Journal of Nutritional Biochemistry最新文献_第7页

PBMC transcriptome reveals an early metabolic risk profile in young rats with metabolically obese, normal-weight phenotype 白细胞介素转录组揭示了代谢性肥胖正常体重表型幼鼠的早期代谢风险特征。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-26 DOI: 10.1016/j.jnutbio.2024.109790

Carmen García-Ruano , Andrea Costa , Andreu Palou , Paula Oliver

Metabolically obese, normal-weight (MONW) phenotype is characterized by visceral adiposity and obesity-related complications despite the absence of excess body weight. Early identification of this phenotype is crucial to establish preventive strategies. We aim to validate the utility of peripheral blood mononuclear cells (PBMC) transcriptome to detect metabolic risk related to the MONW phenotype at early life stages (young adulthood). Male Wistar rats were pair-fed either standard (NW group) or a high-fat diet (MONW group) after weaning, until 3.5 months. Global gene expression was examined by microarray in PBMC, and specific genes of interest by RT-qPCR in PBMC and liver. Results were validated in adult 6-month-old MONW rats. Young MONW animals had similar weight to controls (NW group) but greater adiposity, including liver fat content, and insulin resistance signs. PBMC transcriptome distinguished clearly MONW from NW rats. Neurological pathways were affected in line with impaired cognition in these animals. Most top-regulated genes were related to inflammation, including the top-up and down-regulated genes, Hpgds and Slfn4. Expression of fatty liver-related genes like Mkrn1 and Nampt was also affected in PBMC of the young MONW group mirroring liver alteration. Slfn4 and Mkrn1 appeared as especially relevant biomarkers with altered expression also in PBMC of adult 6-month-old MONW rats. In conclusion, PBMC transcriptomic analysis emerges as a tool for identifying early biomarkers of obesity-related metabolic risk in young and apparently healthy (lean) subjects, pointing towards increased inflammation, liver fat deposition, and cognitive alterations.

代谢性肥胖、正常体重（MONW）表型的特点是内脏脂肪过多，尽管体重没有超标，但会出现与肥胖相关的并发症。早期识别这种表型对于制定预防策略至关重要。我们的目的是验证外周血单核细胞（PBMC）转录组在早期生命阶段（青年期）检测与 MONW 表型相关的代谢风险的实用性。雄性 Wistar 大鼠断奶后接受标准（NW 组）或高脂饮食（MONW 组）配对喂养，直至 3 个半月。通过微阵列检测白细胞介质中的全基因表达，通过 RT-qPCR 检测白细胞介质和肝脏中的特定相关基因。研究结果在 6 个月大的成年 MONW 大鼠身上得到了验证。年幼的 MONW 大鼠体重与对照组相似，但脂肪含量（包括肝脏脂肪含量）和胰岛素抵抗症状却更高。PBMC转录组明显区分了MONW和NW动物。这些动物的神经通路受到影响，认知能力受损。大多数上调基因与炎症有关，包括上调和下调基因Hpgds和Slfn4。与脂肪肝有关的基因如Mkrn1和Nampt的表达在年轻的MONW组的白细胞介体中也受到影响，这反映了肝脏的改变。在 6 个月大的成年 MONW 大鼠的 PBMC 中，Slfn4 和 Mkrn1 似乎是特别相关的生物标志物，其表达也发生了改变。总之，PBMC 转录组分析可作为一种工具，用于识别年轻、表面健康（瘦）的受试者中与肥胖相关的代谢风险的早期生物标志物，并指出炎症、肝脏脂肪沉积和认知改变的增加。

{"title":"PBMC transcriptome reveals an early metabolic risk profile in young rats with metabolically obese, normal-weight phenotype","authors":"Carmen García-Ruano , Andrea Costa , Andreu Palou , Paula Oliver","doi":"10.1016/j.jnutbio.2024.109790","DOIUrl":"10.1016/j.jnutbio.2024.109790","url":null,"abstract":"<div><div>Metabolically obese, normal-weight (MONW) phenotype is characterized by visceral adiposity and obesity-related complications despite the absence of excess body weight. Early identification of this phenotype is crucial to establish preventive strategies. We aim to validate the utility of peripheral blood mononuclear cells (PBMC) transcriptome to detect metabolic risk related to the MONW phenotype at early life stages (young adulthood). Male Wistar rats were pair-fed either standard (NW group) or a high-fat diet (MONW group) after weaning, until 3.5 months. Global gene expression was examined by microarray in PBMC, and specific genes of interest by RT-qPCR in PBMC and liver. Results were validated in adult 6-month-old MONW rats. Young MONW animals had similar weight to controls (NW group) but greater adiposity, including liver fat content, and insulin resistance signs. PBMC transcriptome distinguished clearly MONW from NW rats. Neurological pathways were affected in line with impaired cognition in these animals. Most top-regulated genes were related to inflammation, including the top-up and down-regulated genes, <em>Hpgds</em> and <em>Slfn4</em>. Expression of fatty liver-related genes like <em>Mkrn1</em> and <em>Nampt</em> was also affected in PBMC of the young MONW group mirroring liver alteration. <em>Slfn4</em> and <em>Mkrn1</em> appeared as especially relevant biomarkers with altered expression also in PBMC of adult 6-month-old MONW rats. In conclusion, PBMC transcriptomic analysis emerges as a tool for identifying early biomarkers of obesity-related metabolic risk in young and apparently healthy (lean) subjects, pointing towards increased inflammation, liver fat deposition, and cognitive alterations.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"136 ","pages":"Article 109790"},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retinol metabolism signaling participates in microbiota-regulated fat deposition in obese mice 视黄醇代谢信号参与肥胖小鼠体内微生物群调节的脂肪沉积。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-25 DOI: 10.1016/j.jnutbio.2024.109787

Hui Han , Shunfen Zhang , Mengyu Wang , Bao Yi , Yong Zhao , Martine Schroyen , Hongfu Zhang

Obesity is a global pandemic threatening public health, excess fat accumulation and overweight are its characteristics. In this study, the interplay between gut microbiota and retinol metabolism in modulating fat accumulation was verified. We observed gut microbiota depletion reduced the body weight and the ratios of white adipose tissues (WATs) to body weight in high-fat diet (HFD) fed-mice. The kyoto encyclopedia of genes and genomes (KEGG) analysis and protein-protein interaction (PPI) network of RNA-seq results indicated that retinol metabolism signaling may be involved in the microbiota-regulated fat deposition. Furthermore, activated retinol metabolism signaling by all-trans retinoic acid (atRA) supplementation reduced body weight and WAT accumulation in obese mice. 16S rRNA gene sequencing of the ileal microbiota suggested that atRA supplementation increased the microbial diversity and induced the growth of beneficial bacteria including Parabacteroides, Bacteroides, Clostridium_XVIII, Bifidobacterium, Enterococcus, Bacillus, Leuconostoc, and Lactobacillus in obese mice. Spearman correlation showed that the microbiota altered by atRA were associated with body and WAT weights. Together, this study reveals the interaction between the gut microbiota and retinol metabolism signaling in regulating adipose accumulation and obesity. It is expected of this finding to provide new insights to prevent and develop therapeutic measures of obesity-related metabolic syndrome.

