Journal of Nutritional Biochemistry最新文献

{"title":"Isosteviol attenuates myocardial ischemia-reperfusion damage by modulating Akt/GSK3β phosphorylation and mitochondrial permeability transition pore opening in female rats","authors":"Victoria Evangelina Mestre Cordero ,&nbsp;Romina Hermann ,&nbsp;María de las Mercedes Fernández Pazos ,&nbsp;Federico Joaquín Reznik ,&nbsp;Lucia Sánchez ,&nbsp;Julieta Mourglia ,&nbsp;Juliana Perego ,&nbsp;Débora Elisabet Vélez ,&nbsp;Juan Manuel Prieto ,&nbsp;María Gabriela Marina Prendes","doi":"10.1016/j.jnutbio.2025.110059","DOIUrl":"10.1016/j.jnutbio.2025.110059","url":null,"abstract":"<div><div>Presently, numerous studies are exploring the cardioprotective effects of compounds derived from native plants. In particular, research suggests that isosteviol may exert potential cardioprotective effects, linked to Protein Kinase B (Akt) activation. This study aimed to explore the role of Akt and GSK-3β in the cardioprotective effects mediated by the acute administration of isosteviol in Langendorff-perfused female rat hearts subjected to ischemia-reperfusion (Is-Rs). Hearts from female Wistar rats were subjected to Is-Rs. Isosteviol (5 µM) was added to the perfusate 10 min before ischemia. Wortmannin, a phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor (100 nM), was added 15 min before ischemia. Mitochondrial ultrastructure was analyzed by electron microscopy, and the phosphorylation profile of Akt and GSK-3β were studied by western blot. Effects on mitochondrial permeability transition pore (MPTP) opening was assessed via calcium retention capacity (CRC). Docking studies using AutoDock4-Bias were performed to explore potential interactions between isosteviol and Akt or GSK-3β. ANOVA, <em>n</em>=6/group. Isosteviol improved cardiac post-ischemic mechanical recovery and reduced infarct size. It also increased the phosphorylation of Akt and GSK-3β after Is-Rs. Isosteviol treatment prevented MPTP opening, evidenced by the increase in CRC, and preserved mitochondria structure from the expected deterioration toward the end of Is-Rs protocol. All these beneficial effects were prevented, at least in part, by wortmannin. Finally, the results showed that isosteviol interacted with favorable binding energies at the phosphoinositide-binding site of Akt and the kinase site of GSK-3β. These results suggest that cardioprotective effects of isosteviol could be partly mediated by Akt activation, GSK-3β phosphorylation and the inhibition of MPTP opening.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110059"},"PeriodicalIF":4.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812153","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":"Oleic acid-enriched diet improves maternal lactation performance and neonatal growth through GPR40 and GPR120 signaling pathways","authors":"Min Tian ,&nbsp;Zhenting He ,&nbsp;Siyu Yuan ,&nbsp;Tongbin Lin ,&nbsp;Senlin Su ,&nbsp;Dongpang Chen ,&nbsp;Xiangfang Zeng ,&nbsp;Wutai Guan ,&nbsp;Shihai Zhang","doi":"10.1016/j.jnutbio.2025.110062","DOIUrl":"10.1016/j.jnutbio.2025.110062","url":null,"abstract":"<div><div>Oleic acid represents a major monounsaturated component of milk fat, yet its specific roles in lactation remain unclear. This study evaluated the impact of an oleic acid-enriched diet on sow lactation performance, milk composition, and offspring growth, and investigated the underlying regulatory mechanisms. Eighty sows were randomized to either a standard diet or a high-oleic acid diet formulation throughout gestation and lactation. The milk fat content, fatty acid profiles, and weaning body weight of the litter were measured. In parallel, porcine mammary epithelial cells (pMECs) were treated with oleic acid, with or without selective inhibitors of GPR40 and GPR120, to dissect receptor-mediated effects on triglyceride synthesis and fatty acid transporter expression. Dietary enrichment with oleic acid significantly increased milk fat content, shifted the milk fatty acid profile toward higher monounsaturated levels, and resulted in greater weaning body weight in piglets. Enhanced transfer of immunoglobulins, antioxidant enzymes, and inflammatory mediators from sow to neonate further suggested improved neonatal resilience. In pMECs, oleic acid upregulated CD36, FATP4, and FABP3 expression and boosted triglyceride synthesis via activation of both GPR40 and GPR120. Pharmacological blockade revealed that GPR40 inhibition reduced triglyceride accumulation by approximately 37.6%, whereas GPR120 blockade produced a more modest decrease. Together, these findings demonstrate that oleic acid enhances milk fat production and supports offspring growth through GPCR-dependent signaling, with GPR40 playing the dominant role.