Journal of Nutritional Biochemistry最新文献

{"title":"Gut microbiome, a potential modulator of neuroepigenome","authors":"Ruili Yang,&nbsp;Yi Xu,&nbsp;Feng Zhu,&nbsp;Xiaojing Ma,&nbsp;Tingting Fan,&nbsp;Hui-Li Wang","doi":"10.1016/j.jnutbio.2025.109961","DOIUrl":"10.1016/j.jnutbio.2025.109961","url":null,"abstract":"<div><div>Gut microbiome has a considerable impact on the central nervous system via the “gut-brain axis.” Neuroepigenome emerges as the interface between environment and genes, potentially help conveying the signals derived from the microbiome to the brain tissue. While only a limited number of studies have implicated epigenetic roles in the gut-brain axis, this review explores how gut microbiome might impact various brain-based epigenetic mechanisms, including DNA methylation, histone modification, ncRNA and RNA methylation, notably in the context of the specific neural complications. Among the epigenetic mechanisms, histone acetylation was most well-studied with respect to its relationships with gut microbiome, exerting a dynamic influence on gene expression in the brain. Furthermore, the pathways connecting gut bacteria to neuroepigenome were summarized, highlighting the roles of metabolites such as butyrate, propionate, acetate, lactate, and folate. Of particular interest, the roles of butyrate are emphasized due to their outstanding inhibitory activity towards histone deacetylases (HDACs), among other mechanisms. It is worth noting that some indirect gut-brain pathways may also be associated with the interplay between microbiome and neuroepigenome, while IL-6 has been found to effectively transmit microbe-derived signals to histone methylation in brains. Finally, we recapitulate the future perspectives critical to understanding this gut-brain crosstalk, such as clarifying the cause-and-effect relationship, bacterial cross-feeding within the gut, and the mechanisms underlying the site-specific histone modification in the brain. Together, this review attempts to consolidate our current knowledge about the “microbiome-neuroepigenome interplay” and propose a conceptual pathway to decipher the gut-brain axis in various neurological conditions.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"144 ","pages":"Article 109961"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142761","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":"Dietary addition of fraxetin improved intestinal structure and growth performance in juvenile grass carp (Ctenopharyngodon idella): As a potential novel phytogenic feed additive","authors":"Jie Zhang ,&nbsp;Wei-Dan Jiang ,&nbsp;Pei Wu ,&nbsp;Yang Liu ,&nbsp;Yao-Bin Ma ,&nbsp;He-Qun Shi ,&nbsp;Sheng-Yao Kuang ,&nbsp;Shu-Wei Li ,&nbsp;Ling Tang ,&nbsp;Xiao-Qiu Zhou ,&nbsp;Lin Feng","doi":"10.1016/j.jnutbio.2025.109969","DOIUrl":"10.1016/j.jnutbio.2025.109969","url":null,"abstract":"<div><div>The well-being and development of fish are affected to varying degrees under the intensive aquaculture model, and the use of Chinese herbs for aquaculture disease control and feed additives has received increasing attention. This study examined fraxetin supplementation in juvenile grass carp to investigate its effects on growth and intestinal structure. There were 1080 grass carp (11.58±0.01 g) assigned to 6 treatments, fed with fraxetin (0, 3.9, 7.9, 15.8, 31.5, and 63.1 mg/kg) for 60 d in each treatment. In our study, appropriate fraxetin significantly increased final body weight (FBW), percent weight gain (PWG), and specific growth rate (SGR) compared to the unadded group (<em>P&lt;.05</em>), but did not affect feed efficiency (FE) (<em>P&gt;.05</em>). The administration of 7.9 mg/kg of fraxetin significantly improved fish intestinal development and body composition. Appropriate dietary fraxetin significantly enhanced intestinal digestive enzymes and brush border enzyme activity (<em>P&lt;.05</em>), decreased serum diamine oxidase (DAO) levels (<em>P&lt;.05</em>), and decreased intestinal cell apoptosis (<em>P&lt;.05</em>). Appropriate levels of fraxetin inhibited the RhoA/ROCK signaling pathway while upregulating both mRNA and protein expression of tight junction (TJ) and adherens junction (AJ) (<em>P&lt;.05</em>). These changes significantly improved apical junction complex (AJC) integrity. In conclusion, dietary supplementation with appropriate levels of fraxetin added to the diets had a facilitating effect on digestion and absorption, improved intestinal structure, and promoted fish growth performance in juvenile grass carp. In addition, the optimal dietary fraxetin levels were evaluated to be 6.06 and 7.79 mg/kg based on linear regression analysis of PWG and DAO, respectively.