ACOT1
- Known as:
- ACOT1
- Catalog number:
- 001016A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ACOT1
Related genes to: ACOT1
- Gene:
- ACOT1 NIH gene
- Name:
- acyl-CoA thioesterase 1
- Previous symbol:
- -
- Synonyms:
- ACH2, CTE-1, LACH2
- Chromosome:
- 14q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 2006-08-30
- Date modifiied:
- 2014-11-18
Related products to: ACOT1
Related articles to: ACOT1
- Diabetic cardiomyopathy (DCM) is a serious cardiovascular complication specific to diabetes mellitus, with rising global prevalence. Ferroptosis, an iron-dependent form of regulated cell death driven by lethal lipid peroxidation, has been implicated in the pathogenesis of DCM. However, the key regulatory genes remain poorly characterized. This study aimed to identify and validate ferroptosis-related signature genes in DCM. Three murine transcriptomic datasets (GSE123975, GSE155377, and GSE210611) were retrieved from GEO and merged after batch correction. Differentially expressed genes were intersected with weighted gene co-expression network analysis disease-associated module genes and FerrDb ferroptosis annotations to define the ferroptosis-related differentially expressed gene candidate pool. LASSO regression and random forest selection then prioritized hub genes, defined operationally as candidates consistently prioritized by both machine-learning algorithms rather than by network-topological centrality. Classification performance was evaluated by ROC analysis and validated in two independent cohorts (GSE161931 and GSE274500). mMCPcounter estimated immune and stromal infiltration. ScRNA-seq (GSE290095) and spatial transcriptomic (GSE290094) profiling characterized cellular distribution, predicted cardiomyocyte network perturbations and tissue-level expression patterns. High-fat diet/streptozotocin (HFD/STZ)-induced DCM rat models provided experimental validation. and were identified as hub genes, with strong discriminatory performance in the discovery cohort (AUC = 1.000 and 0.988; in-sample estimates, = 26) and independent external validation (AUC = 0.951 and 0.988). Immune profiling linked both genes inversely with vessel scores, and was also linked with eosinophils. Single-cell analysis localized enrichment to cardiomyocytes and endothelial cells, while was broadly expressed across multiple cell types, with elevated levels in DCM. In silico knockout analysis predicted distinct cardiomyocyte network perturbation profiles for and , and spatial transcriptomics revealed modest but disease-specific spatial associations between hub gene expression and ferroptosis driver scores (: rho = 0.123; : rho = 0.154). Both genes were significantly upregulated at mRNA and protein levels in HFD/STZ-induced DCM rats, with concurrent GPX4 depletion, ACSL4 accumulation, and FTH1 reduction consistent with ferroptosis activation. This study identifies and as ferroptosis-related molecular signatures in DCM and provides multistep prioritization and validation spanning bulk transcriptomics, single-cell and spatial transcriptomics, and in vivo experimental verification, offering potential targets for ferroptosis-targeted therapeutic intervention. - Source: PubMed
Publication date: 2026/09/09
Zhou FengZhou Jia-BinZhang LingYan Yi-QingWu DanWei Tian-PengZhang Zhen-YeLiu Huan-HuanShen Jun-XianLiu YingQian Ling-LingWang Ru-Xing - Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of all heart failure cases worldwide, yet effective targeted therapies remain limited. Tectorigenin (Tec), a bioactive isoflavone derived from traditional Chinese medicine, exhibits diverse cardioprotective effects; however, its therapeutic potential and underlying mechanisms in HFpEF remain incompletely understood. This study aimed to investigate the effects of Tec on HFpEF and elucidate the underlying molecular mechanisms. A mouse model of HFpEF was established using the "two-hit" approach (high-fat diet + L-NAME). In vivo experiments included echocardiography, histological staining, treadmill testing, metabolic assessments, and molecular analyses. In vitro, neonatal rat ventricular myocytes (NRVMs) exposed to palmitic acid (PA) were used to model cardiomyocyte lipotoxicity. RNA sequencing, network pharmacology, molecular docking, surface plasmon resonance, pull-down assays, chromatin immunoprecipitation, and gene silencing were employed to elucidate the regulatory mechanisms. Tec attenuated HFpEF progression and retained therapeutic efficacy when administered after HFpEF establishment. In vitro, Tec alleviated PA-induced cardiomyocyte lipotoxicity. Mechanistically, Tec directly bound EGFR at the E762/M793 sites and inhibited its aberrant activation. Inhibition of EGFR signaling suppressed the downstream EGFR-EGR2 axis, thereby upregulating Acot1 and improving myocardial lipid metabolic homeostasis. Cardiac-specific Acot1 knockdown or pharmacological activation of EGFR markedly attenuated Tec-mediated improvements in cardiac function, remodeling, and myocardial lipid metabolism. Tec ameliorates HFpEF through the EGFR-EGR2-Acot1 axis, highlighting a potential therapeutic strategy for HFpEF. - Source: PubMed
Publication date: 2026/09/18
