Journal of Nutritional Biochemistry最新文献_第9页

Erucic acid, eicosapentaenoic acid, and docosahexaenoic acid consumption affect hepatic steatosis in mice fed a western diet 芥酸、二十碳五烯酸和二十二碳六烯酸的摄入对饲喂西方饮食的小鼠肝脏脂肪变性有影响。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-12 DOI: 10.1016/j.jnutbio.2025.110183

Lene S. Myrmel , Stine Hoff Austgulen , Annette Bernhard , Atabak M. Azad , Even Fjære

This study explored whether erucic acid (EA) intake at levels typical of fatty fish consumption aggravates non-alcoholic fatty liver disease (NAFLD) or affects the benefits of marine n-3 polyunsaturated fatty acids (PUFAs). N-3 PUFAs, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), enhance beta-oxidation and suppress lipogenesis, reducing hepatic triglyceride accumulation.

Sixty-six C57BL/6N mice were fed a chow diet, western diet (WD), or WDs supplemented with EA alone or combined with EPA or DHA for 13 weeks. Dietary EA, EPA, and DHA levels matched average intake from recommended fatty fish consumption. Body weight and food intake were monitored, followed by body composition scans and glucose tolerance testing (GTT). After the feeding trial, hepatic lipid accumulation was analyzed.

EA supplementation did not increase hepatic fat or worsen WD-induced hepatic steatosis. Dietary intake of EPA together with EA preserved protection against elevated liver fat. EA alone reduced glucose tolerance, while fasting glucose was unchanged. However, intake of EA combined with EPA or DHA also elevated fasting and post-glucose blood glucose levels.

In conclusion, EA at levels relevant to fatty fish consumption does not impact hepatic steatosis. And EPA combined with EA prevented liver fat buildup. However, EA alone and in combination with EPA or DHA reduced glucose tolerance, assessed by the area under the curve during the glucose tolerance test, highlighting potential metabolic concerns and the need for further study the role of EA in glucose metabolism.

本研究探讨了典型的脂肪鱼摄入水平下的芥酸（EA）是否会加重非酒精性脂肪性肝病（NAFLD）或影响海洋n-3多不饱和脂肪酸（PUFAs）的益处。n-3 PUFAs，特别是二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），促进β -氧化和抑制脂肪生成，减少肝脏甘油三酯的积累。66只C57BL/6N小鼠分别饲喂鼠粮、西粮、西粮中单独添加EA或与EPA或DHA联合添加EA的西粮，为期13周。饮食中EA， EPA和DHA的水平与推荐的脂肪鱼的平均摄入量相符。监测体重和食物摄入量，随后进行身体成分扫描和葡萄糖耐量测试（GTT）。饲喂试验结束后，分析肝脏脂质积累情况。补充EA不会增加肝脏脂肪或加重wd诱导的肝脂肪变性。膳食摄入EPA和EA可以防止肝脏脂肪升高。单独服用EA可降低葡萄糖耐量，而空腹血糖不变。然而，EA与EPA或DHA联合摄入也会提高空腹和葡萄糖后血糖水平。综上所述，与脂肪鱼摄取量相关的EA水平不会影响肝脏脂肪变性。EPA和EA联合使用可以防止肝脏脂肪堆积。然而，在葡萄糖耐量试验中，通过曲线下面积评估，EA单独使用以及与EPA或DHA联合使用均降低了葡萄糖耐量，这突出了潜在的代谢问题，需要进一步研究EA在葡萄糖代谢中的作用。

{"title":"Erucic acid, eicosapentaenoic acid, and docosahexaenoic acid consumption affect hepatic steatosis in mice fed a western diet","authors":"Lene S. Myrmel , Stine Hoff Austgulen , Annette Bernhard , Atabak M. Azad , Even Fjære","doi":"10.1016/j.jnutbio.2025.110183","DOIUrl":"10.1016/j.jnutbio.2025.110183","url":null,"abstract":"<div><div>This study explored whether erucic acid (EA) intake at levels typical of fatty fish consumption aggravates non-alcoholic fatty liver disease (NAFLD) or affects the benefits of marine n-3 polyunsaturated fatty acids (PUFAs). N-3 PUFAs, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), enhance beta-oxidation and suppress lipogenesis, reducing hepatic triglyceride accumulation.</div><div>Sixty-six C57BL/6N mice were fed a chow diet, western diet (WD), or WDs supplemented with EA alone or combined with EPA or DHA for 13 weeks. Dietary EA, EPA, and DHA levels matched average intake from recommended fatty fish consumption. Body weight and food intake were monitored, followed by body composition scans and glucose tolerance testing (GTT). After the feeding trial, hepatic lipid accumulation was analyzed.</div><div>EA supplementation did not increase hepatic fat or worsen WD-induced hepatic steatosis. Dietary intake of EPA together with EA preserved protection against elevated liver fat. EA alone reduced glucose tolerance, while fasting glucose was unchanged. However, intake of EA combined with EPA or DHA also elevated fasting and post-glucose blood glucose levels.</div><div>In conclusion, EA at levels relevant to fatty fish consumption does not impact hepatic steatosis. And EPA combined with EA prevented liver fat buildup. However, EA alone and in combination with EPA or DHA reduced glucose tolerance, assessed by the area under the curve during the glucose tolerance test, highlighting potential metabolic concerns and the need for further study the role of EA in glucose metabolism.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110183"},"PeriodicalIF":4.9,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523650","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}

引用次数: 0

Protective effects of pyrroloquinoline quinone in CNS disorders 吡咯喹啉醌对中枢神经系统疾病的保护作用。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-12 DOI: 10.1016/j.jnutbio.2025.110178

Sara Aboulhassane , Vishal Sangha , Reina Bendayan

Pyrroloquinoline quinone (PQQ) is an enzyme belonging to the family of quinone cofactors (or quinoproteins) naturally found in soil and food. PQQ was initially discovered as an essential cofactor for bacterial dehydrogenases and has since been reported to be involved in several biological processes important for mammalian growth and development. Animal studies have demonstrated that insufficient dietary intake of PQQ can lead to notable deficits, including impaired growth and compromised reproductive outcomes. In more recent years, PQQ has been recognized for its neuroprotective effects in several in vitro and in vivo models of brain injury and disease, rendering it an attractive compound to be incorporated into treatment strategies for various neurological disorders. More specifically, PQQ has been reported to enhance mitochondrial function and mitigate inflammatory and oxidative stress responses in the central nervous system (CNS) through the activation of several signaling pathways. Additionally, PQQ has emerged as a promising compound that could be incorporated in treatment strategies for cerebral folate deficiency, a pediatric neurological condition characterized by suboptimal folate levels in the cerebrospinal fluid, leading to developmental delays, epilepsy, and other neurological symptoms. This review will address the biochemical properties, mechanism of action, and physiological roles of PQQ with a specific focus on its antioxidant and anti-inflammatory effects as well as its role in enhancing mitochondrial function. The therapeutic implications of these findings will be discussed, emphasizing PQQ’s potential as a novel pharmacological approach for the management of neurological disorders, including its emerging role in cerebral folate deficiency.

