Journal of Nutritional Biochemistry最新文献

{"title":"Food-derived chlorogenic acid prevents aortic aneurysm and dissection by nutritional restore branched-chain amino acid dyshomeostasis","authors":"Zhen-xiao Ma ,&nbsp;Ze-qun Yin ,&nbsp;Zi-an Feng ,&nbsp;Xiang-peng Xie ,&nbsp;Ao Li ,&nbsp;Shi-hao Fu ,&nbsp;Qi Yue ,&nbsp;Sheng Wang ,&nbsp;Li-kun Ma ,&nbsp;Ya-jun Duan ,&nbsp;Dan-qing He ,&nbsp;Jun-fang Wu ,&nbsp;Shuang Zhang ,&nbsp;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":"2026-04-01","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}

{"title":"Pre-but not post-natal nutritional restriction promotes mammary development","authors":"Xusheng Dong,&nbsp;Qiuling Hou,&nbsp;Yingyu Mu,&nbsp;Xueyan Lin,&nbsp;Zhiyong Hu,&nbsp;Yun Wang,&nbsp;Yizhao Shen,&nbsp;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":"2026-04-01","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}

{"title":"Metabolomics identifies riboflavin as a therapeutic agent for acute pancreatitis","authors":"Yuxin Shi ,&nbsp;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":"2026-04-01","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}

{"title":"The role of folic acid and vitamin B12 in gestational diabetes mellitus and offspring development: A narrative review","authors":"Jiayue Su ,&nbsp;Chenran Cai ,&nbsp;Ying Zhang ,&nbsp;Donglan Wang ,&nbsp;Sijia Yan ,&nbsp;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":"2026-04-01","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}

{"title":"Sulforaphane ameliorates DSS-induced colitis and secondary liver injury in mice: Proposed mechanism in the SCFAs-FFAR2/3-macrophage polarization axis","authors":"Jingyi Ren ,&nbsp;Xiaoxin Jiang ,&nbsp;Gejun Yu ,&nbsp;Wentao Wu ,&nbsp;Mengyuan Chen ,&nbsp;Yun Zhao ,&nbsp;Mengjie Yang ,&nbsp;Zuquan Zou ,&nbsp;Canxia He","doi":"10.1016/j.jnutbio.2025.110239","DOIUrl":"10.1016/j.jnutbio.2025.110239","url":null,"abstract":"<div><div>Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has shown therapeutic potential in inflammatory diseases. Our previous studies demonstrated that SFN ameliorates ulcerative colitis (UC) and restores gut microbiota composition in dextran sulfate sodium (DSS)-induced mice. In the present study, we further investigate the protective effects and underlying mechanisms of SFN against secondary liver injury associated with UC. The results revealed that SFN significantly alleviated pathological damage in both the colon and liver, improved liver function parameters, upregulated intestinal tight junction proteins and Muc2 expression, and inhibited inflammation in DSS-induced colitis mice. Additionally, SFN significantly elevated short-chain fatty acid (SCFA) concentrations, enhanced the expression of SCFA receptors (free fatty acid receptors 2 and 3, FFAR2/3), and modulated macrophage polarization by inhibiting M1 and promoting M2 phenotypes in the colon and liver. Collectively, these findings suggest that SFN may alleviate colitis and secondary liver injury by enhancing intestinal barrier function and reducing inflammatory responses, potentially via the SCFAs-FFAR2/3-macrophage polarization signaling cascade. Thus, SFN may serve as a promising adjunctive therapeutic agent for the prevention and treatment of UC.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110239"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781376","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":"Promoter demethylation and protein O-GlcNAcylation-mediated enhancement of fatty acid synthase contributes to hepatic steatosis and inflammation in MASLD","authors":"Zou-Han Lin ,&nbsp;Pin-I Chou ,&nbsp;Jia-Wei Chang ,&nbsp;Zong-Chen Lin ,&nbsp;Yuan-Ting Sun ,&nbsp;Ming-Hui Chang ,&nbsp;Shih-En Huang ,&nbsp;Yu-Min Yeh ,&nbsp;Chien-Chin Chen ,&nbsp;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":"2026-04-01","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}