肥胖症是威胁公众健康的全球性流行病，脂肪堆积过多和超重是其特征。本研究验证了肠道微生物群与视黄醇代谢之间在调节脂肪积累方面的相互作用。我们观察到，肠道微生物群减少会降低体重（P

{"title":"Retinol metabolism signaling participates in microbiota-regulated fat deposition in obese mice","authors":"Hui Han , Shunfen Zhang , Mengyu Wang , Bao Yi , Yong Zhao , Martine Schroyen , Hongfu Zhang","doi":"10.1016/j.jnutbio.2024.109787","DOIUrl":"10.1016/j.jnutbio.2024.109787","url":null,"abstract":"<div><div>Obesity is a global pandemic threatening public health, excess fat accumulation and overweight are its characteristics. In this study, the interplay between gut microbiota and retinol metabolism in modulating fat accumulation was verified. We observed gut microbiota depletion reduced the body weight and the ratios of white adipose tissues (WATs) to body weight in high-fat diet (HFD) fed-mice. The kyoto encyclopedia of genes and genomes (KEGG) analysis and protein-protein interaction (PPI) network of RNA-seq results indicated that retinol metabolism signaling may be involved in the microbiota-regulated fat deposition. Furthermore, activated retinol metabolism signaling by all-trans retinoic acid (atRA) supplementation reduced body weight and WAT accumulation in obese mice. 16S rRNA gene sequencing of the ileal microbiota suggested that atRA supplementation increased the microbial diversity and induced the growth of beneficial bacteria including <em>Parabacteroides, Bacteroides, Clostridium_XVIII, Bifidobacterium, Enterococcus, Bacillus, Leuconostoc</em>, and <em>Lactobacillus</em> in obese mice. Spearman correlation showed that the microbiota altered by atRA were associated with body and WAT weights. Together, this study reveals the interaction between the gut microbiota and retinol metabolism signaling in regulating adipose accumulation and obesity. It is expected of this finding to provide new insights to prevent and develop therapeutic measures of obesity-related metabolic syndrome.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"136 ","pages":"Article 109787"},"PeriodicalIF":4.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502431","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

Lipidomic profiling of serum and liver tissue reveals hepatoprotective mechanism of taxifolin in rats with CCl4-induced subacute hepatic injury based on LC-MS/MS 基于LC-MS/MS的血清和肝组织脂质组图谱分析揭示了taxifolin对CCl4诱导的亚急性肝损伤大鼠的保肝机制。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-24 DOI: 10.1016/j.jnutbio.2024.109788

Yiming Ni , Xinghua Chen , Yiqun Jia , Long Chen , Mingmei Zhou

Currently, the hepatoprotective activity of taxifolin, a flavonoid isolated from Pseudotsuga taxifolia, has been reported in many animal models. However, whether the protective effect of taxifolin on the liver is related to its effect on lipidomics is unclear. Based on the significant therapeutic effect of taxifolin on CCl₄ induced subacute hepatic injury, we observed the intervention of taxifolin by lipidomics. The results demonstrate that taxifolin can effectively reverse the damage caused by CCl₄, which including hepatocyte vacuolization and necrosis. Lipomic profiling based on liquid chromatography-mass spectrometry showed that taxifolin was able to restore lipidomic changes caused by CCl₄, including the levels of lysophosphatidylserine (LPS), phosphatidylcholine (PC), coenzyme (Co), phosphatidylglyceride (PG), phosphatidylserine (PS), dimethylphosphatidylethanolamine (dMePE), ceramide (Cer), sphingosine (So), triglycerides (TG), and monogalactosyl diacylglycerol (MGDG) in the rat liver, and phosphatidylcarbinol (PMe) and phosphatidylethanolamine (PE), plant sphingosine (phSM), glucose ceramide (CerG1), TG, and diglycerides (DG) in serum. Spearman's correlation analysis showed that CerG1, phSM, PE, and PMe in serum, and Cer, dMePE, PG, PS, So, TG, and MGDG in liver were positively correlated with serum levels of aspartate transaminase, alanine transaminase, and liver index; while TG, DG in serum, and Co, LPS, PC in liver were negatively correlated with the parameters. In total, 43 and 34 lipid molecules were altered by taxifolin treatment in the liver and serum, respectively, mainly including glycerophosphoglycerols, glycerophosphocholines, glycerophosphoethanolamines, and linoleic acids and derivatives. Our findings help to provide novel insights into the mechanism of the hepatoprotective effect of taxifolin from a lipidomics approach.

目前，从红豆杉（Pseudotsuga taxifolia）中分离出的一种黄酮类化合物--紫杉叶黄酮（taxifolin）的保肝活性已在许多动物模型中得到报道。然而，taxifolin 对肝脏的保护作用是否与其对脂质组学的影响有关尚不清楚。基于taxifolin对CCl4诱导的亚急性肝损伤的显著疗效，我们观察了脂质组学对taxifolin的干预作用。结果表明，紫杉叶素能有效逆转 CCl4 引起的损伤，包括肝细胞空泡化和坏死。基于液相色谱-质谱联用技术的脂质组学分析表明，紫杉叶素能恢复CCl4引起的脂质组学变化，包括溶血磷脂酰丝氨酸（LPS）、磷脂酰胆碱（PC）、辅酶（Co）、磷脂酰甘油（PG）、磷脂酰丝氨酸（PS）、二甲基磷脂酰乙酰胆碱（PC）和二甲基磷脂酰乙酰胆碱（PS）的水平、大鼠肝脏中的磷脂酰胆碱（PC）、辅酶（Co）、磷脂酰甘油酯（PG）、磷脂酰丝氨酸（PS）、二甲基磷脂酰乙醇胺（dMePE）、神经酰胺（Cer）、鞘磷脂（So）、甘油三酯（TG）和单半乳糖二酰甘油（MGDG），以及血清中的磷脂酰卡宾醇（PMe）、磷脂酰乙醇胺（PE）、植物鞘磷脂（phSM）、葡萄糖神经酰胺（CerG1）、TG 和二甘油酯（DG）。斯皮尔曼相关分析表明，血清中的 CerG1、phSM、PE 和 PMe，肝脏中的 Cer、dMePE、PG、PS、So、TG 和 MGDG 与血清中的天门冬氨酸转氨酶、丙氨酸转氨酶和肝脏指数呈正相关；而血清中的 TG、DG 和肝脏中的 Co、LPS、PC 与上述参数呈负相关。taxifolin处理分别改变了肝脏和血清中43和34种脂质分子，主要包括甘油磷酸甘油、甘油磷酸胆碱、甘油磷酸乙醇胺、亚油酸及其衍生物。我们的研究结果有助于从脂质组学的角度对紫杉叶素的保肝作用机制提供新的见解。

