and δT) and alpha-, beta-. gamma- and delta-tocotrienol (αTE, βTE, γTE and δTE). Vitamin E forms and their metabolites including 13′-carboxychromanols (13′-COOHs) have been shown to possess anti-inflammatory activities. Interestingly, recent human and animal studies reveal that vitamin E forms and δTE-13′-COOH (metabolite of δTE) can modulate gut microbiota. Specifically, supplementation of αT, γT, tocotrienols or δTE-13′-COOH elevated some beneficial bacteria or attenuated disease-associated decrease of probiotics including butyrate producers. This review focuses on the current knowledge of the effects of different forms of vitamin E and δTE-13′-COOH on gut microbiome. Although the mechanisms underlying modulation of gut microbiota remain to be determined, this author proposes that promotion of beneficial gut microbes by vitamin E forms may in part be rooted in their antioxidant and anti-inflammatory activities as well as protection of intestinal barrier integrity, and that the modulatory effects on gut microbes likely contributes to vitamin E-facilitated disease prevention. Finally, this review discusses knowledge gaps and future research efforts needed to uncover how vitamin E forms interact with gut microbiota and utilize such knowledge for improving human health.
{"title":"The effects of different forms of vitamin E on gut microbiota, mechanisms, and implications in disease prevention","authors":"Qing Jiang","doi":"10.1016/j.jnutbio.2025.110235","DOIUrl":"10.1016/j.jnutbio.2025.110235","url":null,"abstract":"<div><div>The gut microbiota plays an important role in host health and dysbiosis contributes to disease development. Natural forms of vitamin E consist of eight lipophilic antioxidants, <em>i.e.</em>, alpha-, beta-. gamma- and delta-tocopherol (αT, βT, γT and δT) and alpha-, beta-. gamma- and delta-tocotrienol (αTE, βTE, γTE and δTE). Vitamin E forms and their metabolites including 13′-carboxychromanols (13′-COOHs) have been shown to possess anti-inflammatory activities. Interestingly, recent human and animal studies reveal that vitamin E forms and δTE-13′-COOH (metabolite of δTE) can modulate gut microbiota. Specifically, supplementation of αT, γT, tocotrienols or δTE-13′-COOH elevated some beneficial bacteria or attenuated disease-associated decrease of probiotics including butyrate producers. This review focuses on the current knowledge of the effects of different forms of vitamin E and δTE-13′-COOH on gut microbiome. Although the mechanisms underlying modulation of gut microbiota remain to be determined, this author proposes that promotion of beneficial gut microbes by vitamin E forms may in part be rooted in their antioxidant and anti-inflammatory activities as well as protection of intestinal barrier integrity, and that the modulatory effects on gut microbes likely contributes to vitamin E-facilitated disease prevention. Finally, this review discusses knowledge gaps and future research efforts needed to uncover how vitamin E forms interact with gut microbiota and utilize such knowledge for improving human health.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110235"},"PeriodicalIF":4.9,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145756935","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}
Pub Date : 2025-12-11DOI: 10.1016/j.jnutbio.2025.110233
Laura Elaine Strittmatter , Alban Piotrowsky , Luigi Marongiu , Sascha Venturelli , Christian Leischner
Among the many macro- and micronutrients contained in cow's milk, one of the most important is the lipid fraction. While the nutritional and physiological benefits of milk consumption after the first years of life are the subject of some debate, there also appear to be conflicting views on the health aspects of the milk lipids, including their involvement in cancer.
Positive in vitro and/or in vivo data on growth-inhibiting or cytotoxic effects are available for lipid components of milk such as sphingomyelins and their degradation products or various hydroxy fatty acids. Isomers of linoleic acid and branched-chain fatty acids have also been shown to have anticarcinogenic potential in animal models by inducing apoptosis.
On the other hand, there is evidence of an association between increased cancer mortality and the consumption of high-fat milk, which contradicts the tumor-protecting effects observed in vitro and in vivo. Consumption of high-fat dairy products appears to be associated with an increased risk of developing types of cancer compared to low-fat dairy or other topical soy-based alternatives.
