Journal of Nutritional Biochemistry最新文献

{"title":"Strontium and barium in deciduous teeth and infant feeding methods: A birth cohort adjunct study to the Japan environment and children's study.","authors":"Aya Hisada, Yu-Ki Tanaka, Akifumi Eguchi, Midori Yamamoto, Kenichi Sakurai, Emiko Todaka, Noriyuki Suzuki, Yasumitsu Ogra, Atsushi Kasamatsu, Katsuhiro Uzawa, Chisato Mori","doi":"10.1016/j.jnutbio.2025.110035","DOIUrl":"10.1016/j.jnutbio.2025.110035","url":null,"abstract":"<p><p>Deciduous teeth are a unique medium that record exposure to various elements over time, as they are formed during fetal and infantile periods. We aimed to evaluate the association between infant feeding methods and changes in the distribution of Barium (Ba) and Strontium (Sr) in deciduous teeth of children. The current analysis included 216 children around 6-7 years of age whose deciduous central incisor teeth were provided between March 2018 and February 2020, as an adjunct study of the Japan Environment and Children's study. Ba, Sr, and Calcium (Ca) levels in the deciduous teeth of these children were measured using laser ablation-inductively coupled plasma-mass spectrometry. We estimated the association between feeding methods or season of birth and the Ba to Ca (Ba:Ca) and Sr to Ca (Sr:Ca) ratios using multivariable linear mixed effects models. The Ba:Ca and Sr:Ca ratios were higher in the formula feeding group than in the breastfeeding group during the postnatal period (Ba:Ca: β=0.242 [95% CI: 0.149-0.335], Sr:Ca: β=0.223 [95% CI: 0.160-0.287] for formula group) and prenatal period (Ba:Ca: β=0.145 [95% CI: 0.062-0.227], Sr:Ca: β=0.152 [95% CI: 0.093-0.210] for formula group). Furthermore, the Sr:Ca ratio tended to be higher for summer-born children than for winter-born ones. The Ba:Ca and Sr:Ca ratios in deciduous teeth can serve as useful biomarkers for estimating feeding methods. Deciduous central incisors may serve as useful indicators of longitudinal elemental exposure and nutritional status from the prenatal to postnatal periods.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110035"},"PeriodicalIF":4.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649751","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":"Vitamin D₃ supplementation ameliorates adipose tissue inflammation and adipocyte hypertrophy in type 2 diabetic mice through downregulation of RAGE and SREBP-1c.","authors":"Yoon-Ah Kim, Minha Oh, Sohee Jung, Deok Hoon Kwon, Ga Young Lee, Sung Nim Han","doi":"10.1016/j.jnutbio.2025.110037","DOIUrl":"10.1016/j.jnutbio.2025.110037","url":null,"abstract":"<p><p>Type 2 diabetes is characterized by chronic low-grade inflammation and insulin resistance resulting from activation and infiltration of immune cells into adipose tissue. Vitamin D reportedly exerts an anti-inflammatory effect by regulating immune cell activity and inflammatory cytokine production. This study aimed to investigate the effects of vitamin D supplementation on lymphoid and myeloid immune cell distribution in the adipose tissue and explore the mechanisms by which vitamin D modulates adipose tissue inflammation in diabetes. Five-week-old, male C57BLKS/J-m⁺/m⁺ (CON) and C57BLKS/J-db/db (DB) mice were fed diets containing either 1,000 or 10,000 IU vitamin D/kg diet for 8 weeks. Vitamin D supplementation resulted in a smaller weight gain (33.8% lower), less adipocyte hypertrophy (16.9% lower), and a lower fasting blood glucose concentration (7.4% lower) in DB group. Vitamin D supplementation did not inhibit macrophage and dendritic cell infiltration into adipose tissue; nonetheless, it reduced the percentage of CD8⁺ T cells (18% lower). In DB group, vitamin D supplementation downregulated the gene expression of interleukin 6 (Il6) and CC motif chemokine ligand 2 (Ccl2) in stromal vascular cells (28.2% and 17.3% lower, respectively) as well as that of Il6, Ccl2, sterol regulatory element-binding transcription factor 1 (Srebf1), and advanced glycosylation end product-specific receptor (Ager) in adipose tissue (42.8%, 24.9%, 33.1%, and 58.2% lower, respectively). In conclusion, vitamin D supplementation attenuated the inflammatory response and adipocyte hypertrophy in adipose tissue from diabetic mice. The inhibition of Ager and Srebf1 by vitamin D supplementation potentially contributes to vitamin D's anti-inflammatory and anti-adiposity effects in diabetic mice.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110037"},"PeriodicalIF":4.