{"title":"Lipidomic profiling of serum and liver tissue reveals hepatoprotective mechanism of taxifolin in rats with CCl4-induced subacute hepatic injury based on LC-MS/MS","authors":"Yiming Ni , Xinghua Chen , Yiqun Jia , Long Chen , Mingmei Zhou","doi":"10.1016/j.jnutbio.2024.109788","DOIUrl":"10.1016/j.jnutbio.2024.109788","url":null,"abstract":"<div><div>Currently, the hepatoprotective activity of taxifolin, a flavonoid isolated from <em>Pseudotsuga taxifolia</em>, has been reported in many animal models. However, whether the protective effect of taxifolin on the liver is related to its effect on lipidomics is unclear. Based on the significant therapeutic effect of taxifolin on CCl<sub>4</sub> induced subacute hepatic injury, we observed the intervention of taxifolin by lipidomics. The results demonstrate that taxifolin can effectively reverse the damage caused by CCl<sub>4</sub>, which including hepatocyte vacuolization and necrosis. Lipomic profiling based on liquid chromatography-mass spectrometry showed that taxifolin was able to restore lipidomic changes caused by CCl<sub>4</sub>, including the levels of lysophosphatidylserine (LPS), phosphatidylcholine (PC), coenzyme (Co), phosphatidylglyceride (PG), phosphatidylserine (PS), dimethylphosphatidylethanolamine (dMePE), ceramide (Cer), sphingosine (So), triglycerides (TG), and monogalactosyl diacylglycerol (MGDG) in the rat liver, and phosphatidylcarbinol (PMe) and phosphatidylethanolamine (PE), plant sphingosine (phSM), glucose ceramide (CerG1), TG, and diglycerides (DG) in serum. Spearman's correlation analysis showed that CerG1, phSM, PE, and PMe in serum, and Cer, dMePE, PG, PS, So, TG, and MGDG in liver were positively correlated with serum levels of aspartate transaminase, alanine transaminase, and liver index; while TG, DG in serum, and Co, LPS, PC in liver were negatively correlated with the parameters. In total, 43 and 34 lipid molecules were altered by taxifolin treatment in the liver and serum, respectively, mainly including glycerophosphoglycerols, glycerophosphocholines, glycerophosphoethanolamines, and linoleic acids and derivatives. Our findings help to provide novel insights into the mechanism of the hepatoprotective effect of taxifolin from a lipidomics approach.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"136 ","pages":"Article 109788"},"PeriodicalIF":4.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502430","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

Butyrolactone-I from marine fungi alleviates intestinal barrier damage caused by DSS through regulating lactobacillus johnsonii and its metabolites in the intestine of mice 海洋真菌中的丁内酯-I通过调节小鼠肠道中的约翰逊乳杆菌及其代谢产物，减轻了DSS造成的肠道屏障损伤。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-22 DOI: 10.1016/j.jnutbio.2024.109786

Shengwei Chen , Xueting Niu , Yi Zhang , Jiaying Wen , Minglong Bao , Yin Li , Yuan Gao , Xinchen Wang , Xiaoxi Liu , Yanhong Yong , Zhichao Yu , Xingbing Ma , Jong-Bang Eun , Jae-Han Shim , A. M. Abd El-Aty , Xianghong Ju

Butyrolactone-I (BTL-1), a secondary metabolite from the marine fungus Aspergillus terreus, exhibits numerous biological activities. Previous research has indicated that Butyrolactone-I alleviates intestinal epithelial inflammation via the TLR4/NF-κB and MAPK pathways. However, the mechanisms underlying its protection against intestinal barrier damage remain unclear. This study aims to further elucidate these mechanisms. We observed that BTL-1 administration increased the abundance of Lactobacillus johnsonii (LJ) in both in vivo and in vitro experiments, prompting an investigation into the effects of LJ and its metabolites on DSS-induced inflammatory bowel disease (IBD). The results demonstrated that BTL-1 significantly upregulated tight junction (TJ) and adherens junction (AJ) proteins, maintained intestinal barrier integrity, and alleviated DSS-induced IBD in mice. These effects were associated with the proliferation of LJ and its metabolites, such as butyric and propionic acids, and the inhibition of the MAPK signaling pathway in the colon. Interestingly, administering LJ alone produced a protective effect against DSS-induced IBD similar to that observed with BTL-1. Furthermore, butyric acid, a metabolite of LJ, also upregulated TJ/AJ proteins in intestinal epithelial cells through the MAPK signaling pathway. Our findings suggest that BTL-1 regulates intestinal flora, promotes LJ proliferation, protects intestinal barrier integrity, increases the concentrations of butyric and propionic acids, and ultimately inhibits the activation of the MAPK signaling pathway in mice to alleviate IBD. Therefore, BTL-1 could potentially be used as a natural drug to prevent IBD and maintain intestinal flora balance. We explored how butyrolactone-I exerts a preventive effect on IBD through intestinal bacteria (Lactobacillus johnsonii).

丁内酯-I（BTL-1）是海洋真菌赤曲霉的次级代谢产物，具有多种生物活性。以往的研究表明，丁内酯-I 可通过 TLR4/NF-κB 和 MAPK 途径缓解肠上皮炎症。然而，其保护肠道屏障免受损伤的机制仍不清楚。本研究旨在进一步阐明这些机制。我们观察到，在体内和体外实验中，BTL-1 都能增加约翰逊乳杆菌（LJ）的丰度，这促使我们研究 LJ 及其代谢物对 DSS 诱导的炎症性肠病（IBD）的影响。结果表明，BTL-1 能显著上调紧密连接（TJ）和粘连连接（AJ）蛋白，维持肠道屏障的完整性，并缓解 DSS 诱导的小鼠 IBD。这些作用与 LJ 及其代谢物（如丁酸和丙酸）的增殖以及结肠中 MAPK 信号通路的抑制有关。有趣的是，单独服用 LJ 对 DSS 诱导的 IBD 产生的保护作用与 BTL-1 的效果相似。此外，LJ 的代谢产物丁酸也能通过 MAPK 信号通路上调肠上皮细胞中的 TJ/AJ 蛋白。我们的研究结果表明，BTL-1 可调节肠道菌群、促进 LJ 增殖、保护肠道屏障完整性、增加丁酸和丙酸的浓度，并最终抑制小鼠 MAPK 信号通路的激活，从而缓解 IBD。因此，BTL-1 有可能被用作预防 IBD 和维持肠道菌群平衡的天然药物。重要性：我们探讨了丁内酯-I如何通过肠道细菌（约翰逊乳杆菌）对IBD产生预防作用。