There are ambiguous results for an anticarcinogenic effect of various lipid constituents of cow's milk as well as for an association between general milk fat consumption and the occurrence especially of breast, colorectal, and prostate tumors.
Whether the effects observed in epidemiological studies can be attributed to milk lipids or whether the promising preclinical data on their anti-cancer efficacy can be transferred to humans remains unclear at present, therefore this review summarizes the latest findings.
{"title":"Bovine milk fat and cancer risk: A double-edged sword?","authors":"Laura Elaine Strittmatter , Alban Piotrowsky , Luigi Marongiu , Sascha Venturelli , Christian Leischner","doi":"10.1016/j.jnutbio.2025.110233","DOIUrl":"10.1016/j.jnutbio.2025.110233","url":null,"abstract":"<div><div>Among the many macro- and micronutrients contained in cow's milk, one of the most important is the lipid fraction. While the nutritional and physiological benefits of milk consumption after the first years of life are the subject of some debate, there also appear to be conflicting views on the health aspects of the milk lipids, including their involvement in cancer.</div><div>Positive <em>in vitro</em> and/or <em>in vivo</em> data on growth-inhibiting or cytotoxic effects are available for lipid components of milk such as sphingomyelins and their degradation products or various hydroxy fatty acids. Isomers of linoleic acid and branched-chain fatty acids have also been shown to have anticarcinogenic potential in animal models by inducing apoptosis.</div><div>On the other hand, there is evidence of an association between increased cancer mortality and the consumption of high-fat milk, which contradicts the tumor-protecting effects observed <em>in vitro</em> and <em>in vivo</em>. Consumption of high-fat dairy products appears to be associated with an increased risk of developing types of cancer compared to low-fat dairy or other topical soy-based alternatives.</div><div>There are ambiguous results for an anticarcinogenic effect of various lipid constituents of cow's milk as well as for an association between general milk fat consumption and the occurrence especially of breast, colorectal, and prostate tumors.</div><div>Whether the effects observed in epidemiological studies can be attributed to milk lipids or whether the promising preclinical data on their anti-cancer efficacy can be transferred to humans remains unclear at present, therefore this review summarizes the latest findings.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110233"},"PeriodicalIF":4.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751892","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}
Pub Date : 2025-12-11DOI: 10.1016/j.jnutbio.2025.110232
Jiayue Su , Chenran Cai , Ying Zhang , Donglan Wang , Sijia Yan , Xueqiong Yao
Gestational diabetes mellitus (GDM) is a prevalent complication, affecting approximately 14% of pregnancies worldwide, and is associated with an elevated risk of both maternal and infant complications. It also exerts long-term adverse effects on offspring health, including metabolic, cardiovascular, and neurodevelopmental disorders, thereby compromising maternal and infant well-being. During pregnancy, an imbalance between folic acid and vitamin B12 has been linked to an increased risk of GDM and unfavorable metabolic outcomes in offspring, underscoring the potential clinical value of maintaining their balance and implementing early interventions. This review summarizes the role of folic acid and vitamin B12 in gestational diabetes and offspring development, aiming to bridge the gap between mechanistic insights and clinical evidence. It highlights the potential for reverse causality in linking vitamin B12-folic acid imbalance to GDM risk and underscores the need to integrate novel metabolic and epigenetic concepts into future intervention trials.
