更新于：2024-09-19

ACADL

更新于：2024-09-19

基本信息

别名

ACAD4、ACADL、acyl-CoA dehydrogenase long chain

+ [2]

简介

Long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (By similarity). The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA (By similarity). Among the different mitochondrial acyl-CoA dehydrogenases, long-chain specific acyl-CoA dehydrogenase can act on saturated and unsaturated acyl-CoAs with 6 to 24 carbons with a preference for 8 to 18 carbons long primary chains (PubMed:8823175, PubMed:21237683).

关联

100 项与 ACADL 相关的临床结果

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100 项与 ACADL 相关的转化医学

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0 项与 ACADL 相关的专利（医药）

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389

项与 ACADL 相关的文献（医药）

2024-10-01·Science of The Total Environment

Gestational organophosphate esters (OPEs) exposure in association with placental DNA methylation levels of peroxisome proliferator-activated receptors (PPARs) signaling pathway-related genes

Article

作者: Wang, Ziliang ; Song, Shujuan ; Song, Xiuxia ; Miao, Maohua ; Zhu, Haijun ; Wu, Qihan ; Yuan, Wei ; Huang, Baoqin ; Ji, Honglei ; Liang, Hong ; Chen, Yafei

BACKGROUNDOrganophosphate esters (OPEs) exposure could affect offspring health. However, the underlying mechanisms are not well documented.OBJECTIVESBased on a birth cohort study, we aimed to investigate the associations among gestational OPEs exposure, placental DNA methylation levels of peroxisome proliferator-activated receptor (PPAR) signaling pathway-related genes, and fetal growth.METHODSWe measured the concentrations of eight OPE metabolites in maternal urine samples and neonatal anthropometric measurements in 733 mother-child pairs. In 327 placental samples, we assessed the DNA methylation levels of 14 genes which were involved in the PPARs signaling pathway and expressed in placenta. Multiple linear regression models were used to examine the associations of OPEs exposure with placental DNA methylation, and of OPEs and placental DNA methylation with neonatal anthropometric measurements. Causal mediation analyses were conducted to examine the potential mediating role of placental DNA methylation in the pathway between OPEs exposure and fetal growth.RESULTSWe observed a general pattern of OPEs exposure being associated with hypermethylation of candidate genes, with statistically significant associations identified for several OPEs with RXRA, ACAA1, ACADL, ACADM, PLTP, and NR1H3 methylation. Further, gestational exposure to BCIPP, DPP, BBOEP, ∑NCl-OPEs, and ∑OPEs tended to be associated with lower anthropometric measurements, with more significant associations observed on arm circumference, and abdominal and back skinfold thickness. Notably, RXRA, ACAA1, ACOX1, CPT2, ACADM, and NR1H3 methylation tended to be associated with lower neonatal anthropometric measurements, especially for abdominal and back skinfold thickness. Moreover, mediation analyses showed that 19.42 % of the total effect of DPP on the back skinfold thickness was mediated by changes in RXRA methylation, and there was a significant indirect effect of RXRA methylation.CONCLUSIONSGestational OPEs exposure could disrupt the placental DNA methylation levels of PPAR signaling pathway-related genes, which might contribute to the effect of OPEs on fetal growth.

2024-08-06·ACS Omega

Proteomics Analysis Provides Insights into the Role of Lipid Metabolism in T2DM-Related Sarcopenia

Article

作者: Huang, Zhengping ; Zhuang, Huafeng ; Wu, Jingying ; Chen, Xiaofeng ; Wang, Weichun ; Wang, Yaoguo ; Chen, Youfang ; Wang, Shengnan ; Chen, Chunnuan

Sarcopenia has been recognized as an emerging complication of type 2 diabetes mellitus (T2DM). Currently, the pathogenesis of T2DM-related sarcopenia remains unclear. The aim of this study was to investigate the molecular mechanisms and potential therapeutic targets for T2DM-related sarcopenia. In this study, a T2DM-related sarcopenia mouse model was established using db/db mice. Proteins extracted from the gastrocnemius muscles of db/db mice and littermate control db/m mice were analyzed by a 4D label-free quantitative proteomics approach. A total of 131 upregulated and 68 downregulated proteins were identified as differentially expressed proteins (DEPs). Bioinformatics analysis revealed that DEPs were significantly enriched in lipid metabolism. Protein-protein interaction network analysis revealed that six hub proteins, including ACOX1, CPT2, ECI2, ACADVL, ACADL, and ECH1, were involved in the fatty acid oxidation. The hub protein-transcription factor-miRNA network was also constructed using the NetworkAnalyst tool. Finally, the hub proteins were validated by Western blotting and immunohistochemistry and further confirmed to be significantly negatively correlated with muscle mass and grip strength. Our study suggested that lipid metabolism, especially excessive fatty acid oxidation, may be a crucial contributor to the progression of T2DM-related sarcopenia and a common cause of the inter-relationship between T2DM and sarcopenia. Targeting lipid metabolism may be a promising therapeutic strategy for T2DM-related sarcopenia.