吡咯喹啉醌（PQQ）是一种天然存在于土壤和食物中的醌辅助因子（或醌蛋白）家族的酶。PQQ最初被发现是细菌脱氢酶的重要辅助因子，并被报道参与了哺乳动物生长发育的几个重要生物过程。动物研究表明，膳食中PQQ摄入不足会导致显著的缺陷，包括生长受损和生殖结果受损。近年来，PQQ在一些脑损伤和疾病的体外和体内模型中被认为具有神经保护作用，使其成为一种有吸引力的化合物，可以纳入各种神经系统疾病的治疗策略。更具体地说，PQQ已被报道通过激活几种信号通路增强线粒体功能，减轻中枢神经系统（CNS）的炎症和氧化应激反应。此外，PQQ已成为一种有前景的化合物，可纳入脑叶酸缺乏症的治疗策略。脑叶酸缺乏症是一种小儿神经系统疾病，其特征是脑脊液中叶酸水平低于理想水平，导致发育迟缓、癫痫和其他神经系统症状。本文将对PQQ的生化特性、作用机制和生理作用进行综述，重点介绍其抗氧化和抗炎作用以及增强线粒体功能的作用。这些发现的治疗意义将被讨论，强调PQQ作为一种治疗神经系统疾病的新药理学方法的潜力，包括它在脑叶酸缺乏症中的新作用。

{"title":"Protective effects of pyrroloquinoline quinone in CNS disorders","authors":"Sara Aboulhassane , Vishal Sangha , Reina Bendayan","doi":"10.1016/j.jnutbio.2025.110178","DOIUrl":"10.1016/j.jnutbio.2025.110178","url":null,"abstract":"<div><div>Pyrroloquinoline quinone (PQQ) is an enzyme belonging to the family of quinone cofactors (or quinoproteins) naturally found in soil and food. PQQ was initially discovered as an essential cofactor for bacterial dehydrogenases and has since been reported to be involved in several biological processes important for mammalian growth and development. Animal studies have demonstrated that insufficient dietary intake of PQQ can lead to notable deficits, including impaired growth and compromised reproductive outcomes. In more recent years, PQQ has been recognized for its neuroprotective effects in several <em>in vitro</em> and <em>in vivo</em> models of brain injury and disease, rendering it an attractive compound to be incorporated into treatment strategies for various neurological disorders. More specifically, PQQ has been reported to enhance mitochondrial function and mitigate inflammatory and oxidative stress responses in the central nervous system (CNS) through the activation of several signaling pathways. Additionally, PQQ has emerged as a promising compound that could be incorporated in treatment strategies for cerebral folate deficiency, a pediatric neurological condition characterized by suboptimal folate levels in the cerebrospinal fluid, leading to developmental delays, epilepsy, and other neurological symptoms. This review will address the biochemical properties, mechanism of action, and physiological roles of PQQ with a specific focus on its antioxidant and anti-inflammatory effects as well as its role in enhancing mitochondrial function. The therapeutic implications of these findings will be discussed, emphasizing PQQ’s potential as a novel pharmacological approach for the management of neurological disorders, including its emerging role in cerebral folate deficiency.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110178"},"PeriodicalIF":4.9,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523686","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}

引用次数: 0

Composition, function, and detection methods of the intestinal barrier 肠屏障的组成、功能和检测方法。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-11 DOI: 10.1016/j.jnutbio.2025.110179

Nannan Sun , Wenyu Liu , Jing Li , Dandan Zhang , Xiuli Liu , Juan Liu , Huiling Hu

The intestinal barrier represents a fundamental defense system against environmental insults, and its disruption is increasingly recognized as a central contributor to the pathogenesis of diverse diseases. This review provides a comprehensive analysis of intestinal barrier function, highlighting its pivotal role in maintaining physiological homeostasis. We delineate the structural components and regulatory mechanisms that safeguard barrier integrity, and examine the factors that precipitate barrier dysfunction and their implications for disease progression. Particular emphasis is placed on the gut-brain, gut-eye, and gut-liver axes, which mediate the systemic consequences of barrier impairment on overall health. Additionally, we critically evaluate current methodologies for assessing intestinal barrier integrity, discussing their respective advantages and limitations. By synthesizing these insights, this review aims to guide the selection of appropriate investigative approaches, thereby facilitating advancements in disease prevention and therapeutic strategies. Ultimately, this work seeks to deepen understanding of intestinal barrier dynamics and to inform future directions in this rapidly evolving field.

肠道屏障是抵御环境侵害的基本防御系统，它的破坏越来越被认为是多种疾病发病机制的核心因素。本文综述了肠道屏障功能的全面分析，强调了其在维持生理稳态中的关键作用。我们描述了保护屏障完整性的结构成分和调节机制，并研究了导致屏障功能障碍的因素及其对疾病进展的影响。特别强调的是肠-脑、肠-眼和肠-肝轴，它们介导了屏障损伤对整体健康的系统性后果。此外，我们批判性地评估目前评估肠道屏障完整性的方法，讨论各自的优点和局限性。通过综合这些见解，本综述旨在指导选择适当的研究方法，从而促进疾病预防和治疗策略的进步。最终，这项工作旨在加深对肠道屏障动力学的理解，并为这一快速发展领域的未来方向提供信息。