{"title":"The role of folic acid and vitamin B12 in gestational diabetes mellitus and offspring development: A narrative review","authors":"Jiayue Su , Chenran Cai , Ying Zhang , Donglan Wang , Sijia Yan , Xueqiong Yao","doi":"10.1016/j.jnutbio.2025.110232","DOIUrl":"10.1016/j.jnutbio.2025.110232","url":null,"abstract":"<div><div>Gestational diabetes mellitus (GDM) is a prevalent complication, affecting approximately 14% of pregnancies worldwide, and is associated with an elevated risk of both maternal and infant complications. It also exerts long-term adverse effects on offspring health, including metabolic, cardiovascular, and neurodevelopmental disorders, thereby compromising maternal and infant well-being. During pregnancy, an imbalance between folic acid and vitamin B12 has been linked to an increased risk of GDM and unfavorable metabolic outcomes in offspring, underscoring the potential clinical value of maintaining their balance and implementing early interventions. This review summarizes the role of folic acid and vitamin B12 in gestational diabetes and offspring development, aiming to bridge the gap between mechanistic insights and clinical evidence. It highlights the potential for reverse causality in linking vitamin B12-folic acid imbalance to GDM risk and underscores the need to integrate novel metabolic and epigenetic concepts into future intervention trials.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110232"},"PeriodicalIF":4.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751816","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}
Pub Date : 2025-12-06DOI: 10.1016/j.jnutbio.2025.110211
Zhen-xiao Ma , Ze-qun Yin , Zi-an Feng , Xiang-peng Xie , Ao Li , Shi-hao Fu , Qi Yue , Sheng Wang , Li-kun Ma , Ya-jun Duan , Dan-qing He , Jun-fang Wu , Shuang Zhang , Zhi-wei Zhao
Aortic aneurysm and dissection (AAD) is a life-threatening cardiovascular disorder with no currently available targeted therapies, underscoring the critical need for effective preventive strategies. Through integrative analysis of the UK Biobank and FooDB databases, we identified chlorogenic acid (CGA)––a natural polyphenol abundant in coffee and tea––as a potential protective compound against AAD. Using two mouse models of AAD: β-aminopropionitrile (BAPN) plus angiotensin II (Ang II) in 4-week-old wild-type mice and erythropoietin (EPO)-induced AAD in 8-week-old wild-type mice, we demonstrated that CGA administration significantly reduced AAD incidence, mortality, and aortic wall damage. Mechanistically, we discovered that the large neutral amino acid transporter 3 (LAT3) plays a pivotal role in AAD pathogenesis by mediating excessive branched-chain amino acids (BCAAs) uptake into vascular smooth muscle cells (SMCs). Dysregulated BCAAs metabolism led to intracellular BCAAs accumulation and hyperactivation of the mTOR signaling pathway, driving SMCs reprogramming and promoting AAD development. Crucially, CGA directly targeted and inhibited LAT3, thereby normalizing BCAA metabolism and suppressing mTOR activity, which mitigated AAD progression. Our findings not only reveal the therapeutic potential of CGA in AAD prevention but also identify the LAT3/BCAA/mTOR axis as a novel mechanistic target for AAD intervention.