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667822","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":"Theaflavin-3,3'-digallate prevents alcoholic liver injury by suppressing hepatic TLR4/NF-κB signaling and modulating the gut-liver axis in mice.","authors":"Meng-Ge Tang, Li-Gui Xiong, Jian-An Huang, Yukihiko Hara, Sheng Zhang, Zhong-Hua Liu, Ai-Ling Liu","doi":"10.1016/j.jnutbio.2025.110031","DOIUrl":"10.1016/j.jnutbio.2025.110031","url":null,"abstract":"<p><p>Dietary intervention is crucial for the clinical management of alcoholic liver injury. As the primary bioactive component in fermented tea, theaflavin-3,3'-digallate (TF3) possesses potent antioxidative and anti-inflammatory capacities, but its protective mechanisms against alcoholic liver injury via the gut-liver axis require systematic elucidation. This study evaluated the protective effects and underlying mechanisms of high-purity TF3 (2.5/5/10 mg/kg, 12-week oral gavage) against alcoholic liver injury in C57BL/6 J mice. TF3 administration significantly reduced serum lipids, attenuated hepatic steatosis, and suppressed oxidative stress and pro-inflammatory cytokine production in alcohol-fed mice. Mechanistically, TF3 enhanced intestinal barrier integrity by upregulating tight junction proteins in the colon and ileum, increased beneficial microbiota like Lactobacillus and Bifidobacterium, and modulated microbial metabolites including short-chain fatty acids (SCFAs) and tryptophan. These changes reduced circulating lipopolysaccharide (LPS), suppressed hepatic toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activation, and ultimately ameliorated hepatic inflammation while enhancing oxidative stress regulation. This work reveals novel mechanisms of TF3 in preventing alcoholic liver injury, providing a theoretical foundation for dietary applications.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110031"},"PeriodicalIF":4.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642853","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":"Oxidative stress and caspase 3/Gsdme-dependent pyroptosis contributes to high fat diet induced-intestinal inflammation and lipotoxicity via Srebp1 cleavage at D444 site by caspase 3.","authors":"An-Gen Yu, Xiao-Lei Wei, Ester Zito, Hua Zheng, Chong-Chao Zhong, Yu-Long Gong, Zhi Luo","doi":"10.1016/j.jnutbio.2025.110033","DOIUrl":"10.1016/j.jnutbio.2025.110033","url":null,"abstract":"<p><p>Excessive dietary fat intake was associated with intestinal inflammation and lipotoxicity, but the underlying mechanism remained elusive. In this study, we investigated the effects and mechanisms of dietary fat addition on intestinal inflammation and lipid metabolism by using yellow catfish Pelteobagrus fulvidraco, a freshwater teleost fish of ecological and economic importance. Here, we found that high fat diet (HFD) and fatty acid (FA) incubation induced intestinal lipotoxicity and barrier damage, activated oxidative stress and induced intestinal inflammation by activating cysteinyl aspartate specific proteinase 3 (caspase 3)/ gasdermin E (Gsdme) -dependent pyroptosis; oxidative stress mediated FA-induced pyroptosis, lipogenic metabolism and lipid accumulation; high dietary fat induced full-length sterol regulatory element binding protein 1 (Srebp1) cleavage by caspase 3, which in turn produced the active cleaved forms of Srebp1, and accordingly contributed to lipogenic metabolism and lipid accumulation; D444 was identified as the cleavage site of Srebp1 by caspase 3. Mechanistically, overexpression of the cleaved Srebp1 (Flag-N-Srebp1) by caspase 3 increased the activities of the promoters of lipogenic genes (fatty acid synthase [fas], acetyl CoA carboxylase [acca] and stearoyl-CoA desaturase 1 [scd1]), thereby up-regulating lipogenic metabolism and inducing lipid accumulation. Thus, our study elucidated the novel mechanism of high fat diet (HFD) inducing inflammation and lipotoxicity, and found that oxidative stress and caspase 3/ GsdmE-dependent pyroptosis played important roles in these processes.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110033"},"PeriodicalIF":4.