Journal of Nutritional Biochemistry最新文献

{"title":"Association between dairy-derived bioactive peptides and the risk of type 2 diabetes mellitus and cardiovascular diseases: Tehran lipid and glucose study","authors":"Fatemeh Ghasemi ,&nbsp;Farshad Teymoori ,&nbsp;Sajjad Roosta ,&nbsp;Mitra Kazemi Jahromi ,&nbsp;Hossein Farhadnejad ,&nbsp;Parvin Mirmiran ,&nbsp;Ebrahim Falahi ,&nbsp;Fereidoun Azizi","doi":"10.1016/j.jnutbio.2026.110260","DOIUrl":"10.1016/j.jnutbio.2026.110260","url":null,"abstract":"<div><div>Cardiometabolic diseases, including type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) are escalating globally, posing significant health challenges. While dairy products and their bioactive peptides (BPs) may influence chronic diseases risk, the evidence remains inconsistent. These peptides may act via modulation of gut microbiota, reducing inflammation, and regulating lipid metabolism. The current study aimed to investigate the possible association between dairy-derived BPs (DDBPs) and the risk of T2DM and CVDs in Iranian adult population within the framework of Tehran Lipid and Glucose Study (TLGS). In this population-based cohort study, 5,469 participants (T2DM analysis) and 4,980 participants (CVDs analysis) from the TLGS were followed for a mean follow-up period of 6 years. Dietary intake data were determined using a validated food-frequency-questionnaire. Various types of DDBPs were estimated via in-silico proteolysis simulations. The association of bioactive peptides with T2DM and CVDs risk were determined using Cox proportional hazards regression models. Higher intake of k-casein-derived peptides (HR:1.21;95% CI: 1.01–1.64), Hepta-peptides (HR:1.31;95% CI:1.02–1.67), peptides with glycosylated residues (HR:1.29;95%CI: 1.01–1.65), glycosylated residues (HR:1.39;95% CI: 1.07–1.80), and disulfide bond- containing peptides (HR:1.34;95% CI: 1.05–1.71) was associated with an elevated T2DM risk in the adjusted model. Dairy protein intake (highest vs. lowest tertile: HR:1.29;95% CI: 1.02–1.62) Also increased T2DM risk, while total dairy intake showed no association. No significant associations were found between DDBPs, dairy intake, or dairy protein intake and the risk of CVDs. Our results showed that specific DDBPs particularly k-casein-derived fragments and structurally modified peptides (including hepta-peptides, glycosylated peptides, and peptides with disulfide bonds), were associated with an increased risk of T2DM in Tehranian adults. Further studies are warranted to elucidate these associations.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110260"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906260","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":"Mechanism of tea polyphenols improving sleep by regulating neurotransmitters through the gut microbiota–brain axis","authors":"Bin Hu ,&nbsp;Yili Chen ,&nbsp;Xinrong Gong ,&nbsp;Youmeng Chen ,&nbsp;Songmei Luo ,&nbsp;Xin Zhang","doi":"10.1016/j.jnutbio.2026.110272","DOIUrl":"10.1016/j.jnutbio.2026.110272","url":null,"abstract":"<div><div>In today's fast-paced modern lifestyle, sleep disorders have become a pervasive challenge for many individuals. Conventional treatments often rely on pharmacological interventions, which carry risks of dependency and adverse effects. In recent years, the gut microbiota has gained increasing recognition as a \"second brain,\" engaging in bidirectional communication with the central nervous system via the microbiota–gut–brain axis (MGB axis). Tea polyphenols (TP), the primary bioactive compounds derived from tea, show considerable potential in improving sleep quality through this microbial–gut–brain circuitry. This review systematically elucidates how TP reshape the gut microbiota by selectively enriching beneficial bacteria such as <em>Lactobacillus</em> and <em>Bifidobacterium</em>, while suppressing pathogenic species. These structural changes are accompanied by functional benefits, including enhanced intestinal barrier integrity and attenuated systemic inflammation. Furthermore, gut microbiota metabolize TP into bioactive small molecules that enter systemic circulation, cross the blood-brain barrier (BBB), and modulate central neurotransmitters, notably serotonin (5-HT) and γ-aminobutyric acid (GABA). By delineating this gut-mediated neuromodulatory network, our study provides a novel theoretical foundation for the use of TP as a dietary strategy to ameliorate sleep disorders.