{"title":"Food-derived chlorogenic acid prevents aortic aneurysm and dissection by nutritional restore branched-chain amino acid dyshomeostasis","authors":"Zhen-xiao Ma , Ze-qun Yin , Zi-an Feng , Xiang-peng Xie , Ao Li , Shi-hao Fu , Qi Yue , Sheng Wang , Li-kun Ma , Ya-jun Duan , Dan-qing He , Jun-fang Wu , Shuang Zhang , Zhi-wei Zhao","doi":"10.1016/j.jnutbio.2025.110211","DOIUrl":"10.1016/j.jnutbio.2025.110211","url":null,"abstract":"<div><div>Aortic aneurysm and dissection (AAD) is a life-threatening cardiovascular disorder with no currently available targeted therapies, underscoring the critical need for effective preventive strategies. Through integrative analysis of the UK Biobank and FooDB databases, we identified chlorogenic acid (CGA)––a natural polyphenol abundant in coffee and tea––as a potential protective compound against AAD. Using two mouse models of AAD: β-aminopropionitrile (BAPN) plus angiotensin II (Ang II) in 4-week-old wild-type mice and erythropoietin (EPO)-induced AAD in 8-week-old wild-type mice, we demonstrated that CGA administration significantly reduced AAD incidence, mortality, and aortic wall damage. Mechanistically, we discovered that the large neutral amino acid transporter 3 (LAT3) plays a pivotal role in AAD pathogenesis by mediating excessive branched-chain amino acids (BCAAs) uptake into vascular smooth muscle cells (SMCs). Dysregulated BCAAs metabolism led to intracellular BCAAs accumulation and hyperactivation of the mTOR signaling pathway, driving SMCs reprogramming and promoting AAD development. Crucially, CGA directly targeted and inhibited LAT3, thereby normalizing BCAA metabolism and suppressing mTOR activity, which mitigated AAD progression. Our findings not only reveal the therapeutic potential of CGA in AAD prevention but also identify the LAT3/BCAA/mTOR axis as a novel mechanistic target for AAD intervention.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110211"},"PeriodicalIF":4.9,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708324","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}
Pub Date : 2025-12-06DOI: 10.1016/j.jnutbio.2025.110227
Zou-Han Lin , Pin-I Chou , Jia-Wei Chang , Zong-Chen Lin , Yuan-Ting Sun , Ming-Hui Chang , Shih-En Huang , Yu-Min Yeh , Chien-Chin Chen , I-Chen Peng
Dysregulated lipid metabolism in hepatocytes heightens the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Fatty acid synthase (FAS), one of the key enzymes regulating lipid production in the liver, is upregulated in MASLD patients, making it a prime target for treatment. However, the regulatory mechanisms governing FAS expression and its post-translational modification in MASLD, as well as their potential contribution to hepatic inflammation, remain incompletely understood. In this study, we find that ten-eleven translocation 2 (TET2), thymine DNA glycosylase (TDG), FAS, and glutamine synthetase (GS) are upregulated in lipid mixture- or high-fat diet-induced hepatic steatosis, both in vitro and in vivo. The lipid mixture increases FAS and GS expression through TDG-mediated promoter demethylation. It also promotes hepatic lipid droplet accumulation and inflammation through TDG, FAS, and GS. Additionally, GS is essential for lipid mixture-induced O-linked N-acetylglucosaminylation (O-GlcNAcylation) of FAS, which enhances its stability in hepatocytes. These findings demonstrate that upregulation of FAS through TDG-mediated promoter demethylation and GS-mediated O-GlcNAcylation accelerates hepatic steatosis and inflammation in MASLD, providing mechanistic insights and highlighting these regulatory pathways as potential targets for therapeutic intervention.
肝细胞脂质代谢失调会增加代谢功能障碍相关脂肪变性肝病（MASLD）的风险。脂肪酸合成酶（FAS）是调节肝脏脂质生成的关键酶之一，在MASLD患者中上调，使其成为治疗的主要靶点。然而，FAS表达的调控机制及其在MASLD中的翻译后修饰，以及它们对肝脏炎症的潜在贡献，仍然不完全清楚。在这项研究中，我们发现在体外和体内，10 - 11易位2 （TET2）、胸腺嘧啶DNA糖基化酶（TDG）、FAS和谷氨酰胺合成酶（GS）在脂质混合物或高脂肪饮食诱导的肝脂肪变性中上调。脂质混合物通过tdg介导的启动子去甲基化增加FAS和GS的表达。它还通过TDG、FAS和GS促进肝脂滴积聚和炎症。此外，GS对于脂质混合物诱导的FAS的O-linked n -乙酰氨基葡萄糖酰化（o - glcnac酰化）至关重要，这增强了其在肝细胞中的稳定性。这些发现表明，通过tdg介导的启动子去甲基化和gs介导的o - glcn酰化，FAS的上调加速了MASLD的肝脂肪变性和炎症，提供了机制上的认识，并突出了这些调节途径作为治疗干预的潜在靶点。