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"144 ","pages":"Article 109969"},"PeriodicalIF":4.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142760","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":"Impact of fish oil supplement on brain lipids profile in ApoE-/- mice and C57BL/6 J mice treated with diets containing different dosage of vitamin E","authors":"Lu Liu ,&nbsp;Xiaochen Huang ,&nbsp;Jingjing Xu ,&nbsp;Xixiang Wang ,&nbsp;Yu Liu ,&nbsp;Xiuwen Ren ,&nbsp;Chi Zhang ,&nbsp;Ying Wang ,&nbsp;Yueyong Wang ,&nbsp;Shaobo Zhou ,&nbsp;Linhong Yuan","doi":"10.1016/j.jnutbio.2025.109964","DOIUrl":"10.1016/j.jnutbio.2025.109964","url":null,"abstract":"<div><div>The study was designed to explore the impact of fish oil supplement on the brain lipids profile in ApoE-deficient (ApoE-/-) mice and wild-type C57BL/6 J (C57 wt) mice treated with diets containing varying dosage of vitamin E (VE). Compared to C57 wt mice, ApoE-/- mice exhibited increased cortical TC and LDL-C levels, but decreased HDL-C level (<em>P</em>&lt;.05). The fish oil intervention, combined with low dietary VE intake resulted in increased cortical protein expression of CD36 and PPARγ in C57 wt mice. PI (36:5) was identified as a significantly different metabolite when compared to the control group in both C57 wt and ApoE-/- mice. The combination of fish oil and varying doses of VE had different effects on the expression of brain lipids and fatty acid transporters in ApoE-/- and C57 wt mice, indicating that ApoE status and dietary VE intake influence the responses of the cerebral lipids profile to fish oil supplementation.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"144 ","pages":"Article 109964"},"PeriodicalIF":4.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132143","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":"n-3 polyunsaturated fatty acids-enriched fish oil attenuates chronic alcohol-induced liver injury via a mechanism involving the upregulation of Retsat","authors":"Yuxuan Zhang ,&nbsp;Kaixin Pan ,&nbsp;Angcheng Xu ,&nbsp;Shuzhen Sun ,&nbsp;Qingling Huang ,&nbsp;Yicheng Wang ,&nbsp;Hao Wang ,&nbsp;Qiang Han ,&nbsp;Duo Li ,&nbsp;Qinchao Ding ,&nbsp;Jiaomei Li","doi":"10.1016/j.jnutbio.2025.109971","DOIUrl":"10.1016/j.jnutbio.2025.109971","url":null,"abstract":"<div><div>This study aimed to delineate the protective role of fish oil against alcoholic liver disease (ALD), identify the principal active component between eicosapentaenoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3), and elucidate the molecular mechanisms. C57BL/6J mice were randomly assigned to receive either an alcohol-fed (AF) or pair-fed control (PF) diet, enriched with fish oil (FO) or corn oil (CO) for four weeks. Additionally, a series of <em>in vitro</em> experiments were performed using AML-12 cells to further investigate potential mechanisms. The results showed that plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly lower in the AF-FO group compared to the AF-CO group, indicating that fish oil alleviated alcohol-induced liver damage. Hepatic antioxidant markers, including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were also higher in the AF-FO group than in the AF-CO group. Transcriptomic analysis revealed FO supplementation significantly affected genes involved in oxidoreductase activity and lipid metabolism pathways, with <em>Retsat</em> being the most up-regulated gene. The <em>in vitro</em> experiments indicated that DHA, but not EPA, markedly increased <em>Retsat</em> expression, cell viability, and the expression of genes related to oxidoreductase activity and lipid metabolism, compared to linoleic acid (LA, C18:2 n-6). Notably, knocking down <em>Retsat</em> abolished the protective effects of DHA. In conclusion, dietary fish oil mitigated chronic alcohol-induced liver injury primarily through DHA by upregulating <em>Retsat</em> and downstream genes associated with oxidoreductase function and lipid metabolism.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"144 ","pages":"Article 109971"},"PeriodicalIF":4.