{"title":"Butyrolactone-I from marine fungi alleviates intestinal barrier damage caused by DSS through regulating lactobacillus johnsonii and its metabolites in the intestine of mice","authors":"Shengwei Chen , Xueting Niu , Yi Zhang , Jiaying Wen , Minglong Bao , Yin Li , Yuan Gao , Xinchen Wang , Xiaoxi Liu , Yanhong Yong , Zhichao Yu , Xingbing Ma , Jong-Bang Eun , Jae-Han Shim , A. M. Abd El-Aty , Xianghong Ju","doi":"10.1016/j.jnutbio.2024.109786","DOIUrl":"10.1016/j.jnutbio.2024.109786","url":null,"abstract":"<div><div>Butyrolactone-I (BTL-1), a secondary metabolite from the marine fungus <em>Aspergillus terreus</em>, exhibits numerous biological activities. Previous research has indicated that Butyrolactone-I alleviates intestinal epithelial inflammation via the TLR4/NF-κB and MAPK pathways. However, the mechanisms underlying its protection against intestinal barrier damage remain unclear. This study aims to further elucidate these mechanisms. We observed that BTL-1 administration increased the abundance of <em>Lactobacillus johnsonii</em> (<em>LJ</em>) in both <em>in vivo</em> and <em>in vitro</em> experiments, prompting an investigation into the effects of <em>LJ</em> and its metabolites on DSS-induced inflammatory bowel disease (IBD). The results demonstrated that BTL-1 significantly upregulated tight junction (TJ) and adherens junction (AJ) proteins, maintained intestinal barrier integrity, and alleviated DSS-induced IBD in mice. These effects were associated with the proliferation of <em>LJ</em> and its metabolites, such as butyric and propionic acids, and the inhibition of the MAPK signaling pathway in the colon. Interestingly, administering <em>LJ</em> alone produced a protective effect against DSS-induced IBD similar to that observed with BTL-1. Furthermore, butyric acid, a metabolite of <em>LJ</em>, also upregulated TJ/AJ proteins in intestinal epithelial cells through the MAPK signaling pathway. Our findings suggest that BTL-1 regulates intestinal flora, promotes LJ proliferation, protects intestinal barrier integrity, increases the concentrations of butyric and propionic acids, and ultimately inhibits the activation of the MAPK signaling pathway in mice to alleviate IBD. Therefore, BTL-1 could potentially be used as a natural drug to prevent IBD and maintain intestinal flora balance. We explored how butyrolactone-I exerts a preventive effect on IBD through intestinal bacteria (<em>Lactobacillus johnsonii</em>).</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109786"},"PeriodicalIF":4.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502417","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

Impact of reduced hepatic ceramide levels in high-fat diet mice on glucose metabolism 高脂饮食小鼠肝神经酰胺水平降低对葡萄糖代谢的影响。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-19 DOI: 10.1016/j.jnutbio.2024.109785

Monika Imierska , Piotr Zabielski , Kamila Roszczyc-Owsiejczuk , Karolina Pogodzińska , Agnieszka Błachnio-Zabielska

Dysregulation of insulin action in hepatocytes, common in obesity, significantly contributes to insulin resistance, type 2 diabetes, and metabolic syndrome. Previous research highlights ceramides' role in these conditions. This study explores the impact of ceramides by silencing the serine palmitoyltransferase (Sptlc2) gene, crucial for the initial ceramide biosynthesis, using hydrodynamic gene delivery. Male C57BL/6 mice were randomly divided into three groups: one on a low-fat diet (LFD) receiving scrambled shRNA plasmids, another on a high-fat diet (HFD) with scrambled shRNA plasmids, and a third on HFD with a plasmid targeting Sptlc2. Analyses included RT-PCR for gene expression, western blot for protein levels, and UHPLC/MS/MS for lipid profiling. Glucose metabolism was evaluated via oral glucose tolerance tests, homeostatic model assessment of insulin resistance, and glucose-6-phosphate analysis. Results showed that HFD induces insulin resistance by inhibiting insulin signaling and increasing active lipid levels in hepatocytes. Sptlc2 silencing reduced ceramide accumulation, improving insulin signaling and glucose metabolism. Notably, ceramide synthesis inhibition did not significantly affect other lipid levels, highlighting ceramide's critical role in hepatic insulin resistance.

肝细胞中的胰岛素作用失调在肥胖症中很常见，是导致胰岛素抵抗、2 型糖尿病和代谢综合征的重要原因。以往的研究强调了神经酰胺在这些病症中的作用。本研究利用流体动力基因递送技术，通过沉默丝氨酸棕榈酰基转移酶（Sptlc2）基因来探讨神经酰胺的影响，丝氨酸棕榈酰基转移酶对神经酰胺的初始生物合成至关重要。雄性 C57BL/6 小鼠被随机分为三组：一组以低脂饮食（LFD）为主，接受乱码 shRNA 质粒；另一组以高脂饮食（HFD）为主，接受乱码 shRNA 质粒；第三组以高脂饮食为主，接受靶向 Sptlc2 的质粒。分析包括基因表达的 RT-PCR、蛋白质水平的 Western 印迹和脂质分析的 UHPLC/MS/MS。葡萄糖代谢通过口服葡萄糖耐量试验、胰岛素抵抗的稳态模型评估和葡萄糖-6-磷酸分析进行评估。结果表明，高密度脂蛋白膳食通过抑制胰岛素信号传导和增加肝细胞中的活性脂质水平诱导胰岛素抵抗。沉默 Sptlc2 可减少神经酰胺的积累，改善胰岛素信号传导和葡萄糖代谢。值得注意的是，抑制神经酰胺的合成并不会显著影响其他脂质水平，这凸显了神经酰胺在肝脏胰岛素抵抗中的关键作用。

{"title":"Impact of reduced hepatic ceramide levels in high-fat diet mice on glucose metabolism","authors":"Monika Imierska , Piotr Zabielski , Kamila Roszczyc-Owsiejczuk , Karolina Pogodzińska , Agnieszka Błachnio-Zabielska","doi":"10.1016/j.jnutbio.2024.109785","DOIUrl":"10.1016/j.jnutbio.2024.109785","url":null,"abstract":"<div><div>Dysregulation of insulin action in hepatocytes, common in obesity, significantly contributes to insulin resistance, type 2 diabetes, and metabolic syndrome. Previous research highlights ceramides' role in these conditions. This study explores the impact of ceramides by silencing the serine palmitoyltransferase (<em>Sptlc2</em>) gene, crucial for the initial ceramide biosynthesis, using hydrodynamic gene delivery. Male C57BL/6 mice were randomly divided into three groups: one on a low-fat diet (LFD) receiving scrambled shRNA plasmids, another on a high-fat diet (HFD) with scrambled shRNA plasmids, and a third on HFD with a plasmid targeting Sptlc2. Analyses included RT-PCR for gene expression, western blot for protein levels, and UHPLC/MS/MS for lipid profiling. Glucose metabolism was evaluated via oral glucose tolerance tests, homeostatic model assessment of insulin resistance, and glucose-6-phosphate analysis. Results showed that HFD induces insulin resistance by inhibiting insulin signaling and increasing active lipid levels in hepatocytes. <em>Sptlc2</em> silencing reduced ceramide accumulation, improving insulin signaling and glucose metabolism. Notably, ceramide synthesis inhibition did not significantly affect other lipid levels, highlighting ceramide's critical role in hepatic insulin resistance.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109785"},"PeriodicalIF":4.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468093","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