{"title":"Composition, function, and detection methods of the intestinal barrier","authors":"Nannan Sun , Wenyu Liu , Jing Li , Dandan Zhang , Xiuli Liu , Juan Liu , Huiling Hu","doi":"10.1016/j.jnutbio.2025.110179","DOIUrl":"10.1016/j.jnutbio.2025.110179","url":null,"abstract":"<div><div>The intestinal barrier represents a fundamental defense system against environmental insults, and its disruption is increasingly recognized as a central contributor to the pathogenesis of diverse diseases. This review provides a comprehensive analysis of intestinal barrier function, highlighting its pivotal role in maintaining physiological homeostasis. We delineate the structural components and regulatory mechanisms that safeguard barrier integrity, and examine the factors that precipitate barrier dysfunction and their implications for disease progression. Particular emphasis is placed on the gut-brain, gut-eye, and gut-liver axes, which mediate the systemic consequences of barrier impairment on overall health. Additionally, we critically evaluate current methodologies for assessing intestinal barrier integrity, discussing their respective advantages and limitations. By synthesizing these insights, this review aims to guide the selection of appropriate investigative approaches, thereby facilitating advancements in disease prevention and therapeutic strategies. Ultimately, this work seeks to deepen understanding of intestinal barrier dynamics and to inform future directions in this rapidly evolving field.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110179"},"PeriodicalIF":4.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513171","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}

引用次数: 0

Maternal carbohydrate-programming enhances carbohydrate utilization in zebrafish offspring by histone H3K9 methylation 母体碳水化合物编程通过组蛋白H3K9甲基化提高斑马鱼后代对碳水化合物的利用。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-11 DOI: 10.1016/j.jnutbio.2025.110184

Zi-Jun Hu , Jun-Jie You , Yun-Liang Miao , Hong-Liang Lu , Jia-Ming Zou , Ling Li , Shan He

Accompanied by the increased intake of carbohydrate-rich foods, the utilization of carbohydrate is enhanced across generations of humans, but little is known about its epigenetic mechanism. In this study, zebrafish fed with carbohydrate-rich diets for two months (carbohydrate-programming group, PG), showed the better utilization of carbohydrates than those fed with carbohydrate-normal diets (normal group, NG) in the first and the second high-carbohydrate diet challenge, including the preference for ingesting glucose, and the enhanced carbohydrate absorption and metabolism. The maternal zebrafish were mated with wild type males, and the utilization of carbohydrates was also improved in the offspring from the PG. Through RNA-seq and ATAC-seq of offspring, beside of the higher expression of glut2 gene related to glucose absorption and phip gene related to carbohydrate metabolism, the mRNA level of H3K9me2-specific histone methyltransferase gene ehmt2 was down-regulated, while the demethylase gene kdm4a was significantly up-regulated, and then the protein levels of H3K9me2 was decreased in the PG. Furthermore, the regulatory relationship of H3K9me2 with glut2 and phip was demonstrated by the treatment with the ehmt2 inhibitor BRD4770 in vitro, administration of the kdm4a inhibitor PKF-118-310 in vivo, combining with the methods of dual-luciferase, ChIP and siRNA. Therefore, the improved carbohydrate utilization induced by maternal programming could be inherited through epigenetics, provide new insights into human dietary nutrition plans and therapeutic targets for diabetes.

随着富含碳水化合物食物摄入量的增加，人类对碳水化合物的利用在几代人之间增强，但对其表观遗传机制知之甚少。在本研究中，饲喂高碳水化合物饮食两个月的斑马鱼（碳水化合物计划组，PG）在第一次和第二次高碳水化合物饮食挑战中表现出比饲喂碳水化合物正常饮食（正常组，NG）的斑马鱼更好的碳水化合物利用，包括对摄取葡萄糖的偏好，以及碳水化合物的吸收和代谢增强。将母代斑马鱼与野生型雄鱼交配，后代对碳水化合物的利用也得到了提高，通过后代的RNA-seq和ATAC-seq分析，除了葡萄糖吸收相关的glut2基因和碳水化合物代谢相关的phip基因的高表达外，h3k9me2特异性组蛋白甲基转移酶基因ehmt2的mRNA水平下调，而去甲基化酶基因kdm4a的mRNA水平显著上调。在体外用ehmt2抑制剂BRD4770处理，体内用kdm4a抑制剂PKF-118-310处理，结合双荧光素酶、ChIP和siRNA的方法，研究H3K9me2与glut2和phip的调控关系。因此，母体编程诱导的碳水化合物利用的改善可以通过表观遗传学的方式遗传，为人类饮食营养计划和糖尿病的治疗靶点提供新的见解。

{"title":"Maternal carbohydrate-programming enhances carbohydrate utilization in zebrafish offspring by histone H3K9 methylation","authors":"Zi-Jun Hu , Jun-Jie You , Yun-Liang Miao , Hong-Liang Lu , Jia-Ming Zou , Ling Li , Shan He","doi":"10.1016/j.jnutbio.2025.110184","DOIUrl":"10.1016/j.jnutbio.2025.110184","url":null,"abstract":"<div><div>Accompanied by the increased intake of carbohydrate-rich foods, the utilization of carbohydrate is enhanced across generations of humans, but little is known about its epigenetic mechanism. In this study, zebrafish fed with carbohydrate-rich diets for two months (carbohydrate-programming group, PG), showed the better utilization of carbohydrates than those fed with carbohydrate-normal diets (normal group, NG) in the first and the second high-carbohydrate diet challenge, including the preference for ingesting glucose, and the enhanced carbohydrate absorption and metabolism. The maternal zebrafish were mated with wild type males, and the utilization of carbohydrates was also improved in the offspring from the PG. Through RNA-seq and ATAC-seq of offspring, beside of the higher expression of <em>glut2</em> gene related to glucose absorption and <em>phip</em> gene related to carbohydrate metabolism, the mRNA level of H3K9me2-specific histone methyltransferase gene <em>ehmt2</em> was down-regulated, while the demethylase gene <em>kdm4a</em> was significantly up-regulated, and then the protein levels of H3K9me2 was decreased in the PG. Furthermore, the regulatory relationship of H3K9me2 with <em>glut2</em> and <em>phip</em> was demonstrated by the treatment with the <em>ehmt2</em> inhibitor BRD4770 <em>in vitro</em>, administration of the <em>kdm4a</em> inhibitor PKF-118-310 <em>in vivo</em>, combining with the methods of dual-luciferase, ChIP and siRNA. Therefore, the improved carbohydrate utilization induced by maternal programming could be inherited through epigenetics, provide new insights into human dietary nutrition plans and therapeutic targets for diabetes.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110184"},"PeriodicalIF":4.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513216","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}

引用次数: 0

Bidirectional regulation of free fatty acid receptors and non-alcoholic fatty liver disease 游离脂肪酸受体与非酒精性脂肪肝的双向调节。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-10 DOI: 10.1016/j.jnutbio.2025.110180