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649750","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":"Adequate selenium nutrition attenuated the association between cadmium and renal health in U.S. adults: evidence from NHANES data (2011-2018).","authors":"Junying Zhu, Shimiao Dai, Chenggang Yang, Ziyu Han, Zhan Shi, Yutian Luo, Alexey A Tinkov, Longjian Liu, Ji-Chang Zhou","doi":"10.1016/j.jnutbio.2025.110032","DOIUrl":"10.1016/j.jnutbio.2025.110032","url":null,"abstract":"<p><p>Cadmium (Cd) exposure is well-known to be hazardous to renal function. Although animal experiments suggest that selenium (Se) supplementation has beneficial effects on Cd-induced organ damage, epidemiological evidence on the mitigation of Se on Cd-induced renal damage is still insufficient. We used data from the National Health and Nutrition Examination Survey (NHANES) cycles from 2011 to 2018, and performed survey-weighted linear regression, logistic regression, and restricted cubic spline analyses to evaluate the associations of urine Cd (UCd), blood Cd (BCd), daily Se intake (DSe), and blood Se (BSe) with estimated glomerular filtration rate (eGFR), urine albumin creatinine ratio (UACR), and CKD risk, including the effects of DSe and BSe on the associations of UCd and BCd with renal health. In our study, UCd and BSe were positively associated with eGFR, but negatively associated with CKD risk. UCd and BCd were positively associated with UACR, and BCd was positively associated with CKD risk. No independent associations of DSe with eGFR, UACR, and CKD risk were observed. Additionally, we observed that the associations of Cd exposure with renal injury indicators and CKD risk were attenuated in participants with adequate DSe levels and/or higher BSe levels. Our findings suggested that Cd exposure was associated with renal impairment and CKD risk, and maintaining adequate DSe and good Se status attenuated the associations of Cd exposure with renal health. Further research is needed to evaluate the health effects of interactions between Se and Cd.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110032"},"PeriodicalIF":4.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649749","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":"Association of Poor Vitamin K Status with Inflammation and Gut Microbiota in Hemodialysis Patients: A Cross-Sectional Study.","authors":"Ligia Soares Lima, Marcia Ribeiro, Ludmila F M F Cardozo, Rudolf Bittner, Marcelo Ribeiro-Alves, Júnia Schultz, Alexandre Soares Rosado, Paulo Emilio Correa Leite, Lia S Nakao, Leon J Schurgers, Denise Mafra","doi":"10.1016/j.jnutbio.2025.110139","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110139","url":null,"abstract":"<p><strong>Background: </strong>Vitamin K insufficiency is common in chronic kidney disease (CKD) and may be associated with gut dysbiosis, which decreases the number of vitamin K-producing bacteria. This insufficient status worsens inflammation, leading to vascular calcification and oxidative stress.</p><p><strong>Objective: </strong>This study investigates the correlation between vitamin K status and gut microbiota composition, and its association with inflammation in hemodialysis (HD) patients.</p><p><strong>Methods: </strong>In this cross-sectional study, patients were grouped based on dephosphorylated-uncarboxylated matrix gla-protein (dp-ucMGP) levels: adequate (≤ 500 pmol/L) or inadequate (> 500 pmol/L) vitamin K status. Plasma cytokines were analyzed using a multiplex assay, and uremic toxins via reverse-phase high-performance liquid chromatography (RP-HPLC). Gut microbiota composition was assessed in a subgroup using fecal DNA extraction and 16S rRNA gene sequencing on the Illumina NovaSeq PE250 platform.</p><p><strong>Results: </strong>Among 107 patients (53 [interquartile range = 16] years and 36 [interquartile range = 42] months on HD) completed the study, 70 patients (53 years, BMI, 24.2Kg/m²) exhibited insufficient vitamin K status, and 37 patients presented adequate status (52.5 years, BMI, 25.6Kg/m²). Patients with inadequate vitamin K status exhibited significantly higher levels of interleukin (IL)-6, IL-1β, granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) compared to patients with adequate status, reflecting elevated inflammatory marker levels in patients with insufficient vitamin K. Additionally, Bacteroides, a key vitamin K2-producing genus, was decreased in patients with inadequate vitamin K status.</p><p><strong>Conclusions: </strong>Gut dysbiosis is a consequence of CKD, which can result in reduced production of vitamin K and subsequent insufficient status. Additionally, inadequate vitamin K status may contribute to the inflammatory state in patients undergoing HD.