{"title":"Promoter demethylation and protein O-GlcNAcylation-mediated enhancement of fatty acid synthase contributes to hepatic steatosis and inflammation in MASLD","authors":"Zou-Han Lin , Pin-I Chou , Jia-Wei Chang , Zong-Chen Lin , Yuan-Ting Sun , Ming-Hui Chang , Shih-En Huang , Yu-Min Yeh , Chien-Chin Chen , I-Chen Peng","doi":"10.1016/j.jnutbio.2025.110227","DOIUrl":"10.1016/j.jnutbio.2025.110227","url":null,"abstract":"<div><div>Dysregulated lipid metabolism in hepatocytes heightens the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Fatty acid synthase (FAS), one of the key enzymes regulating lipid production in the liver, is upregulated in MASLD patients, making it a prime target for treatment. However, the regulatory mechanisms governing FAS expression and its post-translational modification in MASLD, as well as their potential contribution to hepatic inflammation, remain incompletely understood. In this study, we find that ten-eleven translocation 2 (TET2), thymine DNA glycosylase (TDG), FAS, and glutamine synthetase (GS) are upregulated in lipid mixture- or high-fat diet-induced hepatic steatosis, both <em>in vitro</em> and <em>in vivo</em>. The lipid mixture increases FAS and GS expression through TDG-mediated promoter demethylation. It also promotes hepatic lipid droplet accumulation and inflammation through TDG, FAS, and GS. Additionally, GS is essential for lipid mixture-induced O-linked N-acetylglucosaminylation (O-GlcNAcylation) of FAS, which enhances its stability in hepatocytes. These findings demonstrate that upregulation of FAS through TDG-mediated promoter demethylation and GS-mediated O-GlcNAcylation accelerates hepatic steatosis and inflammation in MASLD, providing mechanistic insights and highlighting these regulatory pathways as potential targets for therapeutic intervention.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110227"},"PeriodicalIF":4.9,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145708298","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}
Pub Date : 2025-12-04DOI: 10.1016/j.jnutbio.2025.110222
Mengjie Zhang , Ziyue Dou , Langlang Yang , Hongqian Wang , Beibei Tian , Shaocheng Hong , Qi Yang , Jian Lu , Xi Chen
Spermidine (SPD), a microbiota‑derived polyamine, exerts potent anti‑inflammatory effects in colitis. This study investigated how SPD mitigates dextran sulfate sodium (DSS)–induced ferroptosis and explored the association between gut microbiota composition and polyamine metabolites in patients with ulcerative colitis (UC). DSS‑induced UC models were established in mice and HT‑29 cells, followed by SPD treatment. RNA sequencing was used to profile transcriptomic changes in HT‑29 cells, and the effects of SPD on NCOA4 and Ferritin were evaluated both in vivo and in vitro. NCOA4 silencing was performed to clarify its role in SPD‑mediated protection against ferroptosis. Fecal polyamines and gut microbiota profiles from UC patients and healthy controls were analyzed using UHPLC‑MS/MS and 16S rRNA sequencing. SPD significantly alleviated DSS‑induced colitis. Gene set enrichment analysis (GSEA) of differentially expressed genes in HT‑29 cells highlighted iron‑metabolism pathways as prominently affected. SPD mitigated DSS‑induced ferroptosis in vitro and in vivo, likely by limiting NCOA4‑dependent ferritin turnover and maintaining iron balance. In UC patients, disturbances in fecal polyamine levels corresponded closely with shifts in gut microbial composition, with 27 genera showing significant correlations with polyamine metabolites. Together, these findings position SPD as a modulator of ferroptosis via the NCOA4–ferritin axis and point to a potential therapeutic avenue. In UC, disrupted polyamine metabolites are closely linked to microbial alterations, implicating microbe–polyamine interactions in disease pathogenesis.