Yiyu Lin , Yanglong Liu , Jianshen Liu , Jianxing Wu , Kunhua Wei , Jiao Guo , Zhengquan Su

Free fatty acid receptor action is primarily in the area of energy modulation and maintenance of normal metabolism in the body. They have been identified and attributed to specific G protein-coupled receptors (GPCRs). Currently, the main findings include four receptors: FFAR1 to FFAR4. Free fatty acids (FFAs) with different carbon chain lengths respond to different FFAR. Short-chain fatty acids (C2-C6) bind specifically to FFAR2 and FFAR3, whereas medium-chain fatty acids (C6-C12) and long-chain fatty acids (C13-C21) target both FFAR1 and FFAR4. FFARs have been considered as potential target for the treatment of common metabolic diseases such as T2M, cardiovascular diseases and inflammatory bowel diseases. Nonalcoholic fatty liver disease is a common metabolic disorder and is often accompanied by various metabolic and cardiovascular diseases. The expression and modulation of FFARs in the body may be related to the development of nonalcoholic fatty liver disease. This article introduces the source, synthesis and metabolic pathways of fatty acids, and comprehensively summarizes the research on FFARs signal transduction and its physiological functions, the regulation between FFARs and NAFLD, and the prospect of FFARs-based treatment of NAFLD.

游离脂肪酸受体的作用主要是在能量调节和维持机体正常代谢方面。它们已被鉴定并归因于特异性G蛋白偶联受体（gpcr）。目前，主要发现有四种受体：FFAR1 ~ FFAR4。不同碳链长度的游离脂肪酸（FFAs）对FFAR的反应不同。短链脂肪酸（C2-C6）特异性结合FFAR2和FFAR3，而中链脂肪酸（C6-C12）和长链脂肪酸（C13-C21）同时靶向FFAR1和FFAR4。FFARs被认为是治疗常见代谢性疾病如T2M、心血管疾病和炎症性肠病的潜在靶点。非酒精性脂肪性肝病是一种常见的代谢性疾病，常伴有各种代谢性疾病和心血管疾病。FFARs在体内的表达和调节可能与非酒精性脂肪肝的发生有关。本文介绍了脂肪酸的来源、合成和代谢途径，全面综述了FFARs信号转导及其生理功能的研究、FFARs与NAFLD之间的调控以及基于FFARs治疗NAFLD的前景。

{"title":"Bidirectional regulation of free fatty acid receptors and non-alcoholic fatty liver disease","authors":"Yiyu Lin , Yanglong Liu , Jianshen Liu , Jianxing Wu , Kunhua Wei , Jiao Guo , Zhengquan Su","doi":"10.1016/j.jnutbio.2025.110180","DOIUrl":"10.1016/j.jnutbio.2025.110180","url":null,"abstract":"<div><div>Free fatty acid receptor action is primarily in the area of energy modulation and maintenance of normal metabolism in the body. They have been identified and attributed to specific G protein-coupled receptors (GPCRs). Currently, the main findings include four receptors: FFAR1 to FFAR4. Free fatty acids (FFAs) with different carbon chain lengths respond to different FFAR. Short-chain fatty acids (C2-C6) bind specifically to FFAR2 and FFAR3, whereas medium-chain fatty acids (C6-C12) and long-chain fatty acids (C13-C21) target both FFAR1 and FFAR4. FFARs have been considered as potential target for the treatment of common metabolic diseases such as T2M, cardiovascular diseases and inflammatory bowel diseases. Nonalcoholic fatty liver disease is a common metabolic disorder and is often accompanied by various metabolic and cardiovascular diseases. The expression and modulation of FFARs in the body may be related to the development of nonalcoholic fatty liver disease. This article introduces the source, synthesis and metabolic pathways of fatty acids, and comprehensively summarizes the research on FFARs signal transduction and its physiological functions, the regulation between FFARs and NAFLD, and the prospect of FFARs-based treatment of NAFLD.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110180"},"PeriodicalIF":4.9,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505138","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}

引用次数: 0

Copper-induced duodenal injury: Unveiling the dual role of cuproptosis and ferroptosis via the FDX1/GPX4 axis 铜诱导的十二指肠损伤：通过FDX1/GPX4轴揭示铜下垂和铁下垂的双重作用

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-10 DOI: 10.1016/j.jnutbio.2025.110181

Tao Zhang , Xueyan Dai , Huating Wang , Yang Hu , Xiaona Gao , Xueting Shu , Huabin Cao , Guoliang Hu , Chenghong Xing , Fan Yang

Copper (Cu) is an essential trace element for humans but also a common environmental pollutant. Excessive intake can lead to poisoning, yet the mechanisms by which it causes duodenal injury remain unclear. To investigate the involvement of cuproptosis and ferroptosis in this process, we conducted an experiment using 72 one-day-old Peking ducks, randomly assigned to four groups according to dietary Cu levels: control, 100 mg/kg Cu, 200 mg/kg Cu, and 400 mg/kg Cu. Our findings demonstrate that excessive Cu exposure markedly reduced body weight, caused pathological damage to the duodenum, and triggered oxidative stress. Mechanistically, Cu accumulation in tissues suppressed the expression of ATP7A, PDHB, and FDX1, while upregulating DLAT, Lip-DLAT and HSP70, thereby promoting cuproptosis. Subsequently, cuproptosis acts through the FDX1/GPX4 axis to elevate the expression of TfR1 and increase intracellular iron/ferrous ion levels, while reducing the expression of GPX4, SLC7A11, Cyt C, ISCU, FTH-1, and NAF1. These collective alterations ultimately induce ferroptosis. These changes exhibit a dose-dependent relationship with Cu. In summary, our study suggests that excessive Cu disrupts copper homeostasis, initiates cuproptosis, and perturbs iron metabolism through FDX1- and GPX4-mediated regulation, thereby triggering ferroptosis. These results provide new mechanistic insights into Cu-induced cytotoxicity.