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132426","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":"1,25(OH)2D3 protected against LPS-induced acute lung injury through modulation of gut microbiota","authors":"Xiaoming Zhang ,&nbsp;Ye Li ,&nbsp;Yiting Gong ,&nbsp;Ning Jia ,&nbsp;Yuanqing Luo ,&nbsp;Jianrong Cao ,&nbsp;Yan Yuan ,&nbsp;Zitian Wang ,&nbsp;Xueyuan Zhi","doi":"10.1016/j.jnutbio.2025.109970","DOIUrl":"10.1016/j.jnutbio.2025.109970","url":null,"abstract":"<div><div>This study investigated whether gut and lung microbiota mediated the effects of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] against acute lung injury (ALI). We evaluated the impact of various 1,25(OH)₂D₃ doses on lipopolysaccharide (LPS)-induced ALI and characterized microbial changes in both intestinal and pulmonary communities. Correlation between lung and gut microbiota was assessed. To further explore the role of intestinal flora, a depletion model was established using antibiotics (ABX). Our results indicated that 1,25(OH)₂D₃ alleviated LPS-induced ALI, as evidenced by reduced pathological damage, downregulated expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α), increased levels of anti-inflammatory cytokine (IL-10), and suppressed TLR4/NF-κB and JNK pathways. LPS reduced α diversity and altered β diversity and composition of intestinal microbes, which were partially reversed by 1,25(OH)₂D₃ intervention. Notably, 1,25(OH)₂D₃ enhanced gut microbiota diversity and elevated the relative abundance of <em>Muribaculaceae</em> and <em>Lachnospiraceae</em> genus. Importantly, depletion of gut flora with ABX eliminated the anti-inflammatory effects of 1,25(OH)₂D₃, including its inhibition of LPS-induced cytokine expressions and pathway activation. Although LPS did not significantly affect the diversity of lung microbiota, it seemed to change its composition and induced a significant correlation between intestinal and pulmonary microbial communities, which was attenuated by 1,25(OH)₂D₃. In conclusion, our findings suggested that the protective effects of 1,25(OH)₂D₃ against LPS-induced ALI might be partially mediated by gut microbiota, highlighting a potential mechanism for vitamin D’s immunomodulatory activity in inflammatory lung disease.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"144 ","pages":"Article 109970"},"PeriodicalIF":4.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127984","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":"Intake of neutral core human milk oligosaccharides (HMOs) during early life improves long-term bone quality","authors":"N. Bonnet ,&nbsp;F.N. Schmidt ,&nbsp;M. Baruchet ,&nbsp;E. Migliavacca ,&nbsp;M. Ramos-Nieves ,&nbsp;L. Favre ,&nbsp;D. Brassart ,&nbsp;K. Mletzko ,&nbsp;B. Busse ,&nbsp;Sietse-Jan Koopmans ,&nbsp;M.N. Horcajada","doi":"10.1016/j.jnutbio.2025.109968","DOIUrl":"10.1016/j.jnutbio.2025.109968","url":null,"abstract":"<div><div>Infancy is a key period for bone growth, determining bone strength later in life. Studies have provided early insights into the role that human milk oligosaccharides (HMOs) may play in growth, potentially through their effects on the microbiome. However, focus was on sialylated HMOs whereas neutral core HMOs represent the most abundant class in human breast milk. We explored impact on bone quantity, quality and strength in 1year old female minipigs exposed to neutral HMOs during preweaning. Milk formula led to significant lower bone mineral density and quality compared to sow-fed (positive control). Milk formula enriched in neutral HMOs led to higher tibia bone density, structure and matrix quality compared to milk formula, leading to similar bone strength as in naturally sow-fed, whereas sialylated HMOs was not able to significantly differentiate than milk formulae. We identify a specific correlation between neutral HMOs, bone and microbiome, with the novel taxonomies <em>Turicibacter sanguinis</em> and <em>Paraprevotella clara</em> associating with HMO-mediated bone strength. This study provides important insights on the role of different HMO subtypes on bone health and possible associated adaptations in microbiome taxa, providing perspectives for new nutritional solutions for bone growth in early life.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"144 ","pages":"Article 109968"},"PeriodicalIF":4.