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110062"},"PeriodicalIF":4.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804335","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":"Oral supplementation with sesaminol, a sesame-related lignan, ameliorates ethanol-induced dysbiosis of the gut microbiota and increases the gut luminal short-chain fatty acid concentrations of mice","authors":"Daiki Oikawa ,&nbsp;Hideo Ohira ,&nbsp;Yuichi Aoki ,&nbsp;Yoichi Kurokawa ,&nbsp;Ayano Omura ,&nbsp;Kunio Kiyomoto ,&nbsp;Yoshio Fujioka ,&nbsp;Toru Nakayama","doi":"10.1016/j.jnutbio.2025.110052","DOIUrl":"10.1016/j.jnutbio.2025.110052","url":null,"abstract":"<div><div>Chronic ethanol consumption significantly increases the risk of colorectal cancer. The pathogenesis of ethanol-related colorectal cancer involves oxidative stress and inflammation induced by ethanol in the colon and rectum, as well as dysfunction of the gut barrier and greater intestinal permeability. Previously, we demonstrated that chronic oral ethanol administration in mice leads to dysbiosis of the fecal microbiota, similar to that which characterizes human inflammatory bowel disease. In addition, this ethanol-induced gut pathophysiology was alleviated by the oral administration of sesaminol, a lignan derived from sesame that is known for its potent antioxidant activity. In the present study, we investigated the effects of oral sesaminol administration on the fecal microbiota and short-chain fatty acid (SCFA) profiles of mice that were chronically orally administered ethanol or not. Chronic ethanol administration reduced the abundances of fecal bacterial taxa that produce butyric acid, thereby reducing the fecal butyric acid content. The oral administration of sesaminol (2.5 mg/d) mitigated the ethanol-induced dysbiosis of the gut microbiota and increased the luminal SCFA content, and particularly that of butyric acid. The effects of oral sesaminol administration on ethanol-induced gut pathophysiology may be mediated, at least in part, by the anti-inflammatory and gut barrier–protective properties of butyric acid.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110052"},"PeriodicalIF":4.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799386","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":"Preventive effect of eicosapentaenoic acid on the exacerbation of concanavalin A–induced liver injury aggravated by a short-term high-fat diet","authors":"Eri Nanizawa ,&nbsp;Yuki Katoh ,&nbsp;Yuki Tamaki ,&nbsp;Shun Otsuka ,&nbsp;Naoyuki Hatayama ,&nbsp;Tetsuya Ishikawa ,&nbsp;Shuichi Hirai ,&nbsp;Munekazu Naito","doi":"10.1016/j.jnutbio.2025.110049","DOIUrl":"10.1016/j.jnutbio.2025.110049","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatohepatitis is an advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD) and is associated with progression to cirrhosis and liver cancer. Although early intervention is crucial, studies focusing on the early stages of MASLD are limited. Patients with MASLD are expected to have an imbalance of n-3 and n-6 polyunsaturated fatty acids (PUFAs). In a previously developed short-term high-fat diet (HFD) model (C57BL/6, male), we demonstrated that only 4 d of HFD intake exacerbated concanavalin A (Con A)–induced liver injury (10 mg/kg), suggesting increased liver vulnerability even in the absence of clinical symptoms. Herein, alterations in n-3 and n-6 PUFA levels and related inflammatory mechanisms during early HFD exposure were investigated to explore early prevention strategies for MASLD. Liver and serum samples were collected from HFD-fed mice for 4 d and analyzed for n-3 and n-6 PUFA levels using gas chromatography–mass spectrometry. The results revealed that levels of eicosapentaenoic acid (EPA), an n-3 PUFA known for its anti-inflammatory effects, decreased in the liver and serum, whereas the levels of arachidonic acid, an n-6 PUFA that promotes inflammation, increased. Further analysis showed that supplementing EPA (100 mg/kg), which was reduced during short-term HFD intake, significantly mitigated the worsening of Con A-induced liver injury, primarily owing to its anti-inflammatory and anticoagulant effects. These findings in mice suggest that early EPA supplementation may effectively prevent liver injury and reduce the risk of MASLD progression, even before the emergence of clinical symptoms.