{"title":"Complementary mechanisms of high-carbohydrate diets and ketogenic diets restore adult hippocampal neurogenesis and cognitive function in high-fat diet induced obesity in mice","authors":"Huiyoung Kwon ,&nbsp;Dong Soo Seo ,&nbsp;Yusra Ahmad ,&nbsp;Sungjun Park ,&nbsp;Jeongwoo Yoo ,&nbsp;Junhyeok Lee ,&nbsp;Ho Jung Bae ,&nbsp;Younghoon Jang","doi":"10.1016/j.jnutbio.2025.110245","DOIUrl":"10.1016/j.jnutbio.2025.110245","url":null,"abstract":"<div><div>High-fat diet (HFD)-induced obesity impairs cognition and hippocampal neurogenesis, linked to reduced metabolic flexibility between mitochondrial fatty acid <em>β</em>-oxidation (FAO) and cytosolic <em>de novo</em> lipogenesis (DNL). It is not fully understood if switching to a high-carbohydrate diet (HCD) or a ketogenic diet (KD) could reverse these HFD-induced deficits, or if they do so through different mechanisms. Male C57BL/6J mice received HFD for 8 weeks to induce obesity. Mice were then either maintained on the HFD or switched to an HCD or KD for an additional 8 weeks. We evaluated systemic metabolism (body weight, serum biochemistry), tissue-specific metabolic remodeling (RNA-seq, histology, RT-qPCR, Western blot) and cognitive function (Y-maze test, novel object recognition test). Both HCD and KD interventions reversed HFD‑induced systemic abnormalities, including reducing ALT/AST, cholesterol, and LDL, and attenuating hepatic steatosis and adipocyte hypertrophy. Metabolically, KD markedly increased β‑hydroxybutyrate, whereas HCD showed a distinct triglyceride profile. Both diets improved hippocampus-dependent working and recognition memory. Hippocampal RNA‑seq revealed diet-specific mechanisms. HCD enriched anabolic processes, including upregulation of glucose transporters (<em>Glut</em> 1, 2, 3, 4) and DNL pathway (ACLY-ACC-FASN-SCD1). Conversely, KD enriched AMPK signaling, increasing monocarboxylate transporters (<em>Mct</em> 1, 2, 4) for ketone uptake and activating the neurotrophic AMPK–ERK–CREB–BDNF pathway. In conclusion, post-HFD switching to HCD or KD restores hippocampal structure and cognition via complementary mechanisms. HCD drives a substrate-centric, lipogenic program supporting proliferation, whereas KD engages a signaling-centric, neurotrophic program enhancing plasticity. Metabolic flexibility is a promising target for obesity-associated cognitive decline.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110245"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878532","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":"Fatty acid composition of isoenergetic meals drives distinct postprandial immunometabolic responses in healthy adults: A randomized crossover pilot study","authors":"Elvira Marquez-Paradas ,&nbsp;Maria Torrecillas-Lopez ,&nbsp;Alfredo Corell-Almuraza ,&nbsp;Teresa Gonzalez-de la Rosa ,&nbsp;Luna Barrera-Chamorro ,&nbsp;Beatriz Bermudez ,&nbsp;Carmen M Claro-Cala ,&nbsp;Sergio Montserrat-de la Paz","doi":"10.1016/j.jnutbio.2025.110242","DOIUrl":"10.1016/j.jnutbio.2025.110242","url":null,"abstract":"<div><div>The postprandial period represents a critical and dynamic phase during which dietary components can acutely influence metabolic and immune functions. While the chronic effects of dietary fat quality are well characterized, their immediate postprandial immunometabolic impact remains poorly understood. To investigate the acute effects of energy-matched test meals enriched in saturated (SFA), monounsaturated (MUFA), or omega-3 long-chain polyunsaturated fatty acids (ω3-LCPUFA), compared to a fat-free control, on systemic metabolic and immune parameters in healthy adults. In this randomized, crossover pilot study, ten healthy participants consumed four test meals separated by 2-week washouts. Blood samples were collected at fasting, 2–3 h (peak), and 5–6 h (late phase) postprandially. Biochemical and immunological biomarkers were assessed. Statistical analyses included two-way repeated-measures ANOVA, linear mixed models, and area under the curve (AUC/iAUC) calculations. MUFA- and ω3-LCPUFA-enriched meals induced significantly greater postprandial changes in glucose, triacylglycerides, LDL-C, and C-peptide compared to the SFA and fat-free meals, particularly at the late postprandial phase. These effects were confirmed by AUC and iAUC analyses. In contrast, although transient changes in immune cell counts and humoral markers were observed over time, no significant differences between fat types were detected in postprandial immune responses. In healthy adults, the fatty acid composition of energy-matched meals acutely modulates key metabolic pathways in a fat-type-specific manner, whereas systemic immune parameters remain largely unchanged. These preliminary findings suggest a functional dissociation between postprandial metabolic and immune response and underscore the need to more sensitive or compartment-specific immune readouts in future nutritional research.