Journal of Nutritional Biochemistry最新文献

{"title":"Resveratrol alleviates hippocampal oxidative stress, neuroinflammation and pyroptosis and reduces anxiety-like behavior in broilers under cold exposure.","authors":"Senyue Yang, Ziye Zang, Deyang Miao, Ziang Zhang, Xinqi Wang, Ying Zhang, Shijie Zhang, Haidong Wei, Jianhong Li","doi":"10.1016/j.jnutbio.2026.110523","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2026.110523","url":null,"abstract":"<p><p>Resveratrol (Res) exhibits antioxidant properties and neuroprotection. To investigate its protective effect, 576 one-day-old broilers were assigned to eight groups, reared under normal temperature or cold exposure (CE) and received the basal diet with 0, 250, 500, and 750 mg/kg Res, respectively. Broilers underwent behavioral tests, and hippocampus were collected. The results showed that after CE, the latency to first move and vocalise in open field test, induction times in tonic immobility test, and the latency to move, eat and vocalise in attention bias test were increased, while the numbers of movement steps and total vocalizations in attention bias test were decreased. Hematoxylin-eosin and Nissl staining displayed the perivascular aggregation of inflammatory cells and necrosis, disordered and sparse neurons, and reduced number of neurons in CE-broiler hippocampus. Transmission electron microscopy showed that CE caused synaptic terminals swelling and reduced the number of synaptic vesicles. Res restored abnormal changes in behaviors, histopathology and microstructure. CE decreased the CAT, T-SOD, GSH-px, and T-AOC activities, increased the H₂O₂ and MDA levels, upregulated the expression of genes and proteins related to inflammation (NF-κBp65, TNF-α, IL-2, IL-6, IL-8, IL-17) and pyroptosis (NLRP3, Caspase-1, GSDMD, ASC, IL-1β, IL-18), and depressed the expression of SIRT1 and BDNF/TrκB (CREB, FRS2, CRF, BRAF, PI3K) mRNA and proteins. Res normalized the abnormal expression in CE-broiler hippocampus. Overall, 500 mg/kg Res, an optimal supplementation dosage, relieved oxidative and inflammatory injuries by enhancing antioxidative capacity and inhibiting NF-κB signaling and NLRP3 inflammasome, alleviating anxiety-like behaviors in CE-broilers via modulating the SIRT1/BDNF/TrκB signaling.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110523"},"PeriodicalIF":5.2,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224422","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":"Paeoniflorin Promotes Mitophagy Against Acute Kidney Injury via PRDX5-Dependent Inhibition of RACK1.","authors":"Long-Hao Jia, Yi-Xu Song, Yu-Rou Li, Qiu-Xiang Bai, Jian Jia, Zi-Lan Yao, Rui-Zhi Tan, Li Wang","doi":"10.1016/j.jnutbio.2026.110520","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2026.110520","url":null,"abstract":"<p><p>Impaired mitophagy is a core driver of acute kidney injury (AKI), yet effective pharmacological strategies to restore this mitochondrial quality control mechanism remain limited. Paeoniflorin (Pae), a natural monoterpene glycoside, has shown renoprotective potential, but whether and how it regulates mitophagy remain unclear.. This study investigated the protective effects of Pae in mice subjected to bilateral renal ischaemia-reperfusion injury (IRI) and in cisplatin-treated TCMK-1 cells, with renal tubular-specific Prdx5 conditional knockout (Prdx5-CKO) mice used to determine the requirement for PRDX5. Pae treatment dose-dependently ameliorated renal tubular injury, reduced serum creatinine and BUN levels and inflammatory cytokine expression, and restored mitochondrial DNA copy number.Mechanistically, Pae upregulated PRDX5, which interacted with and negatively regulated RACK1. PRDX5 deficiency abolished the protective effects of Pae, aggravated renal injury, and further suppressed PINK1/Parkin expression. Conversely, RACK1 overexpression suppressed PINK1/Parkin and induced cellular injury, while RACK1 knockdown restored mitophagy and alleviated cisplatin-induced damage. Critically, the renoprotective effect of Pae was strictly PRDX5-dependent, as RACK1 knockdown rescued Pae efficacy in PRDX5-deficient cells. These findings demonstrate that Pae alleviates AKI by activating PINK1/Parkin-mediated mitophagy through the PRDX5/RACK1 signalling axis, identifying PRDX5 as an indispensable therapeutic target and revealing a novel mechanism for maintaining mitochondrial homeostasis in AKI.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110520"},"PeriodicalIF":5.