Redox Report最新文献

{"title":"TOM5 regulates the mitochondrial membrane potential of alveolar epithelial cells in organizing pneumonia.","authors":"Yan Qian, Xiao Li, Xinyu Li, Xijie Zhang, Qi Yuan, Zhengxia Wang, Minghun Zhang, Mao Huang, Ningfei Ji","doi":"10.1080/13510002.2024.2354625","DOIUrl":"10.1080/13510002.2024.2354625","url":null,"abstract":"<p><p>Deficiency of TOM5, a mitochondrial protein, causes organizing pneumonia (OP) in mice. The clinical significance and mechanisms of TOM5 in the pathogenesis of OP remain elusive. We demonstrated that TOM5 was significantly increased in the lung tissues of OP patients, which was positively correlated with the collagen deposition. In a bleomycin-induced murine model of chronic OP, increased TOM5 was in line with lung fibrosis. In vitro, TOM5 regulated the mitochondrial membrane potential in alveolar epithelial cells. TOM5 reduced the proportion of early apoptotic cells and promoted cell proliferation. Our study shed light on the roles of TOM5 in OP.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11134018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective effects of liposomal resveratrol in diabetic rats: unveiling antioxidant and anti-inflammatory benefits.","authors":"Ahmed Z Alanazi, Mohammed Alqinyah, Abdullah S Alhamed, Hanan Mohammed, Mohammad Raish, Khaldoon Aljerian, Jawza F Alsabhan, Khalid Alhazzani","doi":"10.1080/13510002.2024.2416835","DOIUrl":"10.1080/13510002.2024.2416835","url":null,"abstract":"<p><p>As a consequence of chronic hyperglycemia, diabetes complications and tissue damage are exacerbated. There is evidence that natural phytochemicals, including resveratrol, a bioactive polyphenol, may be able to reduce oxidative stress and improve insulin sensitivity. However, resveratrol's limited bioavailability hampers its therapeutic effectiveness. By using liposomes, resveratrol may be better delivered into the body and be more bioavailable. The objective of this study was to assess the cardioprotective potential of liposome-encapsulated resveratrol (LR) in a streptozotocin-induced (STZ) diabetic rat model. Adult male Wistar rats were categorized into five groups: control, diabetic, resveratrol-treated (40 mg/kg), liposomal resveratrol (LR)-treated (20 mg/kg) and liposomal resveratrol (LR)-treated (40 mg/kg) for a five-week study period. We compared the effects of LR to those of resveratrol (40 mg/kg) on various parameters, including serum levels of cardiac markers, tissue levels of pro-inflammatory cytokines, nuclear transcription factor, oxidative stress markers, and apoptotic markers. LR treatment in STZ-diabetic rats resulted in notable physiological improvements, including blood glucose regulation, inflammation reduction, oxidative stress mitigation, and apoptosis inhibition. LR effectively lowered oxidative stress and enhanced cardiovascular function. It also demonstrated a remarkable ability to suppress NF-kB-mediated inflammation by inhibiting the pro-inflammatory cytokines TNF-α and IL-6. Additionally, LR restored the antioxidant enzymes, catalase and glutathione peroxidase, thereby effectively counteracting oxidative stress. Notably, LR modulated apoptotic regulators, including caspase, Bcl2, and Bax, suggesting a role in regulating programmed cell death. These biochemical alterations were consistent with improved structural integrity of cardiac tissue as revealed by histological examination. In comparison, resveratrol exhibited lower efficacy at an equivalent dosage. Liposomal resveratrol shows promise in alleviating hyperglycemia-induced cardiac damage in diabetes. Further research is warranted to explore its potential as a therapeutic agent for diabetic cardiovascular complications and possible cardioprotective effects.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol relieves myocardial ischemia-reperfusion injury through inhibiting AKT nitration modification.","authors":"Lei Li, Jiantao Wang, Dandan Zhang, Li Deng, Xudong Zhao, Chunqing Wang, Xianliang Yan, Shuqun Hu","doi":"10.1080/13510002.2024.2420564","DOIUrl":"10.1080/13510002.2024.2420564","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to clarify whether Protein kinase B (PKB)/AKT is nitrated in myocardial ischemia and reperfusion injury (MIRI) resveratrol (RSV)'s protective effect during this process.