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110139"},"PeriodicalIF":4.9,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238847","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":"Investigating the relationship between dietary vitamin B12 and bone mineral density: observational and genetic analyses.","authors":"Yangdan Zhong, Rong Xiang, Xunying Zhao, Maoyao Xia, Yang Qu, Bowen Lei, Linna Sha, Tao Han, Xin Song, Bin Yang, Sirui Zheng, Ting Yu, Jinyu Zhou, Jiangbo Zhu, Qin Deng, Jiaojiao Hou, Xia Jiang","doi":"10.1016/j.jnutbio.2025.110134","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110134","url":null,"abstract":"<p><strong>Background: </strong>Although a potential relationship between dietary vitamin B12 (VB12) and heel estimated bone mineral density (eBMD) has been suggested, the detailed phenotypic and genetic associations that underpin this relationship remain unclear.</p><p><strong>Method: </strong>We first assessed the phenotypic association between dietary VB12 and eBMD using linear regression and restricted cubic splines based on data from the UK Biobank (N = 64,326). We then explored the genetic relationship between these traits through a large-scale genome-wide cross-trait analysis, leveraging summary statistics from the hitherto largest genome-wide association studies (N_{dietary VB12} = 51,453, N_eBMD = 426,824).</p><p><strong>Results: </strong>Observational analysis showed no linear association (β = -0.001, P = 0.63) but an inverted U-shaped relationship (P_non-linear = 0.045) of dietary VB12 with eBMD. While no overall genetic correlation was found between dietary VB12 and eBMD, two significant local genetic signals were detected at 13q32.3 and 15q26.1. Cross-trait meta-analysis identified seven pleiotropic single-nucleotide polymorphisms (SNPs) shared between dietary VB12 and eBMD, with two showing colocalization (PPH4 > 0.60). Transcriptome-wide association study revealed one shared gene-tissue pair enriched in Brain-Brodmann Area 9. Although no linear causal association was detected, non-linear Mendelian randomization unveiled a non-linear relationship between dietary VB12 and eBMD.</p><p><strong>Conclusion: </strong>Both phenotypic and genetic analyses suggest a non-linear association between dietary VB12 and eBMD. The shared genetic basis underlying these traits highlights common biological mechanisms, providing insights for future mechanistic research on nutritional prevention of osteoporosis.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110134"},"PeriodicalIF":4.9,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238910","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":"Validation of an ovine model for studying impacts of prenatal docosahexaenoic acid supplementation on fetal tissue membrane composition and metabolism.","authors":"Asma K Omar, Lance C Li Puma, Briana D Risk, Aria C Witt, Cheyanne S Izon, Luke A Whitcomb, Dorcas J Kareng, Quinton A Winger, Gerrit J Bouma, Adam J Chicco","doi":"10.1016/j.jnutbio.2025.110137","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110137","url":null,"abstract":"<p><p>Dietary supplementation with long-chain omega-3 fatty acids such as docosahexaenoic acid (DHA) is recommended to women during pregnancy to prevent pre-term birth and support optimal fetal development. DHA supplementation also decreases circulating triglyceride levels through diverse effects on systemic lipid metabolism, but its impacts on fetal metabolism are largely unknown due to inherent limitations of such investigations during pregnancy. The aim of the present study was to validate a large animal model suitable for investigating impacts of prenatal DHA supplementation on fetal development and metabolism. White-faced ewes were fed either a control diet (Show-rite NewCo Lamb Feed) or a DHA-supplemented diet (control diet + 3% algae-derived DHA) from 2-3 weeks before pregnancy until mid-gestation (75 days), after which serum, placenta and fetal tissues were collected for biochemical analysis of phospholipid fatty acid composition and fatty acid transporter expression, and a broader characterization of nutrient metabolism of fetal heart, skeletal muscle, and liver. Prenatal DHA supplementation reduced maternal serum triglycerides and significantly enriched all six fetal tissues examined. These results were paralleled by tissue-specific impacts on fetal fatty acid transporters and metabolism, a greater capacity of fetal muscle and heart to oxidize lipids over carbohydrate substrates, and reduced expression of insulin receptor substrate-1 in fetal muscle and liver. In conclusion, this study demonstrates the utility of an ovine model for investigating the biological effects of prenatal DHA supplementation on fetal development and metabolism, and highlights the need for a better understanding of its impacts on fetal and offspring metabolic health trajectory.