{"title":"Ferroptosis inhibition by spermidine via the NCOA4/Ferritin axis and polyamine–microbiota dysbiosis in ulcerative colitis","authors":"Mengjie Zhang , Ziyue Dou , Langlang Yang , Hongqian Wang , Beibei Tian , Shaocheng Hong , Qi Yang , Jian Lu , Xi Chen","doi":"10.1016/j.jnutbio.2025.110222","DOIUrl":"10.1016/j.jnutbio.2025.110222","url":null,"abstract":"<div><div>Spermidine (SPD), a microbiota‑derived polyamine, exerts potent anti‑inflammatory effects in colitis. This study investigated how SPD mitigates dextran sulfate sodium (DSS)–induced ferroptosis and explored the association between gut microbiota composition and polyamine metabolites in patients with ulcerative colitis (UC). DSS‑induced UC models were established in mice and HT‑29 cells, followed by SPD treatment. RNA sequencing was used to profile transcriptomic changes in HT‑29 cells, and the effects of SPD on NCOA4 and Ferritin were evaluated both <em>in vivo</em> and <em>in vitro</em>. NCOA4 silencing was performed to clarify its role in SPD‑mediated protection against ferroptosis. Fecal polyamines and gut microbiota profiles from UC patients and healthy controls were analyzed using UHPLC‑MS/MS and 16S rRNA sequencing. SPD significantly alleviated DSS‑induced colitis. Gene set enrichment analysis (GSEA) of differentially expressed genes in HT‑29 cells highlighted iron‑metabolism pathways as prominently affected. SPD mitigated DSS‑induced ferroptosis <em>in vitro</em> and <em>in vivo</em>, likely by limiting NCOA4‑dependent ferritin turnover and maintaining iron balance. In UC patients, disturbances in fecal polyamine levels corresponded closely with shifts in gut microbial composition, with 27 genera showing significant correlations with polyamine metabolites. Together, these findings position SPD as a modulator of ferroptosis via the NCOA4–ferritin axis and point to a potential therapeutic avenue. In UC, disrupted polyamine metabolites are closely linked to microbial alterations, implicating microbe–polyamine interactions in disease pathogenesis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110222"},"PeriodicalIF":4.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695817","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}
Pub Date : 2025-12-04DOI: 10.1016/j.jnutbio.2025.110224
Hai-Tao Yu , Lu-Tong Yang , Miao Yu , Yi-Ru Chen , Song Ni , Mo-Tong Liu , Wen-Hui Xu , Lin Xie
Nucleotides play a crucial role in the growth and development of infants. Studying the dynamics of nucleotides variation in human milk and the influencing factors can provide insights to guide the diets of lactating mothers. The colostrum milk (CM, 0–5 d), transitional milk (TM, 10–15 d), and mature milk (MM1, 40–45 d) were collected as longitudinal study. Additionally, late term mature milk (MM2, 200–240 d; MM3, 300–400 d) were collected as the cross-sectional study. The human milk free nucleotides, including cytidine monophosphate (CMP), uridine monophosphate (UMP), guanosine monophosphate (GMP), and adenosine monophosphate (AMP), were assessed using High Performance Liquid Chromatography (HPLC), and the total potentially available nucleosides (TPAN) were calculated. The food frequency questionnaire (FFQ) was used to investigate the types and quantities of food consumed by lactating mothers. Principal component analysis (PCA) was then employed to identify their dietary patterns. The interaction of dietary patterns and lactation time on the levels of nucleotides was analyzed by factorial analysis. The levels of nucleotides in breast milk varied throughout the period of lactation. GMP and AMP decreased over time, while UMP, CMP, and TPAN decreased in the TM stage and then increased in the MM1 stage. Factorial analysis showed that lactation time affected all human milk nucleotides and an interaction of lactation time and dietary pattern could be observed on GMP and AMP. Further analysis indicated that dietary patterns influenced nucleotides during the late term mature milk stages (MM2 and MM3), while nucleotides in CM were not influenced by diet. Mothers who consumed the Beans-Nuts dietary pattern exhibited the highest nucleotides in their mature milk, followed by those who consumed the Potato-Vegetable dietary pattern. The levels of nucleotides in human milk are influenced by both the stage of lactation and maternal dietary patterns.