Behavioral changes and transcriptional regulation of mesolimbic dopaminergic genes in a mouse model of binge eating disorder by diet intermittent access 饮食间歇性接触暴饮暴食症小鼠模型的行为变化和间叶多巴胺能基因的转录调控。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-18 DOI: 10.1016/j.jnutbio.2024.109784

Renato Elias Moreira Júnior , Agatha Sondertoft Braga Pedersen , Raquel Mary Ferreira , Guilherme Henrique de Asevedo , Grazielle Laudares Mendes , Karine Ribeiro , Tatiani Uceli Maioli , Ana Maria Caetano de Faria , Ana Lúcia Brunialti-Godard

Binge Eating Disorder (BED) is among the most prevalent eating disorders worldwide. It is characterized by recurrent episodes of excessive consumption of palatable foods in short periods, accompanied by a sense of loss of control and distress around the episode, which tends to worsen over time. The mesolimbic dopaminergic system influences on reinforcement and reward-seeking behaviors is implicated in the disorder's pathogenesis. Animal models that replicate the clinical conditions observed in humans, including the disorder progression, are essential for understanding the underlying physiological mechanisms of BED. This study aimed to evaluate binge eating behavior induced by intermittent High Sugar and Butter (HSB) diet access in mice, their phenotypes, transcriptional regulation of mesolimbic dopaminergic system genes, and behavior. Thus, mice were subdivided into three groups: CHOW (maintenance diet only), HSB-i (maintenance diet with thrice-weekly access to HSB), and HSB (continuous access to HSB). Animals were subjected to marble-burying and light-dark box behavioral tests, and transcriptional regulation was evaluated by RT-qPCR. The results indicated that the HSB-i group established a feeding pattern of significantly more kilocalories on days when HSB was available and reduced intake on non-HSB days similar to human binge eating. Over time, binge episodes intensified, potentially indicating a tolerance effect. Additionally, these animals behave differently towards preferring the HSB diet and exhibited altered transcriptional regulation of the Drd1, Slc6a3, and Lrrk2 genes. Our study provides a mouse model that reflects human BED, showing a progression in binge episodes and mesolimbic dopamine pathway involvement, suggesting targets for future therapeutic interventions.

暴饮暴食症（BED）是全球最普遍的饮食失调症之一。它的特点是反复发作，在短期内摄入过多适口食物，并伴有失控感和围绕发作的痛苦，这种情况往往会随着时间的推移而恶化。中边缘多巴胺能系统对强化和寻求奖赏行为的影响与该疾病的发病机制有关。复制人类临床症状（包括疾病进展）的动物模型对于了解暴食症的潜在生理机制至关重要。本研究旨在评估小鼠间歇性摄入高糖高黄油（HSB）饮食诱发的暴食行为、其表型、间叶多巴胺能系统基因的转录调控以及行为。因此，小鼠被细分为三组：CHOW（仅摄入维持性饮食）、HSB-i（摄入维持性饮食，每周三次摄入 HSB）和 HSB（持续摄入 HSB）。对动物进行埋大理石和光-暗箱行为测试，并通过 RT-qPCR 评估转录调控。结果表明，HSB-i 组建立了一种进食模式，即在有 HSB 的日子里摄入的热量显著增加，而在没有 HSB 的日子里摄入的热量则减少，这与人类的暴饮暴食类似。随着时间的推移，暴食现象会加剧，这可能表明存在耐受效应。此外，这些动物对 HSB 饮食的偏好表现不同，并表现出 Drd1、Slc6a3 和 Lrrk2 基因转录调控的改变。我们的研究提供了一个反映人类暴饮暴食症的小鼠模型，显示了暴饮暴食发作的进展和间叶多巴胺通路的参与，为未来的治疗干预提出了目标。

{"title":"Behavioral changes and transcriptional regulation of mesolimbic dopaminergic genes in a mouse model of binge eating disorder by diet intermittent access","authors":"Renato Elias Moreira Júnior , Agatha Sondertoft Braga Pedersen , Raquel Mary Ferreira , Guilherme Henrique de Asevedo , Grazielle Laudares Mendes , Karine Ribeiro , Tatiani Uceli Maioli , Ana Maria Caetano de Faria , Ana Lúcia Brunialti-Godard","doi":"10.1016/j.jnutbio.2024.109784","DOIUrl":"10.1016/j.jnutbio.2024.109784","url":null,"abstract":"<div><div>Binge Eating Disorder (BED) is among the most prevalent eating disorders worldwide. It is characterized by recurrent episodes of excessive consumption of palatable foods in short periods, accompanied by a sense of loss of control and distress around the episode, which tends to worsen over time. The mesolimbic dopaminergic system influences on reinforcement and reward-seeking behaviors is implicated in the disorder's pathogenesis. Animal models that replicate the clinical conditions observed in humans, including the disorder progression, are essential for understanding the underlying physiological mechanisms of BED. This study aimed to evaluate binge eating behavior induced by intermittent High Sugar and Butter (HSB) diet access in mice, their phenotypes, transcriptional regulation of mesolimbic dopaminergic system genes, and behavior. Thus, mice were subdivided into three groups: CHOW (maintenance diet only), HSB-i (maintenance diet with thrice-weekly access to HSB), and HSB (continuous access to HSB). Animals were subjected to marble-burying and light-dark box behavioral tests, and transcriptional regulation was evaluated by RT-qPCR. The results indicated that the HSB-i group established a feeding pattern of significantly more kilocalories on days when HSB was available and reduced intake on non-HSB days similar to human binge eating. Over time, binge episodes intensified, potentially indicating a tolerance effect. Additionally, these animals behave differently towards preferring the HSB diet and exhibited altered transcriptional regulation of the <em>Drd1, Slc6a3</em>, and <em>Lrrk2</em> genes. Our study provides a mouse model that reflects human BED, showing a progression in binge episodes and mesolimbic dopamine pathway involvement, suggesting targets for future therapeutic interventions.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109784"},"PeriodicalIF":4.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468092","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