2024-08-01·Environment International

Arsenic exposure at environmentally relevant levels induced metabolic toxicity in development mice: Mechanistic insights from integrated transcriptome and metabolome

Article

作者: Liu, Qianying ; Li, Weiya ; Li, Peiwen ; Ma, Jinglan ; Liang, Sen ; Liu, Lu ; Zhang, Jiazhen ; Liu, Yuenan ; He, Meian

Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In this study, we used a mouse model to evaluate the health impacts and metabolic toxicity of arsenic exposure in drinking water at environmentally relevant levels (0.25 and 1.0 ppm). Our results indicated that arsenic damaged intestinal barrier and induced arsenic accumulation, oxidative stress, and pathological changes in the liver and illum. Interestingly, arsenic increased the hepatic triglyceride (TG) and total cholesterol (TC), while reduced serum TG and TC levels. The liver transcriptome found that arsenic exposure caused transcriptome perturbation and promoted hepatic lipid accumulation by regulating the exogenous fatty acids degradation and apolipoproteins related genes. The serum metabolomics identified 74 and 88 differential metabolites in 0.25 and 1.0 ppm, respectively. The KEGG disease and subcellular location analysis indicated that arsenic induced liver and intestinal diseases, and the mitochondrion might be the target organelle for arsenic-induced toxicity. Co-enrichment of transcriptome and metabolome identified 24 metabolites and 9 genes as metabolic toxicity biomarkers. Moreover, 40 male (20 nonalcoholic fatty liver disease (NAFLD) cases and 20 healthy controls) was further selected to validate our findings. Importantly, the significantly changed L-palmitoylcarnitine, 3-hydroxybutyric acid, 2-hydroxycaproic acid and 6 genes of Hadha, Acadl, Aldh3a2, Cpt1a, Cpt2, and Acox1 were found in the NAFLD cases. The results from integrated multi-omics and chemical-protein network analysis indicated that L-palmitoylcarnitine played a critical role in metabolic toxicity by regulating mitochondrial fatty acids β-oxidation genes (Cpt1a, Cpt2). In conclusion, these findings provided new clues for the metabolic toxicity of arsenic exposure at environmentally relevant levels, which involved in the late-life NAFLD development. Our results also contribute to understanding the human responses and phenotypic changes to this hazardous material exposure in the environment.