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216472","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":"The Mechanism of S-adenosylhomocysteine Hydrolase in Regulating Podocyte Apoptosis and Diabetic Nephropathy via Moap1.","authors":"Xin Dai, Tianjiao Cui, Lokyu Cheng, Si Liu, Yongyi Wang, Mingjun Pan, Wenen Su, Ke Xu, Yumei Zhang, Shaohui Deng, Xiaohua Wang, Yunjun Xiao","doi":"10.1016/j.jnutbio.2026.110522","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2026.110522","url":null,"abstract":"<p><p>Elevated levels of S-adenosylhomocysteine (SAH) in patients with diabetes are closely associated with renal dysfunction. Inhibition of SAH hydrolase (SAHH) increases SAH levels, promotes apoptosis, and exacerbates streptozotocin (STZ)-induced diabetic nephropathy. However, the precise mechanism by which SAHH inhibition induces podocyte apoptosis remains unclear. This study aimed to investigate how SAHH inhibition specifically induces podocyte apoptosis and to elucidate the underlying molecular mechanisms. We established an STZ-induced podocyte-specific SAHH knockout mouse model and an in vitro model of high-glucose-treated podocytes. Our results showed that podocyte-specific SAHH deletion significantly exacerbated streptozotocin (STZ)-induced diabetic kidney injury. SAHH inhibition significantly upregulated the expression of modulator of apoptosis 1 (Moap1), which in turn promoted podocyte apoptosis through activation of the pro-apoptotic protein BAX. Knockdown of Moap1 partially reversed this apoptotic phenotype. Mechanistically, SAHH inhibition downregulated DNA methyltransferase 3b (DNMT3b) expression, leading to hypomethylation of the Moap1 promoter and subsequent upregulation of Moap1 transcription. ChIP-qPCR and dual-luciferase reporter assays confirmed that DNMT3b directly bound to the region of the Moap1 promoter and regulated its transcriptional activity. Restoration of DNMT3b expression reversed Moap1 upregulation and partially rescued the apoptotic phenotype induced by SAHH inhibition. Collectively, these findings demonstrate that SAHH inhibition promotes podocyte apoptosis by upregulating Moap1 expression through a DNMT3b-dependent hypomethylation mechanism, which in turn activates BAX. This study provides novel potential therapeutic targets for diabetic nephropathy with elevated SAH levels.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110522"},"PeriodicalIF":5.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216524","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":"Metabolic Reprogramming by Time-Restricted Feeding Confers Resistance to PM_2.5-Induced Metabolic Disturbances in Adipose Tissue.","authors":"Xiangyi Yuan, Chengyang Ge, Mingmeng Zheng, Yulu Zhou, Zhaoyi Zhou, Zhengyong Zhang, Li Qin, Lu Zhang, Tong Hou, Cuiqing Liu, Ran Li","doi":"10.1016/j.jnutbio.2026.110521","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2026.110521","url":null,"abstract":"<p><p>Recent research indicates that exposure to fine particulate matter (PM_2.5) not only impairs the respiratory system but also disturbs adipose tissue homeostasis, contributing to rising obesity rates and systemic metabolic disturbances. Time-restricted feeding (TRF), a dietary approach that confines daily food consumption to specific time windows, has demonstrated significant potential in preventing and managing metabolic disorders. However, it remains unclear if TRF can alleviate PM_2.5-induced adipose tissue dysfunction, and the mechanisms involved require investigation. We established a PM_2.5-exposed male mouse model and randomly assigned the animals to four groups: filtered air (FA), PM_2.5 exposure, TRF+FA, and TRF+PM_2.5. The PM_2.5 and TRF+PM_2.5 groups underwent whole-body PM_2.5 exposure in inhalation chambers, while the remaining groups were maintained under FA conditions. Mice in the TRF+FA and TRF+PM_2.5 groups were subjected to an 8-hour feeding window during the active phase (ZT16-ZT24). Our results indicated that PM_2.5 exposure induced systemic energy metabolism dysregulation and obesity, characterized by reduced heat production and metabolic rate, along with adipocyte hypertrophy, lipid droplet expansion, adipokine dysregulation, and inflammatory activation in both inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT). Furthermore, PM_2.5 significantly suppressed thermogenesis, impaired oxidative phosphorylation, disrupted mitochondrial quality control networks, and downregulated the AMPK/SIRT1/PGC-1α signaling pathway. Notably, TRF intervention reactivated these signaling pathways, systematically reversed the multi-level pathological alterations, and restored mitochondrial homeostasis and energy metabolic balance. This study suggests for the first time that TRF counteracts adipose tissue dysfunction caused by PM_2.5, offering a promising lifestyle intervention strategy against environment-related metabolic diseases.