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Lipophagy: exploring its association with male reproductive system disorders and investigating potential mechanisms. 脂肪摄食:探讨其与男性生殖系统障碍的关系及其潜在机制。
IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-08 DOI: 10.1080/13813455.2024.2446840
Wanyi Chen, Jin Chen, Ziqiong Cheng, Weilun Chen, Huiping Zhang

Background: Lipid metabolism, one of the three major metabolic processes, plays a crucial role in male fertility, particularly when lipid homeostasis is disrupted. Lipid droplets (LDs), cellular organelles that store lipids primarily in the form of triglycerides and cholesterol esters, serve as central hubs in lipid metabolism.The degradation of LDs is regulated by lipases and lipophagy.

Objective:: This review explores the various forms of lipophagy, its molecular mechanisms, and its critical role in male fertility. Specifically, it examines the association between lipophagy and male infertility, sexual dysfunction, and reproductive cancers.

Methods:: This review synthesizes current research on the molecular pathways regulating lipophagy, focusing on its impact on male reproductive health.

Results:: Lipophagy is essential for maintaining lipid homeostasis in male reproductive tissues. Dysfunction of lipophagy is associated with impaired sperm function, infertility, sexual dysfunction, and an increased risk of reproductive cancers in men.

Conclusion:: Lipophagy plays a pivotal role in regulating lipid metabolism and maintaining male fertility. It may serve as a potential therapeutic target for treating male reproductive disorders.

背景:脂质代谢是三大代谢过程之一,在男性生育能力中起着至关重要的作用,特别是当脂质稳态被破坏时。脂滴(LDs),主要以甘油三酯和胆固醇酯的形式储存脂质的细胞器,在脂质代谢中起中心枢纽作用。LDs的降解受脂肪酶和脂噬调节。目的:本文综述了脂肪吞噬的各种形式、分子机制及其在男性生育中的重要作用。具体来说,它研究了脂肪摄取与男性不育、性功能障碍和生殖癌症之间的关系。方法:本文综述了脂肪摄取调控分子途径的研究现状,重点介绍了脂肪摄取对男性生殖健康的影响。结果:脂肪摄取是维持男性生殖组织脂质稳态所必需的。脂肪摄取功能障碍与男性精子功能受损、不孕症、性功能障碍和生殖癌风险增加有关。结论:脂肪摄取在调节脂肪代谢和维持男性生育能力中起着关键作用。它可能成为治疗男性生殖障碍的潜在治疗靶点。
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引用次数: 0
Saracatinib, a Src kinase inhibitor, enhances the renoprotective effect of metformin and losartan in diabetic nephropathy. Saracatinib是一种Src激酶抑制剂,可增强二甲双胍和氯沙坦对糖尿病肾病的肾保护作用。
IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-07 DOI: 10.1080/13813455.2024.2449404
Suzan A Khodir, Eman M Sweed, Mona A Kora, Nader G Zaki, Ghada S Amer, Omnia Ameen

Objective: This research assesses renoprotective effects of saracatinib (Src) in diabetic nephropathy (DN) and the potential underlying processes.

Materials and methods: Rats were divided into: control, DN, DN + Met + Los, DN + Met + Src, and DN + Met + Los + Src. Rats' ABP, urinary albumin, urinary nephrin, and creatinine clearance were assessed. Blood samples were collected for measuring glycaemic state parameters, renal functions, oxidative stress markers, inflammatory mediators, aldosterone, and lipid profile. Kidneys were extracted for KIM-1 and nephrin gene expression, H&E, Masson's trichrome staining, and immunohistochemical assessment.

Results: Significant increases in ABP, urinary albumin and nephrin, glycaemic measurements, urea, creatinine, aldosterone, inflammatory cytokines, MDA, lipids, renal fibrosis, H scores of VEGF and TGF-β, and renal KIM-1 expression were related to DN. However, there was a significant decrease in creatinine clearance, GSH, and nephrin expression in DN group compared with control group.

Discussion and conclusion: The combination of metformin (Met), losartan (Los), and Src repaired DN alterations. Adding Src to Met and Los is superior to using them alone.