Tsg101 knockout in the mammary gland leads to a decrease in small extracellular vesicles in milk from C57BL/6J dams and contributes to leakiness of the gut mucosa and reduced postnatal weight gain in suckling pups 乳腺中的Tsg101基因敲除会导致C57BL/6J母鼠乳汁中的小细胞外囊泡减少，并导致肠道粘膜渗漏和哺乳幼鼠出生后体重增加减少。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-17 DOI: 10.1016/j.jnutbio.2024.109782

Javaria Munir , Mahrou Sadri , Janos Zempleni

Human milk contains 2.2 ± 1.5×10¹¹ small extracellular vesicles (sEVs) per milliliter and human infants consume 1.7×10¹⁴ milk sEVs (sMEVs) daily in 800 mL milk. Infant formula contains trace amounts of sMEVs. To date, eight adverse effects of milk depletion and five beneficial effects of sMEV supplementation have been reported including studies in infants and neonate mice. Formula-fed infants do not realize the benefits of sMEVs. Most of the phenotyping studies reported to date have the limitation that sMEV depletion and supplementation were initiated after mice were weaned. Here, we used a genetics approach for assessing effects of sMEV depletion on the development of suckling mice. Newborn C57BL/6J pups were fostered to Tumor Susceptibility Gene 101 (Tsg101) mammary-specific knockout (KO) dams or C57BL/6J dams (controls) in synchronized pregnancies. Tsg101 KO was associated with an 80% decrease of sMEVs. Postnatal weight gain and gut health (histology, morphology, and barrier function) were assessed until weaning at age three weeks. We observed a significant decrease in weight gain, length of small intestine, villi height, crypt depth, and intestinal barrier function in male and female pups fostered to Tsg101 dams compared to pups fostered to control dams. The effect size varied between 11 and 32 percent. Maternal Tsg101 KO did not affect the dams’ health, content of macronutrients and dry mass of milk and had no effect on the amount of milk consumed by pups. We conclude that sMEVs are important for growth and gut health in neonate mice.

母乳中每毫升含有 2.2 ± 1.5×1011 个细胞外小泡 (sEV)，800 毫升母乳中婴儿每天摄入 1.7×1014 个牛奶小泡 (sMEV)。婴儿配方奶粉中含有微量的 sMEVs。迄今为止，已有八项关于牛奶消耗的不良影响和五项关于补充 sMEV 的有益影响的报道，其中包括对婴儿和新生小鼠的研究。配方奶喂养的婴儿并不能从 sMEVs 中获益。迄今为止报道的大多数表型研究都有一个局限性，即小鼠断奶后才开始消耗和补充 sMEV。在此，我们采用遗传学方法来评估sMEV消耗对哺乳小鼠发育的影响。新生 C57BL/6J 幼鼠由肿瘤易感基因 101（Tsg101）乳腺特异性基因敲除（KO）母鼠或 C57BL/6J 母鼠（对照组）同步哺育。Tsg101 KO与sMEVs减少80%有关。对出生后体重增加和肠道健康（组织学、形态学和屏障功能）进行了评估，直到三周大时断奶。我们观察到，与对照组母鼠的幼崽相比，Tsg101母鼠寄养的雄性和雌性幼崽的体重增加、小肠长度、绒毛高度、隐窝深度和肠道屏障功能都明显下降。效应大小在 11% 到 32% 之间。母体 Tsg101 KO 不会影响母体的健康、宏量营养素含量和干奶质量，也不会影响幼崽的吃奶量。我们的结论是，sMEVs 对新生小鼠的生长和肠道健康非常重要。

{"title":"Tsg101 knockout in the mammary gland leads to a decrease in small extracellular vesicles in milk from C57BL/6J dams and contributes to leakiness of the gut mucosa and reduced postnatal weight gain in suckling pups","authors":"Javaria Munir , Mahrou Sadri , Janos Zempleni","doi":"10.1016/j.jnutbio.2024.109782","DOIUrl":"10.1016/j.jnutbio.2024.109782","url":null,"abstract":"<div><div>Human milk contains 2.2 ± 1.5×10<sup>11</sup> small extracellular vesicles (sEVs) per milliliter and human infants consume 1.7×10<sup>14</sup> milk sEVs (sMEVs) daily in 800 mL milk. Infant formula contains trace amounts of sMEVs. To date, eight adverse effects of milk depletion and five beneficial effects of sMEV supplementation have been reported including studies in infants and neonate mice. Formula-fed infants do not realize the benefits of sMEVs. Most of the phenotyping studies reported to date have the limitation that sMEV depletion and supplementation were initiated after mice were weaned. Here, we used a genetics approach for assessing effects of sMEV depletion on the development of suckling mice. Newborn C57BL/6J pups were fostered to Tumor Susceptibility Gene 101 (<em>Tsg101</em>) mammary-specific knockout (KO) dams or C57BL/6J dams (controls) in synchronized pregnancies. <em>Tsg101</em> KO was associated with an 80% decrease of sMEVs. Postnatal weight gain and gut health (histology, morphology, and barrier function) were assessed until weaning at age three weeks. We observed a significant decrease in weight gain, length of small intestine, villi height, crypt depth, and intestinal barrier function in male and female pups fostered to <em>Tsg101</em> dams compared to pups fostered to control dams. The effect size varied between 11 and 32 percent. Maternal <em>Tsg101</em> KO did not affect the dams’ health, content of macronutrients and dry mass of milk and had no effect on the amount of milk consumed by pups. We conclude that sMEVs are important for growth and gut health in neonate mice.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109782"},"PeriodicalIF":4.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468106","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

Preventive and therapeutic effects of molecular iodine in a model of diabetes mellitus induced by streptozotocin 分子碘在链脲佐菌素诱导的糖尿病模型中的预防和治疗作用：针对葡萄糖变化的碘疗法。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-16 DOI: 10.1016/j.jnutbio.2024.109783

Julia Rodríguez-Castelán , Evangelina Delgado-González , Mónica Sánchez-Tapia , Brenda Anguiano , Nimbe Torres , Carmen Aceves

Diabetes mellitus (DM) is a multifactorial condition that involves oxidative alterations and dysbiosis of the gut microbiota associated with an imbalance in glucose metabolism. Therefore, the need to develop integrative therapies that are both effective and have fewer side effects has become evident in recent years. Molecular iodine (I₂) has antioxidant effects in preclinical hyperglycemic models. The present work analyzes the preventive and therapeutic effects of oral I₂ supplementation in a DM model induced by low doses of streptozotocin (STZ). Male CD1 mice (12 weeks old) were divided into the following groups: control, STZ (20 mg/kg/day, i.p., for 5 days), I₂ (0.2 mg/Kg in drinking water), preventive (STZ + I₂), and therapeutic (I₂ supplementation from day 35 to day 90; STZ + I_2(Ther)). The supplementation with I₂ prevented and normalized hyperglycemia, hypercholesterolemia, and hypertriglyceridemia associated with STZ, preserving pancreatic, liver, muscle, and adipose tissue morphology and normalizing inflammatory gene induction (TLR2, TLR4, NFkβ, TNFα) in several tissues. Furthermore, compared to the STZ group, the presence of I₂ favored a more significant abundance of beneficial bacteria that support the integrity of the intestinal epithelial barrier and higher α-diversity. In conclusion, the I₂ supplement has preventive and therapeutic effects, reducing oxidative damage and reestablishing microbiota diversity following STZ exposure.