铜是人体必需的微量元素，也是一种常见的环境污染物。过量摄入可导致中毒，但其引起十二指肠损伤的机制尚不清楚。为了研究铜沉和铁沉在这一过程中的作用，本试验选用1日龄北京鸭72只，根据饲粮铜水平随机分为对照组、100 mg/kg Cu组、200 mg/kg Cu组和400 mg/kg Cu组。我们的研究结果表明，过量的铜暴露显着降低体重，引起十二指肠病理损伤，并引发氧化应激。机制上，Cu在组织中的积累抑制了ATP7A、PDHB和FDX1的表达，同时上调了DLAT、Lip-DLAT和HSP70，从而促进了铜增生。随后，铜突起通过FDX1/GPX4轴提高TfR1的表达，增加细胞内铁/亚铁离子水平，同时降低GPX4、SLC7A11、Cyt C、ISCU、FTH-1和NAF1的表达。这些集体改变最终导致铁下垂。这些变化与Cu呈剂量依赖关系。综上所述，我们的研究表明，过量的铜会破坏铜体内平衡，引发铜下沉，并通过FDX1-和gpx4介导的调节干扰铁代谢，从而引发铁下沉。这些结果为cu诱导的细胞毒性提供了新的机制见解。

{"title":"Copper-induced duodenal injury: Unveiling the dual role of cuproptosis and ferroptosis via the FDX1/GPX4 axis","authors":"Tao Zhang , Xueyan Dai , Huating Wang , Yang Hu , Xiaona Gao , Xueting Shu , Huabin Cao , Guoliang Hu , Chenghong Xing , Fan Yang","doi":"10.1016/j.jnutbio.2025.110181","DOIUrl":"10.1016/j.jnutbio.2025.110181","url":null,"abstract":"<div><div>Copper (Cu) is an essential trace element for humans but also a common environmental pollutant. Excessive intake can lead to poisoning, yet the mechanisms by which it causes duodenal injury remain unclear. To investigate the involvement of cuproptosis and ferroptosis in this process, we conducted an experiment using 72 one-day-old Peking ducks, randomly assigned to four groups according to dietary Cu levels: control, 100 mg/kg Cu, 200 mg/kg Cu, and 400 mg/kg Cu. Our findings demonstrate that excessive Cu exposure markedly reduced body weight, caused pathological damage to the duodenum, and triggered oxidative stress. Mechanistically, Cu accumulation in tissues suppressed the expression of ATP7A, PDHB, and FDX1, while upregulating DLAT, Lip-DLAT and HSP70, thereby promoting cuproptosis. Subsequently, cuproptosis acts through the FDX1/GPX4 axis to elevate the expression of TfR1 and increase intracellular iron/ferrous ion levels, while reducing the expression of GPX4, SLC7A11, Cyt C, ISCU, FTH-1, and NAF1. These collective alterations ultimately induce ferroptosis. These changes exhibit a dose-dependent relationship with Cu. In summary, our study suggests that excessive Cu disrupts copper homeostasis, initiates cuproptosis, and perturbs iron metabolism through FDX1- and GPX4-mediated regulation, thereby triggering ferroptosis. These results provide new mechanistic insights into Cu-induced cytotoxicity.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110181"},"PeriodicalIF":4.9,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505156","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}

引用次数: 0

L-theanine mediates Hsf1 protection of intestinal mucosal barrier through Bifidobacterium to alleviate heat stress l -茶氨酸通过双歧杆菌介导Hsf1对肠黏膜屏障的保护，缓解热应激。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-07 DOI: 10.1016/j.jnutbio.2025.110177

Huihua Liang , Yue Yang , Kai Yao , Ling Lin , Bin Wang , Sha Liu , Zhihua Gong , Wenjun Xiao

Heat stress compromises the intestinal mucosal barrier, whereas bifidobacteria preserve its structural integrity. L-theanine (LTA) elevates intestinal Bifidobacterium abundance in heat-stressed mice, thereby alleviating barrier damage. This protection may occur through heat shock factor 1 (Hsf1) regulation, though the precise mechanism requires further elucidation. We investigated the mechanism for the protective effect of L-theanine against heat stress: the LTA protects the intestinal mucosal barrier to alleviate heat stress through Hsf1 and is mediated by Bifidobacterium for Hsf1 regulation. These investigations employed LTA interventions in heat-stressed MODE-K cells, Hsf1-knockout mice, pseudo-germ-free mice, and LTA-Bifidobacterium longum (BL) co-culture experiments. In heat-stressed MODE-K cells, LTA intervention significantly increased cell viability, improved mucosal barrier function, and inhibited Hsf1 and its target proteins Hsp70 and Hsph1. These effects were no longer observed in the Hsf1-inhibited cells but were enhanced in the Hsf1-overexpressing cells. Consistently, LTA failed to protect the intestinal mucosal barrier in heat-stressed Hsf1-knockout mice. In pseudo-germ-free mice and co-culture experiments, BL improved intestinal morphology, protected mucosal barrier function, and suppressed Hsf1 and its target proteins. The effects of L-theanine and BL were superior to those of BL alone. These findings indicate that L-theanine protects the intestinal mucosal barrier in a manner dependent on Bifidobacterium and the Hsf1 signaling pathway.

热应激损害肠粘膜屏障，而双歧杆菌保持其结构完整性。l -茶氨酸（LTA）提高热应激小鼠肠道双歧杆菌的丰度，从而减轻屏障损伤。这种保护可能是通过热休克因子1 （Hsf1）的调节发生的，尽管确切的机制需要进一步阐明。我们研究了l -茶氨酸对热应激的保护作用机制：LTA通过Hsf1保护肠黏膜屏障减轻热应激，并通过双歧杆菌介导Hsf1调控。这些研究采用LTA干预热应激MODE-K细胞、hsf1敲除小鼠、伪无菌小鼠和LTA-长双歧杆菌（BL）共培养实验。在热应激MODE-K细胞中，LTA干预可显著提高细胞活力，改善粘膜屏障功能，抑制Hsf1及其靶蛋白Hsp70和Hsph1。这些影响在hsf1抑制细胞中不再观察到，但在hsf1过表达细胞中增强。与此一致的是，LTA在热应激hsf1敲除小鼠中未能保护肠黏膜屏障。在伪无菌小鼠和共培养实验中，BL改善了肠道形态，保护了粘膜屏障功能，抑制了Hsf1及其靶蛋白。l -茶氨酸和BL的作用优于单独使用BL。这些发现表明，l -茶氨酸以依赖双歧杆菌和Hsf1信号通路的方式保护肠黏膜屏障。