目的:本研究评估saracatinib (Src)在糖尿病肾病(DN)中的肾保护作用及其潜在的潜在过程。材料与方法:将大鼠分为:对照组、DN、DN + Met + Los、DN + Met + Src和DN + Met + Los + Src。测定大鼠ABP、尿白蛋白、尿肾素和肌酐清除率。采集血样,测定血糖状态参数、肾功能、氧化应激标志物、炎症介质、醛固酮和血脂。取肾进行KIM-1和nephrin基因表达、H&E、Masson三色染色和免疫组化评估。结果:ABP、尿白蛋白、尿肾素、血糖、尿素、肌酐、醛固酮、炎症因子、MDA、脂质、肾纤维化、VEGF、TGF-β H评分、肾脏KIM-1表达均与DN相关。然而,与对照组相比,DN组肌酐清除率、GSH和nephrin表达明显降低。讨论与结论:二甲双胍(Met)、氯沙坦(Los)和Src联合治疗可修复DN改变。将Src添加到Met和Los中要优于单独使用它们。
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引用次数: 0
Melatonin improves adverse vascular remodelling and redox homeostasis in monocrotaline-induced pulmonary arterial hypertension. 褪黑素可改善单芥碱诱导的肺动脉高压的不良血管重构和氧化还原稳态。
IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-02 DOI: 10.1080/13813455.2024.2446822
Silvio Tasca, Patrick Türck, Daniela Drosdowski, Cristina Campos Carraro, Adriane Belló-Klein, Alexandre Luz De Castro, Alex Sander Da Rosa Araujo

This study explored the effects of melatonin on cardiac and vascular function, and redox homeostasis in model PAH. Male Wistar rats were divided into: control (CTR), monocrotaline [MCT (60 mg/kg, single dose i.p)], monocrotaline + sildenafil [MCT + SIL (50 mg/kg/day)], and monocrotaline + melatonin [MCT + MEL (10 mg/kg/day)]. This protocol lasted 21 days. Echocardiographic, morphometric, histological, vascular reactivity, and oxidative/nitrosative stress analyses were performed. The reduced diastolic function and AT/ET ratio in the MCT group were partially attenuated by melatonin and sildenafil treatment (p < 0.05). Increased RV hypertrophy and pulmonary congestion were reduced by both treatments (p < 0.05). MCT-induced pulmonary arteriolar muscle layer hypertrophy was also reduced by both treatments (p < 0.05). MCT and MCT + SIL present diminished vasorelaxation as compared to control (p < 0.05). Augmented oxidative/nitrosative stress and reduced glutathione-s-transferase activity in MCT were mitigated by both treatments (p < 0.05). Then, melatonin was as effective as sildenafil against PAH-induced oxidative stress and pathological vascular remodelling.

本研究探讨褪黑素对PAH模型心脏和血管功能以及氧化还原稳态的影响。雄性Wistar大鼠分为:对照组(CTR)、单蔓芥碱[MCT (60 mg/kg,单剂量ig)]、单蔓芥碱+西地那非[MCT + SIL (50 mg/kg/day)]、单蔓芥碱+褪黑素[MCT + MEL (10 mg/kg/day)]。该方案持续21 d。超声心动图、形态学、组织学、血管反应性和氧化/亚硝化应激分析。褪黑素和西地那非治疗可部分减轻MCT组舒张功能降低和AT/ET比率(p p p p p)
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引用次数: 0
Self-paced combined training alleviated oxidative stress, inflammatory responses and hyperlipidaemia in people living with multiple sclerosis: a randomised controlled trial.
IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-30 DOI: 10.1080/13813455.2024.2440346
Sonda Jallouli, Dana Jallouli, Mariem Damak, Choumous Kallel, Salma Sakka, Bedreddine Jaafar, Chokri Mhiri, Giovanni de Marco, Fatma Ayadi, Omar Hammouda

Objective: To examine the effects of self-paced combined high-intensity interval training and resistance training (HIIT-RT) on oxidative stress, inflammation lipid profile and body composition in people with multiple sclerosis (PwMS).

Methods: Twenty-three PwMS were randomly assigned to either a control group (CG, n = 12) or a training group (TG, n = 11). The TG performed a 12-week self-paced HIIT-RT (3 times/week). Biomarkers of oxidative stress, inflammation, lipid profile and cellular damage as well as body composition were assessed pre- and post- intervention.