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110272"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998332","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":"l-Theanine attenuates intestinal oxidative injury in mice through modulation of ferroptosis pathways","authors":"Chunting Shi,&nbsp;Ziyan Yuan,&nbsp;Xinyi Du,&nbsp;Zhiqing Huang,&nbsp;Gang Jia,&nbsp;Hua Zhao,&nbsp;Xiaoling Chen","doi":"10.1016/j.jnutbio.2026.110271","DOIUrl":"10.1016/j.jnutbio.2026.110271","url":null,"abstract":"<div><div>Oxidative stress impairs intestinal health in animals. As a potential antioxidant, <span>l</span>-theanine exerts anti-inflammatory and antioxidant effects. However, its biological functions and underlying mechanisms in intestinal oxidative damage remain unclear. This study aimed to investigate the protective effect of <span>l</span>-theanine against diquat-induced intestinal oxidative damage in mice and explore its potential molecular mechanisms. The results showed that dietary <span>l</span>-theanine supplementation significantly enhanced intestinal antioxidant capacity (reducing the levels of reactive oxygen species, malondialdehyde and hydrogen peroxide and elevating the activities of antioxidant enzymes), alleviated inflammation (downregulating pro-inflammatory cytokine levels and upregulating interleukin-10 mRNA expression), improved intestinal integrity (enhancing morphology, reducing permeability and upregulating tight junction-related genes), and boosted mitochondrial function (increasing mitochondrial membrane potential, adenosine triphosphate content and mitochondrial function-related gene expression) in oxidatively stressed mice. Concomitantly, <span>l</span>-theanine attenuated intestinal iron overload (inhibiting Fe²⁺ accumulation and upregulated ferritin heavy chain 1 expression) and suppressed the ferroptosis pathway (upregulating nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 expression). In conclusion, <span>l</span>-theanine alleviates intestinal oxidative damage in oxidatively stressed mice by enhancing intestinal antioxidant capacity and inhibiting ferroptosis, a protective effect that may be mediated by the activation of the Nrf2/GPX4 signaling pathway.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110271"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003424","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 interaction of ascorbic acid with hemoglobin: Relevance to hemin release and lipid peroxidation","authors":"Shi-Ya Peng,&nbsp;Naihao Lu,&nbsp;Rong Tian","doi":"10.1016/j.jnutbio.2025.110246","DOIUrl":"10.1016/j.jnutbio.2025.110246","url":null,"abstract":"<div><div>The interactions between L-ascorbic acid (<em>i.e.</em>, Vitamin C, VC) and bovine hemoglobin (Hb) were comprehensively analyzed using fluorescence, circular dichroism, UV−vis absorption spectra and molecular docking method, to elucidate the structural mechanisms through which VC altered Hb redox states and stabilities. VC interacted with the central cavities of Hb to form Hb-VC complex via static quenching mechanism involving nonradiative energy transfer, with van der Waals forces and hydrogen bonds playing predominant roles in the binding processes. VC was surrounded by residues such as α1-Thr137, α1-Ser138, α1-Tyr140 and α1-Arg141 residues. After that, the binding of VC would narrow the crevices near the heme domain of Hb, which converted ferric (met-) Hb to ferrous (oxy-) Hb and deoxy-Hb state and suppressed hemin liberation (level of free hemin was 4.35 µM (Hb alone) and 2.77 µM (Hb-VC complex)). Moreover, VC significantly inhibited Hb-catalyzed lipid peroxidation in liposome and washed muscle, which was probably due to the conversion to oxy-Hb state and reduced dissociation of hemin (not free iron). In accordance with its effects on Hb redox states and stability, VC effectively maintained the red color of hemeprotein during the storage. Altogether, the attenuation of free hemin release from Hb molecule represents a new mechanism towards the anti-oxidant capacity of VC in Hb-containing foods.