Wang Li-GuoLin KeYou Meng-ZhenLi Qin-FengWei Wen-JieLi HuiShi YiYan Yu-FengLi RanWang Mei-HuiXia Chun-LeiFu Guo-ShengXu Ya-Ting - Sepsis associated acute liver injury is a major contributor to multiple organ dysfunction and mortality in critically ill patients. ACOT1 has emerged as a promising therapeutic target, demonstrated to inhibit disseminated intravascular coagulation through its anti-ferroptosis activity. However, its specific function and mechanistic role in the context of during endotoxemia-induced liver injury have not been elucidated. This study demonstrates that ferroptosis was markedly activated in both lipopolysaccharide (LPS)-stimulated AML12 hepatocytes and LPS-induced acute liver injury mouse models. RNA sequencing and bioinformatics analyses identified ACOT1 as the most significantly downregulated genes following LPS stimulation. Functionally, ACOT1 overexpression upregulated GPX4 and SLC7A11 expression, reduced mitochondrial ROS and Fe accumulation, which ultimately attenuated LPS-induced hepatocyte ferroptosis. Mechanistically, ACOT1 overexpression activated PPARγ, thus suppressing NF-κB pathway activation and inflammatory responses thereafter. IP-MS and immunofluorescence staining confirmed that SLC25A5 interacts with ACOT1 and functions as a molecular partner in regulating hepatocyte ferroptosis by reducing mitochondrial ROS and Fe levels. Protein interaction analysis between ACOT1 and SLC25A5 showed a Rosetta score of -271.16 kcal/mol, indicating strong binding affinity. Collectively, our results identified ACOT1 as a novel inhibitor of ferroptosis in LPS-induced acute liver injury. ACOT1 exerts protective effects by modulating the PPARγ/NF-κB signaling axis and cooperating with SLC25A5 to regulate oxidative stress-driven ferroptosis. These results highlight ACOT1 as a potential regulator for inflammatory liver injury. - Source: PubMed
Publication date: 2026/08/01
Xu ChengzhuWang ShunWang XiyangZhang XuanOuyang SuxiaHuang TingxuanJin DanqunZhang LeXu Yuanyuan - Diabetic cardiomyopathy (DCM) is a critical pathological driver of heart failure in diabetic patients, primarily characterized by progressive myocardial fibrosis. Nevertheless, the core molecular network linking upstream metabolic dysregulation to the aberrant activation of downstream cardiac fibroblasts remains largely elusive. In this study, we combined in vivo and in vitro approaches with bioinformatics analysis. A high-fat diet-induced mouse model of diabetic myocardial fibrosis was established, and transcriptome sequencing was performed to screen for hub genes, which were subsequently validated in two independent DCM datasets. Single-cell RNA sequencing revealed that PDK4 and ACOT1 were upregulated in cardiac fibroblasts under pathological conditions. In vitro experiments confirmed that high glucose induced the expression of PDK4, ACOT1, and fibrotic markers in human primary cardiac fibroblasts. Molecular docking predicted a potential interaction between PDK4 and ACOT1. Collectively, our findings identify PDK4 and ACOT1 as evolutionarily conserved metabolic hub genes associated with myocardial fibrosis in DCM, suggesting a putative "metabolism-fibrosis axis" and providing potential therapeutic targets. - Source: PubMed
Liu HuanQi GuanmingOuyang ShengrongMa Feifei - As a fat-soluble vitamin, vitamin E (VE) is prone to suboptimal intake in the general population. Alpha-tocopherol (α-TE) represents the most biologically significant form of VE in vivo. Nevertheless, the potential detrimental effects of α-TE deficiency on health remain unclear. This study was conducted to investigate the effect of α-TE deficiency on hepatic metabolism and gut microbiota. C57BL/6J mice were randomly assigned to receive one of three dietary regimens: a α-TE-deficient diet, a control diet with normal α-TE, or a high-dose diet containing four times the normal α-TE level. Histopathology, serum biochemistry, RNA-Seq, RT-qPCR, Western blot, and 16S rRNA gene sequencing with correlation analysis were used to assess metabolic phenotypes, hepatic circadian, hepatic lipid metabolism, and cecal microbiota, respectively. The results demonstrated that α-TE deficiency induced hepatic steatosis and lipid metabolic disturbances. α-TE deficiency significantly decreased Arntl and Clock expression, but increased Per2. Additionally, it upregulated the expression of lipogenic genes such as , and and simultaneously downregulated fatty acid oxidation genes such as , and , bringing about imbalance in lipid homeostasis. In addition, α-TE deficiency greatly changed the structure and composition of gut microbiota. Bacterial genera like , , , , and were significantly correlated with hepatic circadian and lipid metabolism gene expression with the strongest correlation being . This work is the first to reveal that short term α-TE deficiency could cause lipid metabolic disorder via the "gut microbiota-liver circadian clock" axis, which provides novel insights into the etiology of nutrition-related metabolic diseases and targets for nutritional intervention. - Source: PubMed
Publication date: 2026/06/09
Peng LeiZhao YanFan YuqinPeng QiSheng JunTian YangGao Xiaoyu