Results: Comparatively with CG, the TG showed a decrease in advanced oxidation protein products (p = 0.002, Hedges'g (g) = 1.50) and total thiols (p = 0.0011, g = 1.57), as well as an increase in reduced glutathione (p = 0.03, g = 0.98). Neutrophils (p = 0.003, g = 1.38), lymphocytes (p = 0.038, g = 0.92) and low-density lipoprotein cholesterol (p < 0.001, g = 2.14) decreased in TG compared with CG. There was also a decrease in body weight (p = 0.003, g = 1.39), body mass index (p = 0.002, g = 1.45) and fat mass (p = 0.006, g = 1.27) in TG comparatively with CG.

Conclusion: This study revealed the effectiviness of self-paced HIIT-RT in alleviating oxidative stress, inflammatory responses and hyperlipidaemia, as well as in improving body composition in PwMS. This combined training may be recommended to better counteract the damage related to multiple sclerosis.

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引用次数: 0
Boldine reduces left ventricle oxidative stress in isoproterenol-induced adrenergic overload experimental model. Boldine降低异丙肾上腺素诱导的肾上腺素能过载实验模型左心室氧化应激。
IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-22 DOI: 10.1080/13813455.2024.2441363
Elissa Kerli Fernandes, Patrick Türck, Cristina Campos Carraro, Silvio Tasca, Isabel Cristina Teixeira Proença, Victor De Mello Palma, Fernanda Visioli, Iraci Lucena Da Silva Torres, Adriane Belló-Klein, Alexandre Luz De Castro, Alex Sander Da Rosa Araujo

Sustained adrenergic overload in the heart causes maladaptive cardiac remodelling, which involves oxidative stress. Boldine (BOL) has antioxidant activity and represents a novel therapeutic approach. This study explored the cardioprotective role of BOL in adverse left ventricular remodelling induced by isoproterenol. The rats were divided into four groups: control; BOL (25 mg/kg daily); isoproterenol (ISO) (5 mg/kg daily), and ISO + BOL. Morphometric, echocardiographic, and oxidative stress parameters were evaluated. BOL attenuated both cardiac hypertrophy and increased diastolic volume caused by adrenergic overstimulation (P < 0.05). BOL treatment reduced lipid peroxidation induced by ISO (ISO vs. ISO + BOL; P < 0.05), and this effect was associated with increased superoxide dismutase (SOD) (ISO vs. ISO + BOL; P < 0.05) and glutathione-S-transferase levels (GST) (ISO vs. ISO + BOL; P < 0.05). This data suggest that BOL may improve cardiac oxidative stress and attenuate some parameters of adverse cardiac remodelling.

心脏持续的肾上腺素能超负荷导致心脏重构不适应,这涉及氧化应激。Boldine (BOL)具有抗氧化活性,是一种新的治疗方法。本研究探讨了BOL在异丙肾上腺素诱导的不良左心室重构中的心脏保护作用。将大鼠分为四组:对照组;BOL(每日25毫克/公斤);异丙肾上腺素(ISO)(每天5mg /kg)和ISO + BOL。评估形态学、超声心动图和氧化应激参数。BOL减轻了肾上腺素能过度刺激引起的心脏肥大和舒张容积增加(P
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引用次数: 0
The oral microbial odyssey influencing chronic metabolic disease. 影响慢性代谢性疾病的口腔微生物奥德赛。
IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 Epub Date: 2023-12-25 DOI: 10.1080/13813455.2023.2296346
Upasana Gupta, Priyankar Dey

Introduction: Since the oral cavity is the gateway to the gut, oral microbes likely hold the potential to influence metabolic disease by affecting the gut microbiota.

Method: A thorough review of literature has been performed to link the alterations in oral microbiota with chronic metabolic disease by influencing the gut microbiota.

Result: A strong correlation exists between abnormalities in oral microbiota and several systemic disorders, such as cardiovascular disease, diabetes, and obesity, which likely initially manifest as oral diseases. Ensuring adequate oral hygiene practices and cultivating diverse oral microflora are crucial for the preservation of general well-being. Oral bacteria have the ability to establish and endure in the gastrointestinal tract, leading to the development of prolonged inflammation and activation of the immune system. Oral microbe-associated prophylactic strategies could be beneficial in mitigating metabolic diseases.

Conclusion: Oral microbiota can have a profound impact on the gut microbiota and influence the pathogenesis of metabolic diseases.