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110246"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846686","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 zinc deficiency regulates the ROS/TLR4/NF-κB pathway to induce pancreatic inflammation and cell death in mice","authors":"Ziyi Li,&nbsp;Yao Xue,&nbsp;Kan Li,&nbsp;Man Qian,&nbsp;Fuhan Wang,&nbsp;Ji-long Luo,&nbsp;Xue-jiao Gao","doi":"10.1016/j.jnutbio.2026.110262","DOIUrl":"10.1016/j.jnutbio.2026.110262","url":null,"abstract":"<div><div>Zinc (Zn) deficiency disrupts redox homeostasis in the body. The pancreas is a vital digestive and endocrine organ of the body, and its normal functional operation cannot proceed without the involvement of Zn. In this study, we established in vivo mouse models, including the normal Zn group (CG, 34 mg Zn/kg), Zn-deficient group (LZn, 2 mg Zn/kg), and Zn-supplemented group (HZn, 100 mg Zn/kg), as well as an in vitro Zn-deficient model of Mouse INsulinoma 6 (MIN6) cells. We systematically investigated the effects of Zn deficiency on pancreatic oxidative stress, inflammation, and cell death. The results showed that Zn deficiency significantly decreased the activities of α-amylase and lipase in the pancreas, and led to pancreatic histological damage. Through flow cytometry and detection of antioxidant enzyme activities, it was found that Zn deficiency induces excessive accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) in the pancreas, and inhibits antioxidant enzyme activities. Using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot, it was observed that Zn deficiency activates the TLR4/NF-κB pathway and significantly increases the expression of the NLRP3 inflammasome and inflammatory factors. Furthermore, Zn deficiency significantly upregulates the expression of apoptosis-related factors (Bax, Caspase-3, Caspase-7, Caspase-9) and necroptosis-related factors (RIPK1, RIPK3, MLKL). Treatment with the antioxidant N-acetylcysteine (NAC) reduces the level of ROS and inhibits the activation of the TLR4/NF-κB pathway, thereby alleviating Zn deficiency-induced inflammation and cell death. Taken together, Zn deficiency induces pancreatic inflammation and cell death by regulating the ROS/TLR4/NF-κB pathway.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110262"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948793","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":"Complex interactions between stress, nutrition, gut microbiota, and infectious diseases and their impact on health in global conflicts: A narrative review","authors":"Pavlo Petakh ,&nbsp;Iryna Halabitska ,&nbsp;Halyna Petrecka ,&nbsp;Wolfgang Huber ,&nbsp;Oleksandr Kamyshnyi","doi":"10.1016/j.jnutbio.2026.110267","DOIUrl":"10.1016/j.jnutbio.2026.110267","url":null,"abstract":"<div><div>Following the global recovery from the COVID-19 pandemic, wars and conflicts have escalated to levels unseen since the Cold War. It is well known that conflict is accompanied not only by significant losses among both military personnel and civilians but also by rising levels of stress and stress-related disorders within the general population. Stress is bidirectionally connected with the state of the gut microbiota through the gut–brain axis. Dietary factors and eating behaviours also play crucial roles in shaping gut microbiota composition. On the one hand, conflict negatively affects food availability and dietary patterns, leading to reduced meal frequency and potentially diminishing microbiota diversity. On the other hand, stress-induced alterations in eating behaviour, such as bulimia or anorexia, can further impair gut microbiota composition. Additionally, individuals in conflict zones face heightened risks of infectious diseases due to disrupted vaccination schedules, poor sanitation, and limited access to clean drinking water. Stress-related immune changes may increase susceptibility to infections and raise the likelihood of adverse outcomes. Moreover, the frequent use of antibiotics to treat infections during conflicts contributes to reduced gut microbiota diversity.</div><div>This review narratively examines the complex interactions among stress, immune responses, dietary patterns, infectious diseases, and gut microbiota in conflict-affected areas, and provides new perspectives on the role of artificial intelligence in modelling such comorbid pathologies.