</p><p><strong>Methods: </strong>We blocked blood flow of the left coronary artery (LAD) of mice and used H9c2 cells under an oxygen-glucose deprivation (OGD) environment as animal and cell models of MIRI. N-methyl-D-aspartic acid receptor (NMDAR) inhibitor MK801, neuronal nitric oxide synthase (nNOS) inhibitor 7-NI and RSV were used as interventions. Nitration of proteins, infarction area, cardiomyocyte apoptosis and AKT nitration sites were detected during this study.</p><p><strong>Results: </strong>During <i>in-vivo</i> study, AKT nitration was induced through the NMDAR/nNOS/peroxynitrite (ONOO^-) pathway, leading to decreased phosphorylation of AKT and increased cardiomyocyte apoptosis. AKT nitration was decreased and phosphorylation was elevated when administrated with RSV, MK801 and 7-NI. In <i>in-vitro</i> study, AKT nitration and TUNEL positive cells was elevated when administrated with NO donor H9c2 cells after OGD/R, when administrated with RSV, MK801 and 7-NI, AKT nitration and apoptosis was deceased in H9c2 cells. Mass spectrometry revealed that nitration sites of AKT included 14 Tyrosine residues.</p><p><strong>Discussion: </strong>RSV could inhibit AKT nitration and elevated phosphorylation through suppressing NMDAR/nNOS/ONOO^- pathway and further reduce the apoptosis of cardiomyocytes in of myocardial I/R.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implication of endoplasmic reticulum stress and mitochondrial perturbations in remote liver injury after renal ischemia/reperfusion in rats: potential protective role of azilsartan.","authors":"Rania A Elrashidy, Esraa M Zakaria, Rehab A Hasan, Asmaa M Elmaghraby, Dina A Hassan, Ranya M Abdelgalil, Shaimaa R Abdelmohsen, Amira M Negm, Azza S Khalil, Ayat M S Eraque, Reem M Ahmed, Walaa S Sabbah, Ahmed A Ahmed, Samah E Ibrahim","doi":"10.1080/13510002.2024.2319963","DOIUrl":"10.1080/13510002.2024.2319963","url":null,"abstract":"<p><p><b>Objectives:</b> Distant liver injury is a complication of renal ischemia-reperfusion (I/R) injury, which imposes mortality and economic burden. This study aimed to elucidate the cross-talk of endoplasmic reticulum (ER) stress and mitochondrial perturbations in renal I/R-induced liver injury, and the potential hepatoprotective effect of azilsartan (AZL).<b>Methods:</b> Male albino Wister rats were pre-treated with AZL (3 mg/kg/day, PO) for 7 days then a bilateral renal I/R or sham procedure was performed. Activities of liver enzymes were assessed in plasma. The structure and ultra-structure of hepatocytes were assessed by light and electron microscopy. Markers of ER stress, mitochondrial biogenesis and apoptosis were analyzed in livers of rats.<b>Results:</b> Renal ischemic rats showed higher plasma levels of liver enzymes than sham-operated rats, coupled with histological and ultra-structural alterations in hepatocytes. Mechanistically, there was up-regulation of ER stress markers and suppression of mitochondrial biogenesis-related proteins and enhanced apoptosis in livers of renal ischemic rats. These abnormalities were almost abrogated by AZL pretreatment.<b>Discussion:</b> Our findings uncovered the involvement of mitochondrial perturbations, ER stress and apoptosis in liver injury following renal I/R, and suggested AZL as a preconditioning strategy to ameliorate remote liver injury in patients susceptible to renal I/R after adequate clinical testing.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139973332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions.","authors":"Hai-Yu Mo, Ruo-Bing Wang, Meng-Yao Ma, Yi Zhang, Xin-Yu Li, Wang-Rong Wen, Yi Han, Tian Tian","doi":"10.1080/13510002.2024.2345455","DOIUrl":"10.1080/13510002.2024.2345455","url":null,"abstract":"<p><strong>Objectives: </strong>Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress.</p><p><strong>Methods: </strong>ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo.</p><p><strong>Results: </strong>We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models.</p><p><strong>Discussion: </strong>our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11086033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperglycemia-induced oxidative stress exacerbates mitochondrial apoptosis damage to cochlear stria vascularis pericytes via the ROS-mediated Bcl-2/CytC/AIF pathway.","authors":"Tian-Feng Shi, Zan Zhou, Wen-Jun Jiang, Tian-Lan Huang, Jun-Qiang Si, Li Li","doi":"10.1080/13510002.2024.2382943","DOIUrl":"10.1080/13510002.2024.2382943","url":null,"abstract":"<p><strong>Objectives: </strong>Diabetes is closely linked to hearing loss, yet the exact mechanisms remain unclear. Cochlear stria vascularis and pericytes (PCs) are crucial for hearing. This study investigates whether high glucose induces apoptosis in the cochlear stria vascularis and pericytes via elevated ROS levels due to oxidative stress, impacting hearing loss.