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110521"},"PeriodicalIF":5.2,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207057","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 Arginine Drives Spermidine Synthase-Mediated Endogenous Spermidine Biosynthesis to Promote Steroidogenesis and Ovarian Development in the Swimming Crab (Portunus trituberculatus).","authors":"Xiaoyue Li, Tiantian Xu, Zheng Tang, Yinqiu Tian, Xishuai Cui, Peng Sun, Wenli Zhao, Tingting Zhu, Min Jin, Qicun Zhou","doi":"10.1016/j.jnutbio.2026.110519","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2026.110519","url":null,"abstract":"<p><p>Ovarian development is governed by coordinated metabolic and endocrine signals. Although arginine (Arg) is vital for ovarian development, the mechanism underlying the coupling of amino‑acid metabolism with steroidogenesis by dietary Arg remains elusive in crustaceans. Here, integrated transcriptomic and metabolomic analyses were employed to elucidate the molecular mechanism underlying Arg-regulated ovarian development in the swimming crab (Portunus trituberculatus). Crabs fed a diet containing 2.65% Arg exhibited the highest gonadosomatic index and accelerated ovarian development. Hepatopancreatic metabolomics revealed enhanced polyamine metabolism and energy metabolism, while ovarian multi-omics identified spermidine synthase (SPDS) as a key regulator of spermidine biosynthesis and steroidogenesis. Functional validation using ovarian explants and Drosophila melanogaster S2 cells demonstrated that Arg activated polyamine metabolism and steroidogenic pathways. Moreover, spds knockdown markedly inhibited downstream steroidogenic gene expression in ovarian explants and S2 cells. Exogenous spermidine supplementation enhanced steroid synthesis in S2 cells, but the level remained significantly lower than that of the Arg group. Functional validation indicated that spds is a key target in Arg-mediated ovarian development, and the endogenous spermidine produced by spds regulates ovarian development in crustaceans. In conclusion, these findings demonstrate that dietary Arg promotes ovarian development by activating an SPDS-dependent endogenous spermidine biosynthetic pathway that couples polyamine metabolism with steroidogenesis, providing mechanistic insights into amino acid-regulated reproduction in crustaceans.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110519"},"PeriodicalIF":5.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165806","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":"Veratric acid ameliorates metabolic-dysfunction-associated fatty liver disease via targeting PPARG.","authors":"Siqi Liu, Tingli Pan, Qiuchen Cheng, Qichao Liao, Yutian Wei, Jianfeng Wu, Zhen Ma, Lin Yu, Shi Liu, Yuehui Liang, Xue Liang, Yixing Li, Lei Zhou, Yunxiao Liang","doi":"10.1016/j.jnutbio.2026.110518","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2026.110518","url":null,"abstract":"<p><p>Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most common metabolic syndromes worldwide. Its pathogenesis is multifactorial, involving disruptions in lipid metabolism, insulin resistance, chronic inflammation, and mitochondrial dysfunction. Veratric acid (VA), a naturally occurring phenolic compound, is known for its antioxidant and anti-inflammatory properties; however, its therapeutic potential and underlying mechanisms in the context of MAFLD remain largely uncharacterized. This study aimed to investigate the protective effects and underlying mechanisms of VA in a high-fat diet induced mouse model of MAFLD. In this study, C57BL/6J mice were fed an HFD with or without VA supplementation. Metabolic phenotypes, hepatic steatosis, and serum biochemical parameters were evaluated. In vitro experiments were conducted in HepG2 cells to assess lipid accumulation, mitochondrial function, oxidative stress, and gene expression. Network pharmacology, molecular docking, CETSA, and DARTS assays were employed to identify potential targets. The results demonstrated that VA significantly alleviated HFD-induced weight gain, adipose tissue accumulation, and hepatic steatosis. VA also improved glucose homeostasis, reduced serum lipid levels, and ameliorated liver injury. Mechanistically, VA modulated lipid metabolism by enhancing fatty acid β-oxidation and lipolysis. Network pharmacology, molecular docking, and biochemical validation further identified peroxisome proliferator-activated receptor gamma (PPARG) as a key target of VA. VA stabilized the PPARG protein, thereby promoting lipid metabolic reprogramming. These findings provide new insights into the bioactivity of VA and suggest its potential as a natural therapeutic agent for MAFLD.