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110267"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994268","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":"Natural products as modulators of ferroptosis: Therapeutic implications and molecular mechanisms in disease treatment","authors":"Weifang Tong ,&nbsp;Xupeng Mu ,&nbsp;Haitao Xu ,&nbsp;Xunzhe Yin","doi":"10.1016/j.jnutbio.2026.110259","DOIUrl":"10.1016/j.jnutbio.2026.110259","url":null,"abstract":"<div><div>Ferroptosis is a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation and is implicated in the pathogenesis of various diseases, including cancer, neurodegenerative disorders, diabetes, and cardiovascular diseases. Natural products, with their unique chemical scaffolds and multitarget pharmacological effects, have recently been recognized as potent modulators of ferroptosis, offering promising drug-like properties. This review comprehensively summarizes the molecular mechanisms underlying ferroptosis, encompassing iron metabolism, lipid peroxidation, and the SLC7A11-GSH-GPX4 antioxidant axis, and systematically categorizes natural products such as terpenoids, flavonoids, alkaloids, saponins, and polyphenols based on their structural classes and mechanisms of action. These compounds modulate ferroptosis through various pathways, including iron chelation, ROS regulation, and key protein interactions, demonstrating efficacy in both experimental and preliminary clinical settings across a spectrum of diseases. In oncology, natural compounds can sensitize tumors to chemotherapy and overcome drug resistance by activating ferroptotic cell death. Conversely, their antiferroptotic actions protect against tissue injury in nononcological diseases such as neurodegenerative conditions, metabolic disorders, and organ injury. Nevertheless, their application remains limited by restricted availability, compositional complexity, and unstable pharmacokinetic features. Advances in nano-delivery systems and synthetic biology are highlighted as promising strategies to overcome these barriers. Overall, natural products represent a valuable resource for developing novel ferroptosis-targeting therapies, with significant implications for future drug discovery and therapeutic innovation in a wide range of human diseases.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110259"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906281","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 naringenin alleviates experimental autoimmune encephalomyelitis in mice partially via estrogen receptor-mediated pathway","authors":"Chaolei Jin ,&nbsp;Qiaozhen Zhu ,&nbsp;Tong Wang ,&nbsp;Zejin Liu ,&nbsp;Hang Wu ,&nbsp;Xinli Niu ,&nbsp;Junpeng Wang","doi":"10.1016/j.jnutbio.2026.110266","DOIUrl":"10.1016/j.jnutbio.2026.110266","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a T-cell-mediated autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination, axonal injury, and loss of oligodendrocytes. Disease severity is influenced by sex hormones, particularly estrogens, which protects against MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, its clinical use is limited by risks such as thrombosis and reproductive tumors. Naringenin, a citrus-derived flavonoid, exhibits anti-inflammatory and neuroprotective properties and has been reported to possess phytoestrogenic activity. In this study, we investigated whether dietary naringenin alleviates autoimmune neuroinflammation in a mouse model of MS with estrogen deficiency induced by ovariectomy. Using a combination of network pharmacology, molecular docking, and <em>in vivo</em> experiments, we examined the effects of naringenin on EAE progression, immune cell responses, cytokine profiles, and estrogen receptor (ESR) signaling. Network pharmacology identified common targets of naringenin, estrogen, and MS, and molecular docking showed stable binding to ESR1. In ovariectomized EAE mice, naringenin attenuated EAE progression via dampening antigen-specific T cell responses, decreasing TNF-α, IL-6, and IL-1β, IFN-γ and IL-17A and increasing anti-inflammatory cytokines IL-10 and TGF-β. Furthermore, naringenin raised serum estradiol and CNS ESRα expression, and its benefits were partially reduced by the ESR antagonist ICI182,780, suggesting ESR signaling contributes to, but does not fully explain, naringenin’s immunomodulatory actions. Overall, these findings demonstrate that dietary naringenin ameliorates autoimmune neuroinflammation in an estrogen-deficient EAE model through mechanisms partially dependent on estrogen receptor signaling, supporting its potential as a dietary or adjunctive strategy for MS.