</p><p><strong>Methods: </strong>We established a type II diabetes model in C57BL/6J mice and used auditory brainstem response (ABR), Evans blue staining, HE staining, immunohistochemistry, and immunofluorescence to observe changes in hearing, blood-labyrinth barrier (BLB) permeability, stria vascularis morphology, and apoptosis protein expression. Primary cultured stria vascularis pericytes were subjected to high glucose, and apoptosis levels were assessed using flow cytometry, Annexin V-FITC, Hoechst 33342 staining, Western blot, Mitosox, and JC-1 probes.</p><p><strong>Results: </strong>Diabetic mice showed decreased hearing thresholds, reduced stria vascularis density, increased oxidative stress, cell apoptosis, and decreased antioxidant levels. High glucose exposure increased apoptosis and ROS content in pericytes, while mitochondrial membrane potential decreased, with AIF and cytochrome C (CytC) released from mitochondria to the cytoplasm. Adding oxidative scavengers reduced AIF and CytC release, decreasing pericyte apoptosis.</p><p><strong>Discussion: </strong>Hyperglycemia may induce mitochondrial apoptosis of cochlear stria vascularis pericytes through oxidative stress.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamine sustains energy metabolism and alleviates liver injury in burn sepsis by promoting the assembly of mitochondrial HSP60-HSP10 complex via SIRT4 dependent protein deacetylation.","authors":"Yongjun Yang, Qian Chen, Shijun Fan, Yongling Lu, Qianyin Huang, Xin Liu, Xi Peng","doi":"10.1080/13510002.2024.2312320","DOIUrl":"10.1080/13510002.2024.2312320","url":null,"abstract":"<p><p>Burns and burn sepsis, characterized by persistent and profound hypercatabolism, cause energy metabolism dysfunction that worsens organ injury and systemic disorders. Glutamine (Gln) is a key nutrient that remarkably replenishes energy metabolism in burn and sepsis patients, but its exact roles beyond substrate supply is unclear. In this study, we demonstrated that Gln alleviated liver injury by sustaining energy supply and restoring redox balance. Meanwhile, Gln also rescued the dysfunctional mitochondrial electron transport chain (ETC) complexes, improved ATP production, reduced oxidative stress, and protected hepatocytes from burn sepsis injury. Mechanistically, we revealed that Gln could activate SIRT4 by upregulating its protein synthesis and increasing the level of Nicotinamide adenine dinucleotide (NAD⁺), a co-enzyme that sustains the activity of SIRT4. This, in turn, reduced the acetylation of shock protein (HSP) 60 to facilitate the assembly of the HSP60-HSP10 complex, which maintains the activity of ETC complex II and III and thus sustain ATP generation and reduce reactive oxygen species release. Overall, our study uncovers a previously unknown pharmacological mechanism involving the regulation of HSP60-HSP10 assembly by which Gln recovers mitochondrial complex activity, sustains cellular energy metabolism and exerts a hepato-protective role in burn sepsis.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Angelica keiskei</i> water extract Mitigates Age-Associated Physiological Decline in Mice.","authors":"Huan Liu, Gang Wei, Tongxing Wang, Yunlong Hou, Bin Hou, Xiaoyan Li, Chao Wang, Mingzhe Sun, Min Su, Zhifang Guo, Lu Wang, Ning Kang, Mengnan Li, Zhenhua Jia","doi":"10.1080/13510002.2024.2305036","DOIUrl":"10.1080/13510002.2024.2305036","url":null,"abstract":"<p><strong>Objective: </strong>Angelica keiskei is a medicinal and edible plant that has been reported to possess potent antioxidant properties in several in vitro models, but its effectiveness on naturally aging organisms is still lacking. This study explores the antioxidant and health-promoting effects of Angelica keiskei in naturally aging mice.</p><p><strong>Methods: </strong>We treated 48-week-old mice with Angelica keiskei water extract (AKWE) 30 days, and measured indicators related to aging and antioxidants. In addition, we conducted network pharmacology analysis, component-target molecular docking, real-time PCR, and MTS assays to investigate relevant factors.