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110049"},"PeriodicalIF":4.9,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794766","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":"Fisetin ameliorates neurobehavioral deficits in bile duct ligated rat model by restoring spine density and memory gene expression","authors":"Shiwangi Gupta ,&nbsp;Vikas Rishi ,&nbsp;Aanchal Aggarwal","doi":"10.1016/j.jnutbio.2025.110050","DOIUrl":"10.1016/j.jnutbio.2025.110050","url":null,"abstract":"<div><div>Chronic liver damage is characterized by cognitive impairments primarily due to metabolic imbalance notably hyperammonemia, termed as hepatic encephalopathy (HE). The present study investigated the neuroprotective potential of fisetin, a bioactive flavonoid, in bile duct-ligated (BDL) rat model that mimics HE. BDL rats exhibited significant liver morphological alterations, driven by inflammation and fibrosis causing metabolic imbalance and persistent chronic liver damage. These rats further demonstrated deficits in spatial memory, learning, and object recognition, as observed through various behavioral paradigms including morris water maze, barnes maze, Y-maze, and novel object recognition test. These cognitive deficits were accompanied by neurodegeneration, reduced spine density, disrupted expression of synaptic markers, and altered brain metabolite levels. Fisetin supplementation (25 mg/kg, p.o. for 28 d post-BDL surgery) to BDL rats significantly improved cognitive performance in the behavioural tests. Additionally, fisetin restored spine density and clustering patterns, upregulated key memory-associated genes (PSD95, synaptophysin, synaptotagmin-1), and reduced brain levels of ammonia, glutamate, and glutamine, which correlated with enhanced neurobehavioral outcomes. Histological assessments showed significantly reduced neuronal degeneration in BDL rats supplemented with fisetin, suggesting its ability to ameliorate HE-associated neurodegeneration. These findings collectively underscore fisetin’s neuroprotective potential in BDL rats by mitigating neurodegeneration, preserving synaptic integrity, and enhancing cognitive function.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110050"},"PeriodicalIF":4.9,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794765","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 presence of a H. pylori infection blunted the upregulation of iron-related duodenal proteins in response to anemia","authors":"Jagadish Ramasamy ,&nbsp;Monica Peter ,&nbsp;Nikhitha Mariya John ,&nbsp;Jithu James Varghese ,&nbsp;Shiny Prem ,&nbsp;Joe Varghese ,&nbsp;Thenmozhi Mani ,&nbsp;Ebby George Simon ,&nbsp;Molly Jacob","doi":"10.1016/j.jnutbio.2025.110048","DOIUrl":"10.1016/j.jnutbio.2025.110048","url":null,"abstract":"<div><div><em>Helicobacter pylori</em> (<em>H. pylori</em>) infection is often associated with iron-deficiency anemia. The mechanisms that underlie this association are unclear. We attempted to determine whether the presence of a <em>H. pylori</em> infection affected iron homeostasis. Patients with dyspepsia, who underwent an upper gastrointestinal endoscopy, were categorized into those without and with a <em>H. pylori</em> infection. Hematological and iron-related parameters and C-reactive protein (CRP) were estimated in their blood samples. Gene expression of proteins involved in iron absorption (divalent metal transporter 1 [DMT1], duodenal cytochrome B reductase [DCYTB], ferritin [FTN] and ferroportin [FPN]) was determined in duodenal mucosal samples. Hematological and iron-related parameters and CRP levels in blood, and gene expression of duodenal iron-related proteins were not significantly different in those without and with a <em>H. pylori</em> infection. When stratified into quartiles based on hemoglobin values, patients in the lower quartiles (in both groups) showed evidence of a lower iron status. Upregulation of duodenal DMT1 and FPN gene expression in response to anemia (a known physiological phenomenon) was seen in uninfected patients, but not in those with the infection. DYCTB expression was significantly lower in those with the infection, who expressed <em>H. pylori</em>-associated virulence factors, CagA and VacA. <em>H. pylori</em> infection did not significantly affect hematological parameters, blood markers of iron status and gene expression of duodenal proteins involved in iron absorption. However, the physiological response to upregulate DMT1 and FPN gene expression in response to anemia was attenuated in those with the infection.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110048"},"PeriodicalIF":4.