简介:由于口腔是通往肠道的门户,口腔微生物可能会通过影响肠道微生物群来影响代谢性疾病:由于口腔是通往肠道的门户,口腔微生物很可能通过影响肠道微生物群而影响代谢性疾病:方法:我们对文献进行了全面回顾,通过影响肠道微生物群,将口腔微生物群的改变与慢性代谢性疾病联系起来:结果:口腔微生物群异常与心血管疾病、糖尿病和肥胖症等多种全身性疾病之间存在密切联系,而这些疾病最初很可能表现为口腔疾病。确保适当的口腔卫生习惯和培养多样化的口腔微生物菌群对维护整体健康至关重要。口腔细菌有能力在胃肠道中建立和存活,导致长期炎症和免疫系统激活。与口腔微生物相关的预防性策略有助于缓解代谢性疾病:口腔微生物群可对肠道微生物群产生深远影响,并影响代谢性疾病的发病机制。
{"title":"The oral microbial odyssey influencing chronic metabolic disease.","authors":"Upasana Gupta, Priyankar Dey","doi":"10.1080/13813455.2023.2296346","DOIUrl":"10.1080/13813455.2023.2296346","url":null,"abstract":"<p><strong>Introduction: </strong>Since the oral cavity is the gateway to the gut, oral microbes likely hold the potential to influence metabolic disease by affecting the gut microbiota.</p><p><strong>Method: </strong>A thorough review of literature has been performed to link the alterations in oral microbiota with chronic metabolic disease by influencing the gut microbiota.</p><p><strong>Result: </strong>A strong correlation exists between abnormalities in oral microbiota and several systemic disorders, such as cardiovascular disease, diabetes, and obesity, which likely initially manifest as oral diseases. Ensuring adequate oral hygiene practices and cultivating diverse oral microflora are crucial for the preservation of general well-being. Oral bacteria have the ability to establish and endure in the gastrointestinal tract, leading to the development of prolonged inflammation and activation of the immune system. Oral microbe-associated prophylactic strategies could be beneficial in mitigating metabolic diseases.</p><p><strong>Conclusion: </strong>Oral microbiota can have a profound impact on the gut microbiota and influence the pathogenesis of metabolic diseases.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"831-847"},"PeriodicalIF":2.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The triggering pathway, the metabolic amplifying pathway, and cellular transduction in regulation of glucose-dependent biphasic insulin secretion. 调节葡萄糖依赖性双相胰岛素分泌的触发途径、代谢放大途径和细胞传导。
IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 Epub Date: 2024-01-09 DOI: 10.1080/13813455.2023.2299920
Shradha Bisht, Mamta F Singh

Introduction: Insulin secretion is a highly regulated process critical for maintaining glucose homeostasis. This abstract explores the intricate interplay between three essential pathways: The Triggering Pathway, The Metabolic Amplifying Pathway, and Cellular Transduction, in orchestrating glucose-dependent biphasic insulin secretion.

Mechanism: During the triggering pathway, glucose metabolism in pancreatic beta-cells leads to ATP production, closing ATP-sensitive potassium channels and initiating insulin exocytosis. The metabolic amplifying pathway enhances insulin secretion via key metabolites like NADH and glutamate, enhancing calcium influx and insulin granule exocytosis. Additionally, the cellular transduction pathway involves G-protein coupled receptors and cyclic AMP, modulating insulin secretion.

Result and conclusion: These interconnected pathways ensure a dynamic insulin response to fluctuating glucose levels, with the initial rapid phase and the subsequent sustained phase. Understanding these pathways' complexities provides crucial insights into insulin dysregulation in diabetes and highlights potential therapeutic targets to restore glucose-dependent insulin secretion.

导言胰岛素分泌是一个高度调节的过程,对维持葡萄糖稳态至关重要。本摘要探讨了三种重要途径之间错综复杂的相互作用:触发途径、代谢放大途径和细胞传导在协调葡萄糖依赖性双相胰岛素分泌过程中的作用机制:在触发途径中,胰岛β细胞内的葡萄糖代谢会产生 ATP,关闭 ATP 敏感性钾通道,启动胰岛素外渗。代谢放大途径通过 NADH 和谷氨酸等关键代谢物增强胰岛素分泌,促进钙离子流入和胰岛素颗粒外渗。此外,细胞传导途径涉及 G 蛋白偶联受体和环磷酸腺苷,可调节胰岛素分泌:这些相互关联的途径确保了胰岛素对波动的葡萄糖水平做出动态反应,包括最初的快速阶段和随后的持续阶段。了解这些通路的复杂性有助于深入了解糖尿病患者的胰岛素失调,并突出了恢复葡萄糖依赖性胰岛素分泌的潜在治疗靶点。
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引用次数: 0
Andrographis paniculata (Burm. f.) Nees extract ameliorates insulin resistance in the insulin-resistant HepG2 cells via GLUT2/IRS-1 pathway. 穿心莲f。)Nees提取物通过GLUT2/IRS-1通路改善胰岛素抵抗HepG2细胞的胰岛素抵抗。
IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 Epub Date: 2023-10-25 DOI: 10.1080/13813455.2023.2273221
Sri Ningsih, Siska Andrina Kusumastuti, Nuralih Nuralih, Adam Arditya Fajriawan, Devi Permatasari, Prasetyawan Yunianto, Donny Ramadhan, Mayriska Tri Wulandari, Nisrina Firdausi, Nurhadi Nurhadi, Reni Giarni, Kurnia Agustini, Agung Eru Wibowo, Idah Rosidah, Tiya Novlita Rengganis, Ngatinem Ngatinem, Agus Himawan Subiantoro, Agus Supriyono