{"title":"Effect of lactation time and dietary patterns on human milk nucleotides: A longitudinal and cross-sectional study","authors":"Hai-Tao Yu , Lu-Tong Yang , Miao Yu , Yi-Ru Chen , Song Ni , Mo-Tong Liu , Wen-Hui Xu , Lin Xie","doi":"10.1016/j.jnutbio.2025.110224","DOIUrl":"10.1016/j.jnutbio.2025.110224","url":null,"abstract":"<div><div>Nucleotides play a crucial role in the growth and development of infants. Studying the dynamics of nucleotides variation in human milk and the influencing factors can provide insights to guide the diets of lactating mothers. The colostrum milk (CM, 0–5 d), transitional milk (TM, 10–15 d), and mature milk (MM1, 40–45 d) were collected as longitudinal study. Additionally, late term mature milk (MM2, 200–240 d; MM3, 300–400 d) were collected as the cross-sectional study. The human milk free nucleotides, including cytidine monophosphate (CMP), uridine monophosphate (UMP), guanosine monophosphate (GMP), and adenosine monophosphate (AMP), were assessed using High Performance Liquid Chromatography (HPLC), and the total potentially available nucleosides (TPAN) were calculated. The food frequency questionnaire (FFQ) was used to investigate the types and quantities of food consumed by lactating mothers. Principal component analysis (PCA) was then employed to identify their dietary patterns. The interaction of dietary patterns and lactation time on the levels of nucleotides was analyzed by factorial analysis. The levels of nucleotides in breast milk varied throughout the period of lactation. GMP and AMP decreased over time, while UMP, CMP, and TPAN decreased in the TM stage and then increased in the MM1 stage. Factorial analysis showed that lactation time affected all human milk nucleotides and an interaction of lactation time and dietary pattern could be observed on GMP and AMP. Further analysis indicated that dietary patterns influenced nucleotides during the late term mature milk stages (MM2 and MM3), while nucleotides in CM were not influenced by diet. Mothers who consumed the Beans-Nuts dietary pattern exhibited the highest nucleotides in their mature milk, followed by those who consumed the Potato-Vegetable dietary pattern. The levels of nucleotides in human milk are influenced by both the stage of lactation and maternal dietary patterns.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110224"},"PeriodicalIF":4.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695750","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}
Pub Date : 2025-12-04DOI: 10.1016/j.jnutbio.2025.110225
Yuxin Shi , Jie Peng
Acute pancreatitis (AP) is a self-limiting inflammatory disorder, but severe cases can lead to persistent organ failure with high mortality. Metabolic dysregulation and inflammatory activation play critical roles in AP pathogenesis, highlighting the metabolic-inflammation crosstalk as a potential therapeutic target. Although riboflavin, an essential water-soluble vitamin, has been implicated in modulating disease processes, its role in AP remains unclear. In this study, untargeted metabolomics identified significant riboflavin downregulation in an AP mouse model. Subsequent in vivo experiments demonstrated that riboflavin intervention (25, 50, and 100 mg/kg) ameliorated pancreatic injury and systemic inflammation, with 50 mg/kg exhibiting optimal efficacy. Targeted metabolomics revealed elevated acetate levels following riboflavin supplementation. At the same time, transcriptomic and molecular biology assays showed riboflavin-mediated downregulation of HDAC3, a key acetate downstream target, and suppression of NF-κB pathway activation. In vitro, riboflavin and acetate mitigated pancreatic acinar cell damage, including apoptosis and necrosis, and inhibited NF-κB signaling. Rescue experiments using the HDAC3 inhibitor RGFP966 further provided pharmacological evidence for a mechanistic link between the acetate-HDAC3 axis and riboflavin’s protective effects. Collectively, these findings reveal that riboflavin alleviates AP, and its effect is associated with the modulation of the acetate-HDAC3 axis, offering a novel therapeutic strategy for this condition.