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768708","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":"Policosanol ameliorates Post-Myocardial Infarction-induced neuronal damage and cognitive impairment in rats via suppressing miRNA-1","authors":"Asmaa M. Abdelghafour ,&nbsp;Mohamed Mahrous ,&nbsp;Mahmoud E. Zaher","doi":"10.1016/j.jnutbio.2025.110047","DOIUrl":"10.1016/j.jnutbio.2025.110047","url":null,"abstract":"<div><div>Heart-brain interaction is widely highlighted as a contributor to several cardiovascular and neurodegenerative diseases. Great interest has been focused on miRNAs as one of the possible molecular mechanisms of heart-brain interaction. Therefore, we aimed to investigate the potential neuroprotective effects of policosanol (POL), a commonly used hypocholesterolemic agent, versus cognitive impairment and neuronal damage in a post-myocardial infarction (MI) rat model. Additionally, we aimed to explore the molecular mechanisms through which POL may ameliorate this damage through its effects on miRNA-1 and its target genes. Post-MI-induced neuronal damage was induced in rats by isoproterenol (ISO) (100 mg/kg) given as two subcutaneous injections separated by 24-h interval. Then, rats were treated with POL (50 mg/kg/day, orally) for 4 weeks. Post-MI-induced cognitive dysfunction was characterized by the increased locomotor activity and the decreased spatial cognition ability in Y-maze test. Hippocampal <em>miRNA-1</em> expression was increased following MI and thereby, the hippocampal <em>BDNF</em> mRNA expression along with its contents of TrkB and CREB were decreased. Additionally, the hippocampal <em>FZD7</em> mRNA expression along with active β-catenin and NeuroD1 contents were decreased. Moreover, the cortical mRNA expression of <em>HSP70</em> and its contents of TPPP/P25 and BCL-2 were decreased, but cortical contents of BAX and caspase-3 were increased. Treatment with POL ameliorated these changes resulting in the alleviation of the post-MI-mediated neuronal damage and cognitive dysfunction. Our findings suggest a novel insight into one of the possible molecular mechanisms of POL neuroprotective effects versus Post-MI-induced neuronal damage and cognitive impairment at the miRNA level.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110047"},"PeriodicalIF":4.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765008","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 and mechanisms of nuciferine on constipation through regulation of the SCF/c-Kit/NF-κB/TLR4 signaling pathway in STC model mice","authors":"Lalai Zikela ,&nbsp;Xinyao Li ,&nbsp;Hui Zhou ,&nbsp;Hao Xu ,&nbsp;Huilin Zhu ,&nbsp;Zhuoli Yu ,&nbsp;Dingli Wang ,&nbsp;Jingru Gao ,&nbsp;Zhengran Ma ,&nbsp;Yiwen Gao ,&nbsp;Qiang Han","doi":"10.1016/j.jnutbio.2025.110045","DOIUrl":"10.1016/j.jnutbio.2025.110045","url":null,"abstract":"<div><div>This study aimed to investigate the therapeutic effects of nuciferine (Nuci) on a mouse model of slow transit constipation (STC) and to elucidate its underlying mechanisms, with a particular focus on its impact on the intestinal immune system and gut microbiota. STC was induced in mice using loperamide, and the animals were divided into normal control (NC), loperamide model (LOP), mosapride positive control (MOS), low-dose nuciferine (Nuci-L), and high-dose nuciferine (Nuci-H) groups. Comprehensive assessments were conducted through fecal analysis, intestinal transit tests, blood tests, histological examination (H&amp;E staining), Western Blot, RT-PCR, and 16S rRNA sequencing to evaluate the therapeutic effects of nuciferine and its mechanisms in STC mice. STC mouse model was successfully established, as evidenced by decreased fecal weight and water content, and prolonged defecation time. Nuci intervention significantly increased (<em>P&lt;.05</em>) fecal weight and water content, shortened defecation time, and reduced plasma motilin (MTL) levels in STC mice. Histological examination showed improvements in the distal colon of STC mice treated with Nuci. Western Blot and RT-PCR results indicated that Nuci upregulated SCF and c-Kit expression and downregulated TLR4 and NF-κB expression in the distal colon of STC mice. Gut microbiota sequencing revealed that Nuci improved gut microbiota abundance in STC mice, with changes in the abundance of specific bacterial phylum and genus. Nuciferine exhibits significant therapeutic effects on an STC mouse model by modulating the intestinal immune system and gut microbiota. These findings provide a new potential therapeutic option for STC and reveal the underlying mechanisms of nuciferine in regulating intestinal health and alleviating constipation.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110045"},"PeriodicalIF":4.