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110266"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994392","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":"Schisandrin B alleviates sulfolane-induced liver injury via the APOA1/ROS/NF-κB signaling pathway","authors":"Yuechen Xing ,&nbsp;Bo Zhang ,&nbsp;Shuo Jin ,&nbsp;Youtong Guo,&nbsp;Yueru Chen,&nbsp;Lili Chen,&nbsp;Yue Wang","doi":"10.1016/j.jnutbio.2025.110255","DOIUrl":"10.1016/j.jnutbio.2025.110255","url":null,"abstract":"<div><div>Sulfolane is a widely used industrial solvent and emerging groundwater contaminant. Sulfolane has hepatotoxicity, but the molecular mechanisms remain poorly understood. Schisandrin B (Sch B), a bioactive lignan isolated from <em>Schisandra chinensis</em>, has been shown to exert hepatoprotective effects. To elucidate the mechanisms underlying sulfolane-induced liver injury and to determine whether Sch B protects against this toxicity by modulating the APOA1/ROS/NF-κB signaling axis. Male C57BL/6 J mice were administered sulfolane (0, 10, 30 or 300 mg/kg) by oral gavage for 28 d, with or without Sch B (8 mg/kg). Liver injury was assessed using histopathology, serum biochemistry, hepatic lipid deposition, ROS levels, and inflammatory marker expression. Bioinformatic analyses integrating “sulfur compound” and “liver injury” datasets were used to identify candidate pathways. The protective effects of Sch B were investigated through APOA1 gene knockdown, APOA1 overexpression, treatment with the antioxidant NAC, and molecular docking experiments of Sch B with APOA1. Sulfolane caused dose-dependent steatosis, oxidative stress and inflammation in mouse liver and AML12 cells. sulfolane suppressed APOA1, increased ROS and activated NF-κB and downstream cytokines. Sch B restored APOA1 expression, reduced ROS accumulation and NF-κB–dependent cytokine production, and markedly improved biochemical and histological indices of liver injury <em>in vivo</em> and <em>in vitro</em>. Sulfolane-induced hepatotoxicity is mediated by suppression of APOA1 and subsequent activation of the NF-κB signaling pathway in a ROS-dependent manner. Schisandrin B protects the liver against this injury by modulating the APOA1/ROS/NF-κB axis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110255"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878572","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":"Myeloid monoamine oxidase A protects against glucose intolerance, insulin resistance and weight gain in high-fat diet-fed mice by preventing the hyperactivation of macrophages","authors":"Seonwook Kim ,&nbsp;Matthew R. Eber ,&nbsp;Alessandro G. Salerno ,&nbsp;Elena Boudyguina ,&nbsp;Reto Asmis","doi":"10.1016/j.jnutbio.2025.110257","DOIUrl":"10.1016/j.jnutbio.2025.110257","url":null,"abstract":"<div><div>The aim of this study was to determine the role of myeloid monoamine oxidase A (Mao A) in diet-induced obesity (DIO). Ten-week-old male and female LysMCre^tg/tg (CTL) and LysMCre^tg/tgMaoA^fl/fl (Mao A_Myeloid^−/−) mice were fed a high-fat diet for 20 week. Male but not female mice with myeloid Mao A deficiency showed increased weight gain, increased visceral adipose tissue (AT) weight as well as elevated fasting blood glucose and leptin levels. However, both male and female Mao A_Myeloid^−/- mice showed increased insulin resistance of the AT and glucose intolerance. Mao A mRNA levels were reduced by 90% and 94% in bone marrow-derived macrophages (BMDM) from male and female Mao A_Myeloid^−/- mice, respectively, but neither Mao A mRNA expression nor protein levels or Mao A activity in AT were altered by myeloid Mao A deficiency. Targeted gene profiling of M_TNFα+IFNγ and M_IL-4-polarized BMDM from Mao A KO mice and 129S1 strain-matched control mice revealed that Mao A deficiency amplifies the expression of polarization state-specific marker genes in BMDM from male mice but affects only a few selected marker genes in female polarized BMDM. Myeloid Mao A protects male but not female mice from AT inflammation, AT expansion and DIO, possibly by suppressing the polarization of monocyte-derived macrophages recruited into the AT. However, myeloid Mao A deficiency promoted insulin resistance in AT and glucose intolerance in both male and female mice suggesting that macrophage Mao A in other tissues contributes to the maintenance of glucose tolerance and homeostasis.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110257"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900796","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}