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110518"},"PeriodicalIF":5.2,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167181","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":"Ketogenic diet induces metabolic remodeling and alters myogenic markers in skeletal muscle of obese male mice subjected to medial meniscus destabilization.","authors":"Karolina Górecka, Thomas Solé, Kamila Soboska, Karim Chikh, Asmaa El Maarbani, Luciano Pirola, Maura Strigini, Aneta Balcerczyk","doi":"10.1016/j.jnutbio.2026.110515","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2026.110515","url":null,"abstract":"<p><p>Osteoarthritis (OA) is strongly associated with obesity, and weight reduction is recommended to reduce joint loading and improve symptoms. However, the effects of ketogenic diet (KD)-induced weight loss on skeletal muscle under combined metabolic and biomechanical stress remain poorly understood. We investigated skeletal muscle adaptation to KD in a mouse model that combined obesity with knee joint injury. Male C57BL/6J mice were rendered obese by high-fat diet feeding and subjected to destabilization of the medial meniscus. Following surgery, animals remained on high-fat diet (HFD) or were switched to chow diet (CD) or KD for 8 weeks. Gastrocnemius muscle was analysed at the molecular level, and serum underwent targeted metabolomic profiling. KD induced weight loss, reduced glycemia and increased circulating β-hydroxybutyrate without decreasing absolute gastrocnemius mass or causing sustained deterioration in motor performance. In skeletal muscle, KD increased Acat1 expression and induced a transcriptional profile consistent with enhanced capacity for lipid-derived substrate utilization, including increased Ppargc1a, Acadl, Cpt1b and Pdk4 expression. These changes were accompanied by selective remodelling of circulating acylcarnitines, particularly long-chain and hydroxyacylcarnitine species, indicating altered systemic. KD also increased expression of the myogenic-associated markers Pax7, Myf5 and MyoD1 hinting at a possible alteration in satellite cell state and pathways connected to myogenesis. Overall, KD promoted selective systemic and skeletal muscle metabolic remodelling in, characterized by altered lipid-derived substrate handling, activation of an oxidative transcriptional program and transcriptional modulation of myogenic-associated markers without sustained deterioration in motor performance during weight loss.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110515"},"PeriodicalIF":5.2,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of different gestational diabetes treatments on myo-inositol levels and placental insulin signalling.","authors":"Antonio Gázquez, Valentina Origüela, María Teresa Prieto-Sánchez, José Eliseo Blanco-Carnero, Elvira Larqué","doi":"10.1016/j.jnutbio.2026.110514","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2026.110514","url":null,"abstract":"<p><p>Myo-inositol (MI) is a precursor of inositol-3-phosphate, which participates in the insulin receptor pathway. Glucose enhances urinary MI excretion, which could affect gestational diabetes mellitus (GDM) management. The relationship between MI levels and GDM treatment remains unclear, raising questions about potential MI supplementation. The aim of this study was to evaluate MI levels in GDM women treated with either diet or insulin, and their associations with glycaemia and placental insulin signalling. MI was quantified in 23 women with GDM treated with diet (GDM-Diet), 20 GDM treated with insulin (GDM-Insulin) and 25 healthy non-GDM (control). Samples were collected at both the third trimester of pregnancy and at delivery in serum, urine, placenta and cord blood. Placental insulin cascade proteins were assessed by western blot. MI concentration in serum and placenta were decreased in GDM women at delivery, especially