</p><p><strong>Results: </strong>The results indicated that administration of AKWE to mice led to decrease blood glucose levels, improve muscle fiber structure, muscle strength, gait stability, and increase levels of glutathione and superoxide dismutase in serum. Additionally, it decreased pigmentation of the heart tissues. Angelica keiskei combats oxidative stress by regulating multiple redox signaling pathways, and its ingredients Coumarin and Flavonoids have the potential to bind to SIRT3 and SIRT5.</p><p><strong>Conclusions: </strong>Our findings indicated the potential of Angelica keiskei as a safe and effective dietary supplement to combat aging and revealed the broad prospects of medicinal and edible plants for addressing aging and age-related chronic diseases.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nobiletin protects against alcohol-induced mitochondrial dysfunction and liver injury by regulating the hepatic NRF1-TFAM signaling pathway.","authors":"Dan Lu, Aiping Huang, Xiaoqing Tong, Xiaoyan Zhang, Songtao Li, Xiaolong Yu","doi":"10.1080/13510002.2024.2395779","DOIUrl":"10.1080/13510002.2024.2395779","url":null,"abstract":"<p><strong>Objectives: </strong>Alcohol and its metabolites, such as acetaldehyde, induced hepatic mitochondrial dysfunction play a pathological role in the development of alcohol-related liver disease (ALD).</p><p><strong>Methods: </strong>In this study, we investigated the potential of nobiletin (NOB), a polymethoxylated flavone, to counter alcohol-induced mitochondrial dysfunction and liver injury.</p><p><strong>Results: </strong>Our findings demonstrate that NOB administration markedly attenuated alcohol-induced hepatic steatosis, endoplasmic reticulum stress, inflammation, and tissue damage in mice. NOB reversed hepatic mitochondrial dysfunction and oxidative stress in both alcohol-fed mice and acetaldehyde-treated hepatocytes. Mechanistically, NOB restored the reduction of hepatic mitochondrial transcription factor A (TFAM) at both mRNA and protein levels. Notably, the protective effects of NOB against acetaldehyde-induced mitochondrial dysfunction and cell death were abolished in hepatocytes lacking <i>Tfam</i>. Furthermore, NOB administration reinstated the levels of hepatocellular NRF1, a key transcriptional regulator of TFAM, which were decreased by alcohol and acetaldehyde exposure. Consistent with these findings, hepatocyte-specific overexpression of <i>Nrf1</i> protected against alcohol-induced hepatic <i>Tfam</i> reduction, mitochondrial dysfunction, oxidative stress, and liver injury.</p><p><strong>Conclusions: </strong>Our study elucidates the involvement of the NRF1-TFAM signaling pathway in the protective mechanism of NOB against chronic-plus-binge alcohol consumption-induced mitochondrial dysfunction and liver injury, suggesting NOB supplementation as a potential therapeutic strategy for ALD.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice.","authors":"Jiani Lu, Zhengshan Tang, Miaomiao Xu, Jianqiang Lu, Fengmei Wang, Xin Ni, Changnan Wang, Bo Yu","doi":"10.1080/13510002.2024.2347139","DOIUrl":"10.1080/13510002.2024.2347139","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study was to investigate whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle <i>Cth</i> knockout (<i>Cth^Δskm</i>) mice.</p><p><strong>Methods: </strong>The <i>Cth</i>^<i>Δskm</i> mice and littermate <i>Cth-floxed</i> (<i>Cth^f/f</i>) mice were fed with either HFD or chow diet for 13 weeks. Metabolomics and transcriptome analysis were used to assess the impact of CTH deficiency in skeletal muscle.</p><p><strong>Results: </strong>Metabolomics coupled with transcriptome showed that <i>Cth^Δskm</i> mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in <i>Cth^f/f</i> mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. <i>Cth^Δskm</i>+HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to <i>Cth^f/f</i>+HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in <i>Cth^Δskm</i>+HFD mice. Omics analysis showed differential pathways enriched between <i>Cth^Δskm</i> mice and <i>Cth^f/f</i> mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in <i>Cth^Δskm</i>+HFD mice compared to <i>Cth^f/f</i>+HFD mice.</p><p><strong>Discussion: </strong>Our results indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}