Hyperglycaemia is one condition related to inflammation leading to insulin signalling impairment. This study was conducted to investigate the insulin sensitivity improvement of Sambiloto (Andrographis paniculata (Burm. f.)) Nees extract in insulin resistance-induced HepG2 (IR-HepG2) cells by stimulating insulin sensitivities and inhibiting inflammatory response. Sambiloto extract at 2 µg/mL revealed glucose uptake stimulation and up-regulating GLUT-2 and IRS-1 gene expression, and inhibited pro-inflammatory cytokine IL-6 gene expression in IR-HepG2 cells. Phytochemical analysis showed that the total phenolic level and andrografolide content of Sambiloto extract were 2.91 ± 0.04% and 1.95%, respectively. This result indicated that Sambiloto extract ameliorated insulin resistance in high glucose-induced IR-HepG2 cells via modulating the IRS-1/GLUT-2 pathway due to IL-6 inhibition. These findings suggested that Sambiloto extract had potency as an anti-inflammatory and insulin-resistance improvement in IR-HepG2 cells.

高血糖是一种与炎症相关的疾病,导致胰岛素信号受损。本研究旨在通过刺激胰岛素敏感性和抑制炎症反应来研究三倍子提取物对胰岛素抵抗诱导的HepG2(IR-HepG2)细胞的胰岛素敏感性的改善作用。桑比洛托提取物2 µg/mL在IR-HepG2细胞中显示葡萄糖摄取刺激和上调GLUT-2和IRS-1基因表达,并抑制促炎细胞因子IL-6基因表达。植物化学分析表明,桑比洛提取物的总酚含量和穿心莲内酯含量分别为2.91 ± 分别为0.04%和1.95%。这一结果表明,桑比洛提取物通过调节由于IL-6抑制而引起的IRS-1/GUT-2途径,改善了高糖诱导的IR-HepG2细胞中的胰岛素抵抗。这些发现表明桑比洛托提取物在IR-HepG2细胞中具有抗炎和胰岛素抵抗改善作用。
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引用次数: 0
Berberine-induced glucagon-like peptide-1 and its mechanism for controlling type 2 diabetes mellitus: a comprehensive pathway review. 黄连素诱导的胰高血糖素样肽-1及其控制2型糖尿病的机制:综合途径综述。
IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 Epub Date: 2023-11-03 DOI: 10.1080/13813455.2023.2258559
Mostafa Araj-Khodaei, Mohammad Hossein Ayati, Akbar Azizi Zeinalhajlou, Tannaz Novinbahador, Mehdi Yousefi, Mahdi Shiri, Ata Mahmoodpoor, Ali Shamekh, Nazli Namazi, Sarvin Sanaie

Introduction: A growing number of studies have thus far showed the association between type 2 diabetes mellitus (DM) and the intestinal microbiome homoeostasis. As reported, the gut microflora can be significantly different in patients with type 2 DM (T2DM) compared to those in healthy individuals.

Methods: The authors collected the relevant articles published until 2022 and these are carefully selected from three scientific databases based on keywords.

Discussion: This review highlights research on the anti-diabetic properties of berberine (BBR)-induced glucagon-like peptide-1 (GLP-1), as a glucose-lowering factor and a balance regulator in the microbial flora of the intestines, which plays an important role in adjusting the signalling pathways affecting insulin secretion.