{"title":"L-theanine mediates Hsf1 protection of intestinal mucosal barrier through Bifidobacterium to alleviate heat stress","authors":"Huihua Liang , Yue Yang , Kai Yao , Ling Lin , Bin Wang , Sha Liu , Zhihua Gong , Wenjun Xiao","doi":"10.1016/j.jnutbio.2025.110177","DOIUrl":"10.1016/j.jnutbio.2025.110177","url":null,"abstract":"<div><div>Heat stress compromises the intestinal mucosal barrier, whereas bifidobacteria preserve its structural integrity. L-theanine (LTA) elevates intestinal <em>Bifidobacterium</em> abundance in heat-stressed mice, thereby alleviating barrier damage. This protection may occur through heat shock factor 1 (Hsf1) regulation, though the precise mechanism requires further elucidation. We investigated the mechanism for the protective effect of L-theanine against heat stress: the LTA protects the intestinal mucosal barrier to alleviate heat stress through Hsf1 and is mediated by <em>Bifidobacterium</em> for Hsf1 regulation. These investigations employed LTA interventions in heat-stressed MODE-K cells, <em>Hsf1</em>-knockout mice, pseudo-germ-free mice, and LTA-<em>Bifidobacterium longum</em> (BL) co-culture experiments. In heat-stressed MODE-K cells, LTA intervention significantly increased cell viability, improved mucosal barrier function, and inhibited Hsf1 and its target proteins Hsp70 and Hsph1. These effects were no longer observed in the Hsf1-inhibited cells but were enhanced in the Hsf1-overexpressing cells. Consistently, LTA failed to protect the intestinal mucosal barrier in heat-stressed <em>Hsf1</em>-knockout mice. In pseudo-germ-free mice and co-culture experiments, BL improved intestinal morphology, protected mucosal barrier function, and suppressed Hsf1 and its target proteins. The effects of L-theanine and BL were superior to those of BL alone. These findings indicate that L-theanine protects the intestinal mucosal barrier in a manner dependent on <em>Bifidobacterium</em> and the Hsf1 signaling pathway.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110177"},"PeriodicalIF":4.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482522","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}

引用次数: 0

P-coumaric-acid ameliorates acute kidney injury induced by ischemia-reperfusion injury via suppressing ferroptosis 对香豆酸通过抑制铁下垂改善缺血再灌注急性肾损伤。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-07 DOI: 10.1016/j.jnutbio.2025.110175

Yuhang Gong , Jiang Zhu , Zijing Yuan , Jianheng Chen , Jie Song

AKI resulting from IRI has hindered the development of therapeutic drugs due to unclear pathogenesis. Natural herbal monomers, grounded in the concept of food and medicine sharing the same origin, may provide a novel direction for the development of AKI treatments. p-CA, which is abundantly found in vegetables, fruits, and grains, exhibits anti-apoptotic and antioxidant properties, mechanisms that are closely associated with the pathological processes of AKI. Therefore, p-CA could be developed as an effective therapeutic agent for the treatment of AKI. This study aims to elucidate the molecular mechanisms through which p-CA mitigates renal injury in AKI. Kidney injury was evaluated using HE and Masson staining. The expression of iron death-related proteins was assessed using ELISA, qPCR, iron assay, IF, and WB. p-CA inhibits renal damage induced by ischemia-reperfusion injury, regulates iron ion homeostasis in the kidneys, and concurrently suppresses the pathological process of ferroptosis. Additionally, p-CA improves renal injury induced by IRI in vivo and significantly inhibits ferroptosis. Furthermore, p-CA demonstrates notable protective effects against cell damage induced by H/R and Erastin in vitro. Mechanistically, this study reveals that p-CA significantly upregulates the expression of ferroptosis-related proteins, including SLC7A11 and GPX4, ultimately leading to effective alleviation of AKI. p-CA demonstrates significant efficacy in ameliorating kidney injury and inhibiting ferroptosis. The findings from this study are expected to provide experimental evidence for the development of novel therapeutics for AKI.

背景：IRI所致AKI的发病机制尚不明确，阻碍了治疗药物的发展。基于食药同源理念的天然草药单体可能为AKI治疗提供新的发展方向。p-CA大量存在于蔬菜、水果和谷物中，具有抗凋亡和抗氧化的特性，其机制与AKI的病理过程密切相关。因此，p-CA可作为治疗AKI的有效药物。假设/目的：本研究旨在阐明p-CA减轻AKI肾损伤的分子机制。方法:。采用HE和Masson染色评价肾损伤。采用ELISA、qPCR、铁含量测定、IF和WB检测铁死亡相关蛋白的表达。结果：p-CA可抑制缺血再灌注损伤所致肾损害，调节肾内铁离子稳态，同时抑制铁下垂的病理过程。此外，p-CA在体内改善IRI引起的肾损伤，显著抑制铁下垂。此外，p-CA对H/R和Erastin诱导的细胞损伤具有显著的保护作用。在机制上，本研究揭示了p-CA显著上调凋亡相关蛋白SLC7A11和GPX4的表达，最终导致AKI的有效缓解。结论：p-CA具有明显的改善肾损伤和抑制铁下垂的作用。本研究结果有望为AKI新疗法的开发提供实验证据。

{"title":"P-coumaric-acid ameliorates acute kidney injury induced by ischemia-reperfusion injury via suppressing ferroptosis","authors":"Yuhang Gong , Jiang Zhu , Zijing Yuan , Jianheng Chen , Jie Song","doi":"10.1016/j.jnutbio.2025.110175","DOIUrl":"10.1016/j.jnutbio.2025.110175","url":null,"abstract":"<div><div>AKI resulting from IRI has hindered the development of therapeutic drugs due to unclear pathogenesis. Natural herbal monomers, grounded in the concept of food and medicine sharing the same origin, may provide a novel direction for the development of AKI treatments. p-CA, which is abundantly found in vegetables, fruits, and grains, exhibits anti-apoptotic and antioxidant properties, mechanisms that are closely associated with the pathological processes of AKI. Therefore, p-CA could be developed as an effective therapeutic agent for the treatment of AKI. This study aims to elucidate the molecular mechanisms through which p-CA mitigates renal injury in AKI. Kidney injury was evaluated using HE and Masson staining. The expression of iron death-related proteins was assessed using ELISA, qPCR, iron assay, IF, and WB. p-CA inhibits renal damage induced by ischemia-reperfusion injury, regulates iron ion homeostasis in the kidneys, and concurrently suppresses the pathological process of ferroptosis. Additionally, p-CA improves renal injury induced by IRI <em>in vivo</em> and significantly inhibits ferroptosis. Furthermore, p-CA demonstrates notable protective effects against cell damage induced by H/R and Erastin in vitro. Mechanistically, this study reveals that p-CA significantly upregulates the expression of ferroptosis-related proteins, including SLC7A11 and GPX4, ultimately leading to effective alleviation of AKI. p-CA demonstrates significant efficacy in ameliorating kidney injury and inhibiting ferroptosis. The findings from this study are expected to provide experimental evidence for the development of novel therapeutics for AKI.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110175"},"PeriodicalIF":4.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482571","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}