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110137"},"PeriodicalIF":4.9,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238903","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":"D-Allulose Improves Mitochondrial Respiratory Function and Alleviates Obesity-Induced Liver Dysfunction: A Comparative Study with Erythritol in HFD-Fed Mice.","authors":"Su-Kyung Shin, Eun Ji Kim, Sung-Su Choi, JaeHyuck Lee, Eun-Young Kwon, Heekyong R Bae","doi":"10.1016/j.jnutbio.2025.110135","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110135","url":null,"abstract":"<p><p>This study investigated the anti-obesity and anti-inflammatory effects of D-Allulose compared to erythritol in high-fat diet (HFD)-fed mice, focusing on liver mitochondrial function. Both D-Allulose and erythritol significantly reduced body weight gain, white adipose tissue (WAT) weight, and plasma lipid levels. D-Allulose, especially at higher doses (H_AL), demonstrated superior effects, including reductions in visceral and total WAT weight, adipocyte size, and hepatic and WAT fibrosis, compared to erythritol. D-Allulose also significantly enhanced mitochondrial function, as shown by increased expression of genes and proteins related to lipolysis and oxidative phosphorylation, which were not observed in the erythritol group. Gene expression analysis revealed that D-Allulose more effectively restored HFD-altered gene expression, suggesting stronger regulation of obesity-induced metabolic and inflammatory processes. These findings highlight D-Allulose as a functional sweetener with superior anti-obesity and anti-inflammatory effects, primarily through improved mitochondrial function and modulation of immune and metabolic responses.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110135"},"PeriodicalIF":4.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232950","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 Mediate Hyodeoxycholic Acid-FXR Signaling to Ameliorate Metabolic Dysfunction-associated Fatty Liver Disease.","authors":"Yuan Wang, Yan-Fang Chen, Yi-Xuan Cong, Yin-Peng Wang, Peng Liu, Ya-Ping Du, Juan Zhang, Xin-Cen Wang, Tong-Cheng Xu, Andrew J Sinclair, Duo Li, Xiao-Fei Guo","doi":"10.1016/j.jnutbio.2025.110136","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2025.110136","url":null,"abstract":"<p><p>Accumulating evidence has shown that n-3 polyunsaturated fatty acids (PUFA) intervention contributes to ameliorating metabolic dysfunction-associated fatty liver disease (MAFLD); however, the underlying mechanism through which n-3 PUFA alleviate MAFLD remains elusive. Critical gut microbiota-modified metabolites and host targets have been implicated in the initiation and development of MAFLD. Here, a case-control study was performed which indicated that gut microbiota-modified bile acids, notably serum hydeoxycholic acid (HDCA) species, were significantly lower in MAFLD subjects compared with the healthy controls and were negatively associated with n-3 PUFA proportions in red blood phospholipids, suggesting a link between n-3 PUFA, HDCA and MAFLD. The causality was further confirmed by a double-blind, randomized placebo-controlled trial which showed that n-3 PUFA supplementation significantly increased serum HDCA concentrations in MAFLD subjects in comparison with the control group. The MAFLD mouse model showed that administration of n-3 PUFA mediated hepatic peroxisome proliferator-activated receptor alpha signaling to upregulate oxysterol 7α-hydroxylase (CYP7B1)-centered alternative bile acids synthetic pathway, contributing to increased HDCA concentrations. Administering HDCA to high-fat diet (HFD)-fed mice demonstrated that HDCA acts as an intestinal farnesoid X receptor (FXR) antagonist that decreased intestinal and hepatic ceramide accumulation, thereby ameliorating the MAFLD phenotype. Administration of C16:0-ceramide to HDCA-treated mice reversed the metabolic benefits of HDCA to alleviate hepatic steatosis. Altogether, this work revealed that n-3 PUFA facilitated HDCA synthesis through alternative bile acids synthetic pathway, which mediates the FXR-ceramide axis, providing a novel insight to ameliorate MAFLD.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110136"},"PeriodicalIF":4.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228471","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}