Results: Considering the anti-diabetic characteristics of the BBR-induced GLP-1, BBR makes a promising complementary treatment for reducing the clinical symptoms of DM by reducing the hyperglycaemia. Berberin might be a safe and effective drug for T2DM with little or no adverse effects.

引言:到目前为止,越来越多的研究表明2型糖尿病(DM)与肠道微生物组稳态之间存在关联。据报道,2型患者的肠道菌群可能存在显著差异 DM(T2DM)与健康个体相比。方法:作者收集了截至2022年发表的相关文章,并根据关键词从三个科学数据库中仔细挑选。讨论:这篇综述重点研究了黄连素(BBR)诱导的胰高血糖素样肽-1(GLP-1)的抗糖尿病特性,GLP-1是一种降血糖因子和肠道微生物群中的平衡调节因子,在调节影响胰岛素分泌的信号通路中起着重要作用。结果:考虑到BBR诱导的GLP-1的抗糖尿病特性,BBR通过降低高血糖来减少糖尿病的临床症状,是一种很有前途的补充治疗方法。柏培林可能是一种安全有效的治疗T2DM的药物,不良反应很少或没有。提示:黄连素在肠道中通过PLC2途径诱导GLP-1胰岛素分泌黄连素诱导的GLP-1降低线粒体应激并将细胞色素c从线粒体中重新定位。黄连素通过改变细菌特性诱导肠内GLP-1分泌,从而可能减轻糖尿病症状。黄连素诱导的SCFA产生,SCFA导致肠L细胞分泌GLP-1。因此,防止线粒体损伤、减少脂肪组织脂肪和减少氧化应激是BBR诱导的GLP-1的结果之一,其有限的副作用和较高的可用性使其成为治疗糖尿病的一种有前途的辅助药物。
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引用次数: 0
Bisphenol A induces non-alcoholic fatty liver disease by promoting the O-GlcNAcylation of NLRP3. 双酚A通过促进NLRP3的o - glcn酰化诱导非酒精性脂肪肝。
IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-12-01 Epub Date: 2023-12-01 DOI: 10.1080/13813455.2023.2288533
Yonghong Zhang, Shujuan Han, Tian Li, Li Zhu, Feng Wei

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. The mechanism by which bisphenol A (BPA) promots NAFLD remains unclear. Palmitic acid (PA) and lipopolysaccharide (LPS) were used to simulate NAFLD in HepG2 cells in vitro. Total cholesterol (TC), triglyceride (TG) content, and lipid accumulation were measured to evaluate lipid metabolism. The caspase-1-stained cells and NLRP3 inflammasome-associated proteins were evaluated for pyroptosis. Western blot analysis was used to detect protein levels and co-immunoprecipitation (Co-IP) was used to detect the association between the proteins. Cycloheximide (CHX) treatment combined with western blot was performed to access protein stability. This data have shown that BPA induces lipid metabolism dysfunction and pyroptosis by upregulating O-GlcNAc transferase (OGT) level. NLRP3 directly interacts with OGT, and elevated OGT enhanced the stability of NLRP3 protein. BPA promoted OGT-mediated O-GlcNAcylation to stabilised NLRP3, thus accelerating NAFLD progress in vitro. Our study reveals that BPA, as an environmental factor, may be involved in the promotion of NAFLD, and that targeting NLRP3 and OGT may inhibit BPA's induction of NAFLD.

非酒精性脂肪性肝病(NAFLD)是最常见的肝病。双酚A (BPA)促进NAFLD的机制尚不清楚。采用棕榈酸(PA)和脂多糖(LPS)体外模拟HepG2细胞NAFLD。测定总胆固醇(TC)、甘油三酯(TG)含量和脂质积累来评估脂质代谢。观察caspase-1染色的细胞和NLRP3炎性小体相关蛋白是否存在焦亡。Western blot法检测蛋白水平,Co-IP法检测蛋白之间的相关性。环己亚胺(CHX)联合western blot检测蛋白稳定性。这些数据表明BPA通过上调O-GlcNAc转移酶(OGT)水平诱导脂质代谢功能障碍和焦亡。NLRP3直接与OGT相互作用,升高的OGT增强了NLRP3蛋白的稳定性。BPA促进ogt介导的o - glcn酰化以稳定NLRP3,从而加速体外NAFLD的进展。我们的研究表明BPA作为一种环境因素可能参与了NAFLD的促进,靶向NLRP3和OGT可能抑制BPA对NAFLD的诱导。
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引用次数: 0
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