引用次数: 0

Molecular hydrogen mitigates acetaminophen-induced liver injury and enhances the effects of N-acetylcysteine in diabetic mice 分子氢减轻对乙酰氨基酚所致的糖尿病小鼠肝损伤，增强n-乙酰半胱氨酸的作用。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-07 DOI: 10.1016/j.jnutbio.2025.110176

Naomi Kamimura , Katsuya Iuchi , Tsutomu Igarashi , Ikuroh Ohsawa , Chikako Nito , Jitsuo Usuda , Shigeo Ohta

Acetaminophen (APAP) overdose induces severe liver injury, especially in diabetic patients. N-acetylcysteine (NAC) is commonly used as an approved antidote for APAP toxicity; however, its narrow therapeutic window limits its clinical utility. This study investigated the protective effects of molecular hydrogen (H₂) against APAP-induced hepatotoxicity in diabetic mice. Diabetic db/db mice were provided with hydrogen-dissolved water (H₂-water) for two weeks prior to APAP administration. Consumption of H₂-water significantly attenuated APAP-induced liver injury, as evidenced by improved histological findings and decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Using transgenic mice expressing redox-sensitive green fluorescent protein, H₂ was shown to reduce both cytosolic and mitochondrial oxidative stress caused by APAP overdose. We observed that H₂ modulated c-Jun N-terminal kinase (JNK) activation, inhibited mitochondrial translocation of Bax, and suppressed the release of mitochondrial endonucleases. Additionally, H₂ enhanced the expression of the hepatoprotective hormone fibroblast growth factor 21 (FGF21). These findings suggest that H₂ protects against APAP-induced liver injury in diabetic mice by attenuating oxidative stress and upregulating FGF21 expression. Although NAC acts as an antioxidant, H₂ was more effective in reducing mitochondrial oxidative stress. Importantly, co-treatment with H₂ and NAC provided greater protection against APAP-induced hepatotoxicity than NAC alone. This synergistic effect may result from differences in the mechanisms by which NAC and H₂ influence FGF21 expression and mitochondrial oxidative stress. The combination of H₂ and NAC may offer an improved therapeutic strategy for treating APAP-induced liver injury in diabetic patients.

对乙酰氨基酚（APAP）过量可引起严重的肝损伤，尤其是糖尿病患者。n -乙酰半胱氨酸（NAC）通常被用作APAP毒性的批准解毒剂；然而，其狭窄的治疗窗口限制了其临床应用。本研究探讨了分子氢（H₂）对apap诱导的糖尿病小鼠肝毒性的保护作用。糖尿病db/db小鼠在APAP给药前2周给予氢溶解水（H₂-water）。通过改善组织学结果和降低血浆丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平可以证明，H₂水的消耗显著减轻了apap诱导的肝损伤。在表达氧化还原敏感绿色荧光蛋白的转基因小鼠中，H₂被证明可以减少APAP过量引起的细胞质和线粒体氧化应激。我们观察到H₂调节c-Jun n -末端激酶（JNK）的激活，抑制线粒体Bax的易位，抑制线粒体内切酶的释放。此外，H₂增加了肝保护激素成纤维细胞生长因子21 （FGF21）的表达。这些发现表明，H₂通过减轻氧化应激和上调FGF21的表达来保护apap诱导的糖尿病小鼠肝损伤。虽然NAC作为抗氧化剂，但H₂在减少线粒体氧化应激方面更有效。重要的是，与NAC单独处理相比，H₂和NAC共同处理对apap诱导的肝毒性具有更大的保护作用。这种协同效应可能源于NAC和H₂影响FGF21表达和线粒体氧化应激的不同机制。H₂与NAC联合使用可能为治疗糖尿病患者apap诱导的肝损伤提供一种改进的治疗策略。

{"title":"Molecular hydrogen mitigates acetaminophen-induced liver injury and enhances the effects of N-acetylcysteine in diabetic mice","authors":"Naomi Kamimura , Katsuya Iuchi , Tsutomu Igarashi , Ikuroh Ohsawa , Chikako Nito , Jitsuo Usuda , Shigeo Ohta","doi":"10.1016/j.jnutbio.2025.110176","DOIUrl":"10.1016/j.jnutbio.2025.110176","url":null,"abstract":"<div><div>Acetaminophen (APAP) overdose induces severe liver injury, especially in diabetic patients. <em>N</em>-acetylcysteine (NAC) is commonly used as an approved antidote for APAP toxicity; however, its narrow therapeutic window limits its clinical utility. This study investigated the protective effects of molecular hydrogen (H₂) against APAP-induced hepatotoxicity in diabetic mice. Diabetic <em>db/db</em> mice were provided with hydrogen-dissolved water (H₂-water) for two weeks prior to APAP administration. Consumption of H₂-water significantly attenuated APAP-induced liver injury, as evidenced by improved histological findings and decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Using transgenic mice expressing redox-sensitive green fluorescent protein, H₂ was shown to reduce both cytosolic and mitochondrial oxidative stress caused by APAP overdose. We observed that H₂ modulated c-Jun N-terminal kinase (JNK) activation, inhibited mitochondrial translocation of Bax, and suppressed the release of mitochondrial endonucleases. Additionally, H₂ enhanced the expression of the hepatoprotective hormone fibroblast growth factor 21 (FGF21). These findings suggest that H₂ protects against APAP-induced liver injury in diabetic mice by attenuating oxidative stress and upregulating FGF21 expression. Although NAC acts as an antioxidant, H₂ was more effective in reducing mitochondrial oxidative stress. Importantly, co-treatment with H₂ and NAC provided greater protection against APAP-induced hepatotoxicity than NAC alone. This synergistic effect may result from differences in the mechanisms by which NAC and H₂ influence FGF21 expression and mitochondrial oxidative stress. The combination of H₂ and NAC may offer an improved therapeutic strategy for treating APAP-induced liver injury in diabetic patients.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"149 ","pages":"Article 110176"},"PeriodicalIF":4.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482507","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}