{"title":"Metabolomics identifies riboflavin as a therapeutic agent for acute pancreatitis","authors":"Yuxin Shi , Jie Peng","doi":"10.1016/j.jnutbio.2025.110225","DOIUrl":"10.1016/j.jnutbio.2025.110225","url":null,"abstract":"<div><div>Acute pancreatitis (AP) is a self-limiting inflammatory disorder, but severe cases can lead to persistent organ failure with high mortality. Metabolic dysregulation and inflammatory activation play critical roles in AP pathogenesis, highlighting the metabolic-inflammation crosstalk as a potential therapeutic target. Although riboflavin, an essential water-soluble vitamin, has been implicated in modulating disease processes, its role in AP remains unclear. In this study, untargeted metabolomics identified significant riboflavin downregulation in an AP mouse model. Subsequent <em>in vivo</em> experiments demonstrated that riboflavin intervention (25, 50, and 100 mg/kg) ameliorated pancreatic injury and systemic inflammation, with 50 mg/kg exhibiting optimal efficacy. Targeted metabolomics revealed elevated acetate levels following riboflavin supplementation. At the same time, transcriptomic and molecular biology assays showed riboflavin-mediated downregulation of HDAC3, a key acetate downstream target, and suppression of NF-κB pathway activation. <em>In vitro</em>, riboflavin and acetate mitigated pancreatic acinar cell damage, including apoptosis and necrosis, and inhibited NF-κB signaling. Rescue experiments using the HDAC3 inhibitor RGFP966 further provided pharmacological evidence for a mechanistic link between the acetate-HDAC3 axis and riboflavin’s protective effects. Collectively, these findings reveal that riboflavin alleviates AP, and its effect is associated with the modulation of the acetate-HDAC3 axis, offering a novel therapeutic strategy for this condition.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110225"},"PeriodicalIF":4.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695777","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}
The mammary gland undergoes continuous growth, differentiation, and cyclical remodeling throughout the whole life, with morphogenesis from the embryonic stage to adulthood being crucial and highly sensitive to nutritional supply. While moderate nutritional restriction in early life and subsequent restore can promote the tissues development such as muscle, its effects on the mammary remain largely unexplored and appear to depend critically on the development stage. Thus, the effects of moderated nutritional restriction in early life including embryonic (ER), suckling (SR), or pubertal (PR) periods on mammary development and subsequent lactation performance in mice were investigated in the present study. In this study, we imposed nutritional restriction on mice during either a single period or two periods. Mammary gland and serum samples were collected at maturity (56 d) and on lactation day 15 for hormonal, histological, and transcriptomic analyses. Our results demonstrate that ER enhances mammary development and adult lactation capacity by boosting proliferative activity and increasing the mammary stem cell content. In contrast, postnatal nutritional restrictions (SR and PR) disrupt normal gland morphogenesis by attenuating hormonal signaling responses and reducing stromal tissue remodeling. Notably, the adverse effects of SR on mammary morphology are reversible upon nutritional repletion, with no subsequent impact on milk production, whereas PR leads to a significant impairment in adult lactation. These findings reveal distinct regulatory mechanisms of nutritional intervention at various development stages and provide a foundational basis for optimizing lactational outcomes through targeted nutritional strategies.
{"title":"Pre-but not post-natal nutritional restriction promotes mammary development","authors":"Xusheng Dong, Qiuling Hou, Yingyu Mu, Xueyan Lin, Zhiyong Hu, Yun Wang, Yizhao Shen, Zhonghua Wang","doi":"10.1016/j.jnutbio.2025.110226","DOIUrl":"10.1016/j.jnutbio.2025.110226","url":null,"abstract":"<div><div>The mammary gland undergoes continuous growth, differentiation, and cyclical remodeling throughout the whole life, with morphogenesis from the embryonic stage to adulthood being crucial and highly sensitive to nutritional supply. While moderate nutritional restriction in early life and subsequent restore can promote the tissues development such as muscle, its effects on the mammary remain largely unexplored and appear to depend critically on the development stage. Thus, the effects of moderated nutritional restriction in early life including embryonic (ER), suckling (SR), or pubertal (PR) periods on mammary development and subsequent lactation performance in mice were investigated in the present study. In this study, we imposed nutritional restriction on mice during either a single period or two periods. Mammary gland and serum samples were collected at maturity (56 d) and on lactation day 15 for hormonal, histological, and transcriptomic analyses. Our results demonstrate that ER enhances mammary development and adult lactation capacity by boosting proliferative activity and increasing the mammary stem cell content. In contrast, postnatal nutritional restrictions (SR and PR) disrupt normal gland morphogenesis by attenuating hormonal signaling responses and reducing stromal tissue remodeling. Notably, the adverse effects of SR on mammary morphology are reversible upon nutritional repletion, with no subsequent impact on milk production, whereas PR leads to a significant impairment in adult lactation. These findings reveal distinct regulatory mechanisms of nutritional intervention at various development stages and provide a foundational basis for optimizing lactational outcomes through targeted nutritional strategies.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110226"},"PeriodicalIF":4.9,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695841","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}
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