糖尿病（DM）是一种多因素疾病，涉及与葡萄糖代谢失衡相关的氧化改变和微生物群失调。因此，近年来，开发有效且副作用较少的综合疗法的需求已变得十分明显。分子碘（I2）在临床前高血糖模型中具有抗氧化作用。本研究分析了在低剂量链脲佐菌素（STZ）诱导的糖尿病模型中口服碘2的预防和治疗作用。雄性 CD1 小鼠（12 周大）被分为以下几组：对照组、STZ 组（20 毫克/千克/天，静脉注射，连续五天）、I2 组（0.2 毫克/千克，加入饮用水中）、预防组（STZ + I2）和治疗组（从第 35 天到第 90 天补充 I2；STZ + I2(Ther)）。补充 I2 可预防 STZ 引起的高血糖、高胆固醇血症和高甘油三酯血症，并使之恢复正常，还能保护胰腺、肝脏、肌肉和脂肪组织的形态，并使多个组织的炎症基因诱导（TLR2、TLR4、NFkβ、TNFα）恢复正常。此外，与 STZ 组相比，I2 的存在有利于增加有益菌的数量，从而支持肠上皮屏障的完整性和更高的α-多样性。总之，在接触 STZ 后，I2 补充剂具有预防和治疗作用，可减少氧化损伤并重建微生物群的多样性。

{"title":"Preventive and therapeutic effects of molecular iodine in a model of diabetes mellitus induced by streptozotocin","authors":"Julia Rodríguez-Castelán , Evangelina Delgado-González , Mónica Sánchez-Tapia , Brenda Anguiano , Nimbe Torres , Carmen Aceves","doi":"10.1016/j.jnutbio.2024.109783","DOIUrl":"10.1016/j.jnutbio.2024.109783","url":null,"abstract":"<div><div>Diabetes mellitus (DM) is a multifactorial condition that involves oxidative alterations and dysbiosis of the gut microbiota associated with an imbalance in glucose metabolism. Therefore, the need to develop integrative therapies that are both effective and have fewer side effects has become evident in recent years. Molecular iodine (I<sub>2</sub>) has antioxidant effects in preclinical hyperglycemic models. The present work analyzes the preventive and therapeutic effects of oral I<sub>2</sub> supplementation in a DM model induced by low doses of streptozotocin (STZ). Male CD1 mice (12 weeks old) were divided into the following groups: control, STZ (20 mg/kg/day, i.p., for 5 days), I<sub>2</sub> (0.2 mg/Kg in drinking water), preventive (STZ + I<sub>2</sub>), and therapeutic (I<sub>2</sub> supplementation from day 35 to day 90; STZ + I<sub>2(Ther)</sub>). The supplementation with I<sub>2</sub> prevented and normalized hyperglycemia, hypercholesterolemia, and hypertriglyceridemia associated with STZ, preserving pancreatic, liver, muscle, and adipose tissue morphology and normalizing inflammatory gene induction (TLR2, TLR4, NFkβ, TNFα) in several tissues. Furthermore, compared to the STZ group, the presence of I<sub>2</sub> favored a more significant abundance of beneficial bacteria that support the integrity of the intestinal epithelial barrier and higher α-diversity. In conclusion, the I<sub>2</sub> supplement has preventive and therapeutic effects, reducing oxidative damage and reestablishing microbiota diversity following STZ exposure.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109783"},"PeriodicalIF":4.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of selenium supply function of selenoprotein p through adduct formation by sulforaphane 红豆杉通过加合物形成抑制硒蛋白 P 的供硒功能

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-16 DOI: 10.1016/j.jnutbio.2024.109781

Xinying Ye , Takashi Toyama , Wang Yinuo, Runa Kudo, Siu Stephanie, Kotoko Arisawa, Yoshiro Saito

Selenium is a potent nucleophile essential for selenoenzymes, such as glutathione peroxidase (also known as GSH-Px; GPX; GPx) and selenoprotein P (also known as SelP; SEPP1; SELENOP; SeP). SeP is predominantly secreted from the liver and functions as a selenium carrier in plasma. We previously found that sulforaphane (SFN), an electrophilic phytochemical, reduces SeP production in cultured hepatocytes and mouse liver, however, the effect of electrophilic modification of SeP by SFN on selenium transport and metabolism remains unclear. In the present study, we demonstrate that sulforaphane covalently modifies selenocysteine/cysteine residues of SeP using an acidic biotin PAEC₅ maleimide labeling assay, which allows for focused-labeling of selenocysteine residues. Although the SFN-SeP adduct can be taken up by HepG2 cells and degraded by the lysosome, it was less effective in inducing GPx expression. Our findings indicate that SFN disrupts the selenium supply pathway through the formation of the SeP-SFN adduct.

硒是一种强效亲核素，是谷胱甘肽过氧化物酶（又称 GSH-Px；GPX；GPx）和硒蛋白 P（又称 SelP；SEPP1；SELENOP；SeP）等硒酶所必需的。SeP 主要从肝脏分泌，在血浆中起硒载体的作用。我们之前发现，亲电植物化学物质 sulforaphane 可减少培养肝细胞和小鼠肝脏中 SeP 的产生，但 SFN 对 SeP 的亲电修饰对硒转运和代谢的影响仍不清楚。在本研究中，我们利用酸性生物素 PAEC5 马来酰亚胺标记法对硒代半胱氨酸残基进行了集中标记，结果表明苏拉环能共价修饰 SeP 的硒代半胱氨酸/半胱氨酸残基。虽然 SFN-SeP 加合物能被 HepG2 细胞吸收并被溶酶体降解，但它在诱导 GPx 表达方面的效果较差。我们的研究结果表明，SFN 通过形成 SeP-SFN 加合物破坏了硒的供应途径。