引用次数: 0

High-fat diet mediates the formation of nonalcoholic fatty liver by modulating the AhR/miR-132/SIRT1 axis 高脂肪饮食通过调节AhR/miR-132/SIRT1轴介导非酒精性脂肪肝的形成。

IF 4.9 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2025-11-05 DOI: 10.1016/j.jnutbio.2025.110174

Qing Tao , Jing Xie , Yuanzhi Zhou , Yongkang Wu , Hongdeng Xia , Jingjing Wang , Chunwei Zhang , Chengyan Wei , Yong Jin

Nonalcoholic fatty liver disease (NAFLD) is a global public health problem affecting tens of millions of people worldwide. High-fat diet (HFD) has been reported to be associated with liver steatosis. However, the underlying mechanism remains unclear. The aim of this study was to explore the potential mechanism of HFD in hepatic steatosis. To investigate the potential induction of nonalcoholic fatty liver disease (NAFLD) by a high-fat diet (HFD), this study employed both in vitro free fatty acid (FFA) and in vivo HFD-induced NAFLD models. Serum samples from NAFLD patients were analyzed using ELISA and RT-qPCR to assess the expression of relevant indicators. In the in vitro experiments, cells were treated with 1 mM FFA for 24 hours, while in the in vivo experiments, mice were fed an HFD for 9 weeks. Lipid deposition in cells and liver tissues was examined through hematoxylin-eosin (HE) staining and Oil Red O staining. Furthermore, Western blotting, immunofluorescence, chromatin immunoprecipitation, immunohistochemistry, and RT-qPCR were utilized to systematically investigate the regulatory mechanisms underlying cellular and hepatic lipid deposition. The serum expression of AhR and miR-132 was increased and SIRT1 expression was decreased in NAFLD patients. In the high-fat-induced cell/mouse model of NAFLD, AhR and miR-132 expressions were significantly upregulated and negatively correlated with SIRT1 levels. Mechanistically, bioinformatics analysis and chromatin immunoprecipitation experiments confirmed that AhR could bind the miR-132 promoter to transcriptionally activate miR-132. miR-132 inhibitor transfection experiments confirmed that the downregulation of SIRT1 was dependent on miR-132 function. Our results suggest that HFD promotes hepatic lipid deposition through the AhR/miR-132/SIRT1 pathway and accelerates the development of NAFLD.

背景和目的：非酒精性脂肪性肝病（NAFLD）是影响全球数千万人的全球性公共卫生问题。据报道，高脂肪饮食（HFD）与肝脏脂肪变性有关。然而，其潜在机制尚不清楚。本研究的目的是探讨HFD在肝脂肪变性中的潜在机制。方法：为了研究高脂肪饮食（HFD）对非酒精性脂肪性肝病（NAFLD）的潜在诱导作用，本研究采用体外游离脂肪酸（FFA）和体内高脂肪饮食诱导的NAFLD模型。采用ELISA和RT-qPCR检测NAFLD患者血清中相关指标的表达情况。在体外实验中，细胞用1 mM FFA处理24小时，在体内实验中，小鼠用HFD处理9周。采用苏木精-伊红（HE）染色和油红O染色检测细胞和肝组织的脂质沉积。此外，利用Western blotting、免疫荧光、染色质免疫沉淀、免疫组织化学和RT-qPCR系统地研究了细胞和肝脏脂质沉积的调节机制。结果：NAFLD患者血清AhR、miR-132表达升高，SIRT1表达降低。在高脂肪诱导的NAFLD细胞/小鼠模型中，AhR和miR-132的表达显著上调，并与SIRT1水平呈负相关。机制上，生物信息学分析和染色质免疫沉淀实验证实AhR可以结合miR-132启动子转录激活miR-132。miR-132抑制剂转染实验证实SIRT1的下调依赖于miR-132的功能。结论：我们的研究结果表明，HFD通过AhR/miR-132/SIRT1途径促进肝脏脂质沉积，加速NAFLD的发展。

{"title":"High-fat diet mediates the formation of nonalcoholic fatty liver by modulating the AhR/miR-132/SIRT1 axis","authors":"Qing Tao , Jing Xie , Yuanzhi Zhou , Yongkang Wu , Hongdeng Xia , Jingjing Wang , Chunwei Zhang , Chengyan Wei , Yong Jin","doi":"10.1016/j.jnutbio.2025.110174","DOIUrl":"10.1016/j.jnutbio.2025.110174","url":null,"abstract":"<div><div>Nonalcoholic fatty liver disease (NAFLD) is a global public health problem affecting tens of millions of people worldwide. High-fat diet (HFD) has been reported to be associated with liver steatosis. However, the underlying mechanism remains unclear. The aim of this study was to explore the potential mechanism of HFD in hepatic steatosis. To investigate the potential induction of nonalcoholic fatty liver disease (NAFLD) by a high-fat diet (HFD), this study employed both <em>in vitro</em> free fatty acid (FFA) and <em>in vivo</em> HFD-induced NAFLD models. Serum samples from NAFLD patients were analyzed using ELISA and RT-qPCR to assess the expression of relevant indicators. In the <em>in vitro</em> experiments, cells were treated with 1 mM FFA for 24 hours, while <em>in the in vivo</em> experiments, mice were fed an HFD for 9 weeks. Lipid deposition in cells and liver tissues was examined through hematoxylin-eosin (HE) staining and Oil Red O staining. Furthermore, Western blotting, immunofluorescence, chromatin immunoprecipitation, immunohistochemistry, and RT-qPCR were utilized to systematically investigate the regulatory mechanisms underlying cellular and hepatic lipid deposition. The serum expression of AhR and miR-132 was increased and SIRT1 expression was decreased in NAFLD patients. In the high-fat-induced cell/mouse model of NAFLD, AhR and miR-132 expressions were significantly upregulated and negatively correlated with SIRT1 levels. Mechanistically, bioinformatics analysis and chromatin immunoprecipitation experiments confirmed that AhR could bind the miR-132 promoter to transcriptionally activate miR-132. miR-132 inhibitor transfection experiments confirmed that the downregulation of SIRT1 was dependent on miR-132 function. Our results suggest that HFD promotes hepatic lipid deposition through the AhR/miR-132/SIRT1 pathway and accelerates the development of NAFLD.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"148 ","pages":"Article 110174"},"PeriodicalIF":4.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471329","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}

引用次数: 0