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760373","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":"Sculpting liver-related injury in type 2 diabetes mellitus: Decoding serum ferritin's correlation and ferroptosis pathways","authors":"Bin Huang ,&nbsp;Wenjie Wen ,&nbsp;Xiangyu Ding ,&nbsp;Shandong Ye","doi":"10.1016/j.jnutbio.2025.110044","DOIUrl":"10.1016/j.jnutbio.2025.110044","url":null,"abstract":"<div><div>We aimed to assess whether serum ferritin levels are a risk factor for hepatic-related injury in patients with type 2 diabetes mellitus (T2DM) and investigate the role of ferroptosis in this pathological process. A retrospective cohort study and Mendelian randomization analysis were conducted to investigate the association between serum ferritin levels and liver-related outcomes. Furthermore, dB/dB mice and the GSE230674 dataset were used to analyze liver iron metabolism-related indicators and the ferroptosis pathway. Findings from this retrospective cohort study revealed that an elevated serum ferritin level is a relatively independent risk factor for liver-related injuries in patients with T2DM, including nonalcoholic fatty liver disease, hepatocellular injury, and cholestasis. Subgroup analysis suggested that this relationship was absent in patients with anemia. Mendelian randomization analysis indicated a causal relationship between increased hepatic iron storage and disruptions in iron metabolism, leading to elevated alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and direct bilirubin levels. Furthermore, diabetic mice with concomitant nonalcoholic fatty liver disease exhibited hepatic iron overload and activation of ferroptosis pathways. After intervention with ferrostatin-1, there was a reduction in liver injury-related biomarkers and suppression of ferroptosis. Serum ferritin is a risk factor for liver-related injuries in patients with T2DM with normal hemoglobin levels. In this context, activation of the ferroptosis pathway due to hepatic iron overload may play a crucial role. In addition, treatment strategies focused on inhibiting the hepatic ferroptosis pathway are promising.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110044"},"PeriodicalIF":4.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731861","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":"Hydroxytyrosol improved insulin resistance in male offspring born to high-fat diet dams by remodeling gut microbiota","authors":"Dongxin Yi ,&nbsp;Tao Li ,&nbsp;Yuji Xiao ,&nbsp;Xiao Li ,&nbsp;Bing Shao ,&nbsp;Ziyi Wu ,&nbsp;Qiangqiang Hao ,&nbsp;Feng Zhang ,&nbsp;Xue Zhang ,&nbsp;Guang Yang ,&nbsp;Cong Zhang ,&nbsp;Haoyuan Deng ,&nbsp;Xiance Sun ,&nbsp;Ningning Wang","doi":"10.1016/j.jnutbio.2025.110041","DOIUrl":"10.1016/j.jnutbio.2025.110041","url":null,"abstract":"<div><div>Maternal obesity during pregnancy and lactation critically influences offspring metabolic programming, increasing insulin resistance (IR) risk through gut microbiome alterations. This study investigated whether hydroxytyrosol (HT), a polyphenol, could exert metabolic benefits through intergenerational regulation of gut microbiota. Through dietary intervention and fecal microbiota transplantation experiments in pregnant and lactating C57BL/6 J dams, combined with 16S rRNA sequencing and interaction analysis, we found that maternal high-fat diet (60% fat for energy) during gestation and lactation caused obesity and IR-associated phenotypes in male offspring at 4 weeks of age, but not in female young pups. Oral gavage of HT (50 mg/kg) during pregnancy and lactation alleviated abnormal adipocyte hypertrophy, hyperplasia, and excessive leptin secretion in male offspring born to obese dams. Additionally, HT reduced systemic insulin intolerance, hyperglycemia, and hyperinsulinemia, decreased liver index and liver injury, attenuated hepatocyte ballooning, hepatic oxidative stress, and systemic inflammation, and restored hepatic PI3K/AKT signaling in male offspring. Furthermore, HT recovered intestinal barrier function and gut microbiota homeostasis in male offspring, especially the community structure represented by β-diversity, microbial dysbiosis index, and short-chain fatty acids content. Importantly, the beneficial effects of maternal HT ingestion on offspring IR were closely associated with gut microbiota remodeling and could be transmitted through intergenerational microbial inheritance between mothers and offspring. Together, our study indicated that the intergenerational transmission of microbiota may underlie maternal obesity-induced IR and that HT intake could be a promising intervention.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"146 ","pages":"Article 110041"},"PeriodicalIF":4.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731860","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}