{"title":"Inhibition of selenium supply function of selenoprotein p through adduct formation by sulforaphane","authors":"Xinying Ye , Takashi Toyama , Wang Yinuo, Runa Kudo, Siu Stephanie, Kotoko Arisawa, Yoshiro Saito","doi":"10.1016/j.jnutbio.2024.109781","DOIUrl":"10.1016/j.jnutbio.2024.109781","url":null,"abstract":"<div><div>Selenium is a potent nucleophile essential for selenoenzymes, such as glutathione peroxidase (also known as GSH-Px; GPX; GPx) and selenoprotein P (also known as SelP; SEPP1; SELENOP; SeP). SeP is predominantly secreted from the liver and functions as a selenium carrier in plasma. We previously found that sulforaphane (SFN), an electrophilic phytochemical, reduces SeP production in cultured hepatocytes and mouse liver, however, the effect of electrophilic modification of SeP by SFN on selenium transport and metabolism remains unclear. In the present study, we demonstrate that sulforaphane covalently modifies selenocysteine/cysteine residues of SeP using an acidic biotin PAEC<sub>5</sub> maleimide labeling assay, which allows for focused-labeling of selenocysteine residues. Although the SFN-SeP adduct can be taken up by HepG2 cells and degraded by the lysosome, it was less effective in inducing GPx expression. Our findings indicate that SFN disrupts the selenium supply pathway through the formation of the SeP-SFN adduct.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109781"},"PeriodicalIF":4.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Luteolin alleviates muscle atrophy, mitochondrial dysfunction and abnormal FNDC5 expression in high fat diet-induced obese rats and palmitic acid-treated C2C12 myotubes 木犀草素能缓解高脂饮食诱导的肥胖大鼠和棕榈酸处理的 C2C12 肌细胞的肌肉萎缩、线粒体功能障碍和 FNDC5 表达异常。

IF 4.8 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Nutritional Biochemistry

Pub Date : 2024-10-11 DOI: 10.1016/j.jnutbio.2024.109780

Yiyuan Zhang, Chunyun Luo, Puxin Huang, Yahong Cheng, Yufang Ma, Jiefang Gao, Hong Ding

Obesity is associated with a series of skeletal muscle impairments and dysfunctions, which are characterized by metabolic disturbances and muscle atrophy. Luteolin is a phenolic phytochemical with broad pharmacological activities. The present study aimed to evaluate the protective effects of Luteolin on muscle function and explore the potential mechanisms in high-fat diet (HFD)-induced obese rats and palmitic acid (PA)-treated C2C12 myotubes. Male Sprague-Dawley (SD) rats were fed with a control diet or HFD and orally administrated 0.5% sodium carboxymethyl cellulose (vehicle) or Luteolin (25, 50, and 100 mg/kg, respectively) for 12 weeks. The results showed that Luteolin ameliorated HFD-induced body weight gain, glucose intolerance and hyperlipidemia. Luteolin also alleviated muscle atrophy, decreased ectopic lipid deposition and prompted muscle-fiber-type conversion in the skeletal muscle. Meanwhile, we observed an evident improvement in mitochondrial quality control and respiratory capacity, accompanied by reduced oxidative stress. Mechanistic studies indicated that AMPK/SIRT1/PGC-1α signaling pathway plays a key role in the protective effects of Luteolin on skeletal muscle in the obese states, which was further verified by using specific inhibitors of AMPK and SIRT1. Moreover, the mRNA expression levels of markers in brown adipocyte formation were significantly up-regulated post Luteolin supplementation in different adipose depots. Taken together, these results revealed that Luteolin supplementation might be a promising strategy to prevent obesity-induced loss of mass and biological dysfunctions of skeletal muscle.

肥胖与一系列骨骼肌损伤和功能障碍有关，其特点是代谢紊乱和肌肉萎缩。木犀草素是一种酚类植物化学物质，具有广泛的药理活性。本研究旨在评估木犀草素对高脂饮食（HFD）诱导的肥胖大鼠和棕榈酸（PA）处理的 C2C12 肌管肌肉功能的保护作用，并探索其潜在机制。雄性斯普拉格-道利（SD）大鼠以对照组饮食或高脂饮食喂养，并口服 0.5% 羧甲基纤维素钠（载体）或木犀草素（分别为 25、50 和 100 mg/kg）12 周。结果表明，木犀草素可改善高纤维食物诱导的体重增加、糖耐量减低和高脂血症。木犀草素还能缓解肌肉萎缩，减少异位脂质沉积，促进骨骼肌肌纤维型转化。同时，我们观察到线粒体质量控制和呼吸能力得到明显改善，氧化应激也有所降低。机理研究表明，在木犀草素对肥胖状态下骨骼肌的保护作用中，AMPK/SIRT1/PGC-1α 信号通路起着关键作用。此外，补充叶黄素后，棕色脂肪细胞形成标志物的 mRNA 表达水平在不同脂肪贮备中均显著上调。综上所述，这些结果表明，补充木犀草素可能是预防肥胖引起的骨骼肌质量下降和生物功能障碍的一种有效策略。

{"title":"Luteolin alleviates muscle atrophy, mitochondrial dysfunction and abnormal FNDC5 expression in high fat diet-induced obese rats and palmitic acid-treated C2C12 myotubes","authors":"Yiyuan Zhang, Chunyun Luo, Puxin Huang, Yahong Cheng, Yufang Ma, Jiefang Gao, Hong Ding","doi":"10.1016/j.jnutbio.2024.109780","DOIUrl":"10.1016/j.jnutbio.2024.109780","url":null,"abstract":"<div><div>Obesity is associated with a series of skeletal muscle impairments and dysfunctions, which are characterized by metabolic disturbances and muscle atrophy. Luteolin is a phenolic phytochemical with broad pharmacological activities. The present study aimed to evaluate the protective effects of Luteolin on muscle function and explore the potential mechanisms in high-fat diet (HFD)-induced obese rats and palmitic acid (PA)-treated C2C12 myotubes. Male Sprague-Dawley (SD) rats were fed with a control diet or HFD and orally administrated 0.5% sodium carboxymethyl cellulose (vehicle) or Luteolin (25, 50, and 100 mg/kg, respectively) for 12 weeks. The results showed that Luteolin ameliorated HFD-induced body weight gain, glucose intolerance and hyperlipidemia. Luteolin also alleviated muscle atrophy, decreased ectopic lipid deposition and prompted muscle-fiber-type conversion in the skeletal muscle. Meanwhile, we observed an evident improvement in mitochondrial quality control and respiratory capacity, accompanied by reduced oxidative stress. Mechanistic studies indicated that AMPK/SIRT1/PGC-1α signaling pathway plays a key role in the protective effects of Luteolin on skeletal muscle in the obese states, which was further verified by using specific inhibitors of AMPK and SIRT1. Moreover, the mRNA expression levels of markers in brown adipocyte formation were significantly up-regulated post Luteolin supplementation in different adipose depots. Taken together, these results revealed that Luteolin supplementation might be a promising strategy to prevent obesity-induced loss of mass and biological dysfunctions of skeletal muscle.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"135 ","pages":"Article 109780"},"PeriodicalIF":4.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468095","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