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127987","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":"Associations of dietary fiber intake with all-cause and cardiovascular mortality among maintenance hemodialysis patients: a retrospective cohort study","authors":"Shuang Zhang ,&nbsp;Qi-Jun Wu ,&nbsp;Yu-Lin Wu ,&nbsp;Ping Xiao ,&nbsp;Zhi-Hong Wang ,&nbsp;Hong Liu ,&nbsp;Yan Lu ,&nbsp;Shu-Xin Liu","doi":"10.1016/j.jnutbio.2025.109966","DOIUrl":"10.1016/j.jnutbio.2025.109966","url":null,"abstract":"<div><div>To determine the association between dietary fiber intake (DFI) and all-cause mortality and cardiovascular mortality in Chinese maintenance hemodialysis (MHD) patients, considering fiber types and sources. Therefore, adjusted Cox regression analyses were utilized to assess the correlation between quartiles of DFI and mortality. Restricted cubic spline (RCS) regression was employed to investigate the nonlinear relationship between the total cereal fiber and mortality. Subgroup and sensitivity analysis was performed to examine the robustness. Among 742 patients (median follow-up: 30.47 months), 210 deaths (28.30%) occurred, including 149 (20.08%) cardiovascular-related deaths. Higher total cereal fiber intake correlated with reduced all-cause mortality [HR (hazard ratio) _{quartile 4 (Q4) vs. quartile 1 (Q1)}=0.58, 95% CI: 0.36–0.93] and cardiovascular mortality (HR _{Q4 vs. Q1}=0.53, 95% CI=0.30–0.95). Apart from fruit fiber as well as bean fiber for all-cause mortality and soluble fruit fiber for cardiovascular mortality, a similar association was observed for fiber from other dietary sources, albeit without statistical significance. Furthermore, each standard deviation increase in total cereal fiber intake lowered all-cause mortality risk (HR=0.82, 95% CI: 0.69–0.98). The findings were robust in all the subgroup and sensitivity analyses. Additionally, the RCS regression model indicated linear inverse associations between total cereal fiber and mortality risks (all <em>p</em> _nonlinear&gt;.05). In conclusion, total cereal fiber intake was inversely associated with reduced all-cause and cardiovascular mortality in MHD patients. Our data suggest that cereal fiber is a potentially protective component and may enhance overall longevity in MHD patients.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"144 ","pages":"Article 109966"},"PeriodicalIF":4.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119912","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":"Differences in mature human milk metabolic profiles based on delivery mode and parity","authors":"Jiayue Tang ,&nbsp;Cai Shen ,&nbsp;Dan Yao ,&nbsp;Jingwen Yu ,&nbsp;Yanan Liu ,&nbsp;Maolin Tu ,&nbsp;Hong Zhang ,&nbsp;Xuebing Xu ,&nbsp;Oi-Ming Lai ,&nbsp;Ling-Zhi Cheong","doi":"10.1016/j.jnutbio.2025.109967","DOIUrl":"10.1016/j.jnutbio.2025.109967","url":null,"abstract":"<div><div>Human milk (HM) is regarded as the gold standard for infant nutrition. The metabolite profiles of mature human milk (MHM) have been reported to be affected by maternal physiological conditions, lactation stage, and maternal diets. We collected MHM (3–6 months postpartum) from 32 healthy mothers with different parities and delivery modes. Then, GC-MS and LC-MS were used to perform an untargeted metabolomic study. A clear distinction can be observed in terms of MHM metabolites of mothers with different delivery modes and parities with a 95% confidence interval. A total of 119 differentially expressed metabolites (DEMs) were identified in MHM of women with different delivery modes. Metabolic pathway analyses indicated that these DEMs were mainly associated with fatty acid biosynthesis. The higher abundances of these DEMs in MHM of cesarean women may be due to the differing levels of cortisol and oxytocin between mothers with different delivery modes. Meanwhile, 284 DEMs were identified in MHM of women with different parities. These DEMs were primarily related to ABC transporters, center carbon metabolism in cancer, and D-amino acid metabolism. These findings highlighted the impact of delivery mode and parity on HM metabolite composition. Further research is needed to explore the long-term health implications of these metabolic differences and optimize infant nutrition strategies.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"144 ","pages":"Article 109967"},"PeriodicalIF":4.