in the GDM-diet group. Furthermore, diabetic patients showed greater urinary excretion of MI already at third trimester. Nevertheless, cord MI was not affected by GDM. Placental p-Akt was strongly associated with placental MI (R=0.415, P=0.006), and its levels were lower in GDM-diet group (P=0.031). Insulin treatment tended to normalize maternal MI levels and insulin signalling, whereas GDM treated with diet had lower MI concentrations in both serum and placenta compared to controls. Women with GDM show reduced serum and placental MI concentrations than controls, linked to impaired insulin signalling. Women with GDM managed with diet show the greatest MI deficit and thus may therefore represent a target population for future supplementation trials.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110514"},"PeriodicalIF":5.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137078","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 Zeaxanthin Attenuates Cigarette Smoke-Induced COPD by Suppressing ERK-Driven Apoptosis.","authors":"Ziyi Liu, Qinshi Liang, Yifan Liu, Huiru Zheng, Huihui Zeng, Hongliang Zhang","doi":"10.1016/j.jnutbio.2026.110517","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2026.110517","url":null,"abstract":"<p><strong>Background: </strong>Dietary zeaxanthin's role in COPD remains underexplored.</p><p><strong>Methods: </strong>A multi-dimensional approach integrating NHANES epidemiological data, multi-omics analyses (network pharmacology, transcriptomics, molecular docking), and experimental validation in a CSE-induced mouse model and HBE cells.</p><p><strong>Results: </strong>NHANES analysis revealed an inverse association between zeaxanthin intake and COPD risk. Multi-omics identified MAPK1 (ERK2) as a core target, with molecular docking predicting favorable zeaxanthin-MAPK1/MAPK3 interactions. Zeaxanthin alleviated emphysema, improved lung function, and reduced apoptosis/inflammation in vivo, and protected HBE cells in vitro. Mechanistically, it dose-dependently inhibited ERK phosphorylation and downstream cleaved caspase-3 activation. PMA-mediated reactivation of ERK partially reversed the anti-apoptotic effect of zeaxanthin.</p><p><strong>Conclusion: </strong>Dietary zeaxanthin protects against COPD by suppressing the ERK-mediated apoptotic pathway, supporting its potential as a nutritional intervention.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110517"},"PeriodicalIF":5.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137110","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":"Gut microbiota-derived indole-3-propionic acid suppresses hepatic CYP2E1 expression in mice.","authors":"Yige Wang, Pan Huang, Xiang Li, Jun Yang, Nan Jing, Vladimir Yeliseyev, Zongwei Cai, Guodong Zhang","doi":"10.1016/j.jnutbio.2026.110516","DOIUrl":"https://doi.org/10.1016/j.jnutbio.2026.110516","url":null,"abstract":"<p><p>Hepatic cytochrome P450 2E1 (CYP2E1) is an important P450 enzyme involved in the metabolism of numerous xenobiotics. Notably, it contributes to the metabolic activation of many pro-carcinogenic and toxic compounds, thereby playing a critical role in human health and disease development. Previous studies suggest that gut microbiota modulate hepatic CYP2E1 expression; however, the microbiota's effects are inconsistent, and the underlying mechanisms remain unknown. Here, we show that the gut microbiota suppress hepatic CYP2E1 expression, at least in part, through the gut microbial metabolite indole-3-propionic acid (IPA). Hepatic CYP2E1 expression was significantly increased in germ-free and antibiotic-treated mice compared with conventionally raised mice, indicating that the gut microbiota reduce hepatic CYP2E1 expression. Furthermore, we found that IPA, a gut microbial metabolite, accumulates at high levels in the livers of conventionally raised mice but is barely detectable in germ-free or antibiotic-treated mice. Finally, IPA treatment reduced CYP2E1 expression both in liver cells and in mice. Collectively, these findings demonstrate that the gut microbiota suppress hepatic CYP2E1 expression, at least in part, through microbial metabolites, particularly IPA. These findings suggest a novel mechanism by which the gut microbiota regulate host metabolism and human health.</p>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":" ","pages":"110516"},"PeriodicalIF":5.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127398","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}