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110242"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843726","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 methylglyoxal induces renal lipotoxicity primarily through adipose tissue dysfunction in mice fed normal or obesogenic high-fat diets","authors":"Medhavi Paramita Kondanna ,&nbsp;Yu-Ho Chang ,&nbsp;Hsin-Yi Yang ,&nbsp;Chi-Hao Wu ,&nbsp;Wan-Ju Yeh","doi":"10.1016/j.jnutbio.2025.110244","DOIUrl":"10.1016/j.jnutbio.2025.110244","url":null,"abstract":"<div><div>Unhealthy dietary patterns may impair renal function through elevated intake of methylglyoxal (MG) and advanced glycation end products (AGEs). While adipose tissue stores triglycerides (TG), its dysfunction promotes ectopic lipotoxicity, a process exacerbated by MG or AGEs. This study investigated if long-term dietary MG causes renal damage, mediated by adipose tissue dysfunction and ectopic lipid deposition. Eight-week-old male ICR mice were randomized into four groups for 52 weeks: normal diet and obesogenic high-fat diet (HFD), each with or without 1% MG in drinking water. Results showed that HFD significantly increased MG-AGEs in both adipose tissue and kidneys. Although HFD caused adipocyte hypertrophy <strong>and</strong> renal injury, no significant renal lipid accumulation was observed. In contrast, MG administration alone induced renal lipotoxicity and injury, manifested by increased TG concentrations in both the cortex and medulla. In HFD-fed mice, MG further exacerbated adipose tissue dysfunction by inhibiting angiogenesis and increasing interstitial collagen accumulation. Notably, the MG co-administration reduced adipocyte size, counteracting the hypertrophy caused by HFD alone. Furthermore, in the kidneys of these HFD-fed mice, MG led to increased medullary TG concentration and elevated collagen expression. In conclusion, HFD alone caused nonlipotoxic kidney injury without significant adipose dysfunction. However, MG administration consistently induced adipose tissue dysfunction and progressive renal lipotoxicity regardless of the diet. These findings suggest that MG-induced renal damage is primarily mediated by the dysfunction of adipose tissue, establishing a critical link between dietary MG intake and kidney disease progression, independent of obesogenic diet status.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110244"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843736","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":"Electroconvulsive therapy modulates brain plasticity in male depression: Links to gut microbial metabolites and diet-derived regulation of Wnt/BDNF signaling","authors":"Jiaming Ji ,&nbsp;Jinyan Guo ,&nbsp;Yin Huang ,&nbsp;Ke Chen ,&nbsp;Yuheng Xu ,&nbsp;Weijian Liang ,&nbsp;Zhenjia Lin ,&nbsp;Chang Xiong ,&nbsp;Xue Han ,&nbsp;Jun Liu ,&nbsp;Ziqing Hei ,&nbsp;Sufang Chen ,&nbsp;Weifeng Yao ,&nbsp;Chaojin Chen","doi":"10.1016/j.jnutbio.2025.110240","DOIUrl":"10.1016/j.jnutbio.2025.110240","url":null,"abstract":"<div><div>Electroconvulsive therapy (ECT) stands as the most effective intervention for treatment-resistant depression; however, its interaction with dietary regulation of the gut-brain axis has not been thoroughly explored. This study aimed to elucidate the mechanistic link between ECT, gut microbiota remodeling, short-chain fatty acid (SCFA) production, and neural plasticity. In this study, mice were subjected to chronic restraint stress (6 h/d for 28 consecutive days) to establish a depression-like model. Utilizing a translational approach that incorporated behavioral assessments, multimodal neuroimaging techniques such as PET-CT and laser speckle contrast imaging, along with multiomics analyses including metagenomics, metabolomics, and transcriptomics in rodent models, we demonstrated that ECT induced significant gut microbiota remodeling, characterized by an enrichment of SCFA-producing genera like <em>Lactobacillus</em> and <em>Bifidobacterium</em>. This remodeling was associated with restored intestinal barrier integrity and elevated plasma SCFA levels. Mechanistically, these microbial metabolites activated hippocampal Wnt/<em>β</em>-catenin signaling pathways, enhancing synaptic plasticity restoration, while concurrent probiotic supplementation further amplified brain-derived neurotrophic factor (BDNF) expression via SCFA-dependent epigenetic mechanisms. Neuroimaging corroborated the normalization of cerebral glucose metabolism and hemodynamic function post-ECT. In conclusion, our findings unveil a novel gut-brain communication pathway by which ECT exerts its antidepressant effects, positioning SCFAs as vital mediators connecting microbial metabolic alterations to neural plasticity. This research not only redefines the role of nutritional biochemistry in neuromodulation but also suggests the potential of microbial metabolite monitoring to tailor antidepressant therapies for enhanced efficacy.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"150 ","pages":"Article 110240"},"PeriodicalIF":4.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810429","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}