项与 ACADL 相关的新闻（医药）

2023-02-10

·生物探索

帕金森治疗有望！科学家在小鼠四肢中发现“超快”肌肉纤维

帕金森是一种慢性进行性神经变性疾病，基底节多巴胺缺乏导致帕金森典型的运动症状，即运动迟缓、震颤、强直和后来的姿势不稳。帕金森的发病率和患病率随年龄增长而增加，65岁以上人群中1%患有该病，且男性发病率是女性的2倍[1]。随着人口老龄化日趋严重，与年龄有关的疾病也日益受到关注。帕金森病例将从2015年的700万增加到2040年的1300万，意味着潜在的“大流行”，将会给社会和家庭带来巨大的负担。随着对帕金森发病机制了解的深入，研究人员提出了某些神经保护策略，可能在早期有利于影响疾病进展，但结果并不尽如人意。了解人体肌肉构成是改善神经肌肉疾病再生医学的关键一步，或许未来可能会为帕金森带来全新的治疗选择。但是很难量化肌肉变化的各个方面，包括基本细节，比如肌肉的哪些部位存在哪些纤维。如今，有科学家找到了识别这些纤维的方法。在动物中，有种“超快”肌肉可以像闪电侠那样快速移动，中科院动物和北京干细胞与再生医学研究所的科学家们首次在小鼠腿上发现了一种新的超快2B型肌纤维亚型，为未来打破正常人类手臂和腿部运动的物理速度限制带来了希望，或许将来可以用于帕金森等疾病的治疗。相关研究成果以“Spatial metabolomics reveals skeletal myofiber subtypes”为题，发表在Science Advances上。图1 研究成果（图源：[2]）肌肉由慢肌纤维和快肌纤维组成，慢肌纤维产生较小的肌肉收缩，更耐疲劳，而快肌纤维在较短的爆发中产生较大的收缩。有研究表明，重复运动会导致肌纤维类型发生转换，科学家们据此推测如果使用正确的技术，或许可以发现中间类型，模糊慢肌纤维和快肌纤维之间的界限。在这项研究中，研究人员结合质谱成像（MSI）和液相色谱质谱（LC-MS）的优势，对慢肌纤维和快肌纤维进行高空间分辨率代谢组学分析。骨骼肌由四种不同代谢特征的肌纤维亚型组成，由于肌肉结构较为简单、肌纤维的代谢异质性、单个肌纤维细胞的大小足以提供超过检测极限的代谢物为代谢组学分析提供了丰富的信息，因此其可以作为高空间分辨率代谢组学的理想模型。研究人员通过基于LC-MS的代谢组学分析在交叉验证后展示了慢肌和快肌肌纤维的代谢组学分析，MSI和LC-MS相结合，产生了更可靠的空间代谢组学结果。此外，通过小鼠纵向肌肉冷冻切片获得了高空间分辨率肌纤维MS图像，从而增加了每个肌纤维的横截面积，进而增加了离子丰度。利用技术优势，研究人员成功表征了肌纤维亚型的代谢特征，并在小鼠腿部肌肉内发现了一种罕见的新肌纤维亚型（2B mitohigh肌纤维）。图2 空间转录组学显示2B mitohigh肌纤维具有EOM的特性（图源：[2]）为了了解2B mitohigh肌纤维的特性，研究人员使用PCA可视化了其转录组基因表达，发现其富含Myh13、Myh8、Chrna2、 Acadl、 Ldhb等、肌动蛋白、神经肌肉及代谢相关基因，这些特征与眼外肌（EOM）类似。EOM通过代谢、收缩和结构蛋白的表达来实现视觉系统精确定位和快速跟踪等复杂的高度特化运动，具有抗疲劳且超快收缩的特性。研究人员对此进行进一步确认，发现2B mitohigh肌纤维与EOM的抗疲劳代谢特性一致。综上，通过该项研究，利用MSI和LC-MS相结合的方式，产生了可靠的空间代谢组学结果。经过分析，研究人员发现了一种类似EOM的超快肌肉纤维——2B mitohigh肌纤维。同时，也为利用高分辨率空间代谢组学与空间转录组学相结合的方式，去发现更多肌纤维和其他细胞类型的代谢亚型。肌纤维的代谢组学分析将提高我们对所有肌纤维亚型及其与运动表现、运动、肌肉减少症、恶病质、肌肉萎缩和肌肉相关代谢疾病之间关系的分子理解，进而有可能为基本生物过程和疾病状态的代谢调节提供重要的见解，或许有一天，可以为帕金森的治疗带来崭新的希望。责编|木子久排版|文竞择End参考资料： [1]张辉,王运良.帕金森病的发病机制及治疗进展[J].中国实用神经疾病杂志,2021,24(15):1371-1380.[2]Luo L, Ma W, Liang K, et al. Spatial metabolomics reveals skeletal myofiber subtypes. Sci Adv. 2023 Feb 3;9(5):eadd0455. doi: 10.1126/sciadv.add0455. Epub 2023 Feb 3. PMID: 36735792. 本文系生物探索原创，欢迎个人转发分享。其他任何媒体、网站如需转载，须在正文前注明来源生物探索。往期精选围观 ‍XY一定是男性吗？NO，可以是女性且能生子，Y染色体还可以来自妈妈！热文打一针即可有效治疗阿尔茨海默症！早期数据表明AC Immune阿尔茨海默症疫苗可引起反应热文新药王登顶！K药一年卖了超1400亿元！默沙东2022年财报出炉热文抑郁症的根源并不简单，抗抑郁药原方向可能有错热文与人类相似「一夫一妻制」啮齿动物不需要“爱情激素”就能形成伴侣关系点击“阅读原文”，了解更多~

临床研究