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119874","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":"Exploring the crosstalk between gut microbiota and stool metabolome in omnivorous, vegetarian, and vegan diets: A pilot study","authors":"Andrea Massaro ,&nbsp;Arianna Peruzzo ,&nbsp;Carmela Zacometti ,&nbsp;Mirella Zancato ,&nbsp;Roberto Piro ,&nbsp;Carmen Losasso ,&nbsp;Alessandra Tata ,&nbsp;Gregorio Peron","doi":"10.1016/j.jnutbio.2025.109965","DOIUrl":"10.1016/j.jnutbio.2025.109965","url":null,"abstract":"<div><div>Gut microbiota (GM) and fecal metabolome are shaped by different dietary regimens. Nevertheless, outlining generalized patterns is challenging, due to the intrinsic heterogeneity of individual dietary choices. In this work, the fecal metabolome of adult volunteers consuming omnivorous (n=44), vegetarian (n=29), and vegan diets (n=25) for at least 12 months was characterized. The crosstalk among diet, GM and fecal metabolome was also investigated correlating metabolomics and metataxonomics data. Untargeted metabolomic profiles were correlated with metataxonomics data previously acquired on the same stool samples. The sphingomyelin SM(d18:2/18:1-2OH) and phosphoethanolamines from animal-based food were associated to the omnivorous diet and were negatively correlated to beneficial <em>Bacteroides ovatus</em> and <em>Odoribacter</em> genus. Plant glycerides, sterols, triterpenes, and oleic-linoleic acid were associated with the vegan diet. Oleic-linoleic acid was positively correlated with <em>Alistipes putredinis</em>. Chenodeoxycholic acid, a primary bile acid, was identified as a marker of vegan diet, while ketolithocholic acid, a secondary bile acid, was associated to the omnivorous diet. This latter was also negatively correlated to <em>B.ovatus</em>.</div><div>Overall, results confirm that assessing markers of dietary regimens instead of specific food categories is challenging, especially if volunteers’ diet is not strictly monitored. However, the integration of metabolomics and metataxonomic data allows to better understand the effects of specific food components on the GM and represents a suitable approach for further molecular investigation in nutrition.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"144 ","pages":"Article 109965"},"PeriodicalIF":4.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119875","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":"Phenethyl Isothiocyanate (PEITC) interaction with Keap1 activates the Nrf2 pathway and inhibits lipid accumulation in adipocytes","authors":"Hae-Sun Ko ,&nbsp;Kwonyoung Kim ,&nbsp;Yu-Ran Na ,&nbsp;Chang-hwan Yeom ,&nbsp;Chu Won Nho ,&nbsp;Yoon Shin Cho ,&nbsp;Jihoe Kim ,&nbsp;Kye Won Park","doi":"10.1016/j.jnutbio.2025.109963","DOIUrl":"10.1016/j.jnutbio.2025.109963","url":null,"abstract":"<div><div>Phenethyl isothiocyanate (PEITC) has been recognized for its potential effects in various human diseases. However, the impact of PEITC on adipocyte differentiation and its underlying molecular mechanisms is not well understood. This study investigates the effects of PEITC on adipocyte differentiation and elucidates the molecular mechanisms involved in Nrf2 activation. The effects of PEITC on adipocyte differentiation were assessed in C3H10T1/2 and 3T3-L1 cells. Nrf2-induced effects by PEITC were examined in Nrf2 knockout (KO) MEF and Keap1 KO H1299 cells. The interaction between PEITC and Keap1 was evaluated using thermal shift assays and Co-immunoprecipitation experiments. Reconstitution of cysteine mutants of Keap1 in Keap1 KO cells was used to elucidate a critical amino acid for the PEITC-induced Nrf2 stabilization. The initial stages of adipogenesis were crucial for PEITC's antiadipogenic effects in C3H10T1/2 and 3T3-L1 cells. PEITC increased Nrf2 protein expression, but this induction was absent in Keap1 KO cells. Thermal shift assays with the purified BTB domain of Keap1 confirmed a direct interaction with PEITC. Re-expression of Keap1 in Keap1 KO cells showed that the cysteine residue at position 151 is essential for PEITC-induced Nrf2 expression and the disruption of the Nrf2-Keap1 complex. PEITC was found to activate Nrf2-mediated gene expression and inhibit adipocyte differentiation, at least partially, through Nrf2-dependent mechanisms. This study confirms the antiadipogenic effects of PEITC. Mechanistic investigations demonstrate that PEITC interacts with Keap1 and that the cysteine residue (C151) of Keap1 is critical for PEITC's effects on Nrf2 activation.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"144 ","pages":"Article 109963"},"PeriodicalIF":4.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094128","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}