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Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism

文献类型：期刊论文

作者Omiecinski, Curtis J.4; Patterson, Andrew D.4; Smith, Philip B.1; Tian, Yuan1; Zhang, Limin2,4; Chen, Tao4; Coslo, Denise M.4; Chen, Fengming3,4
刊名JOURNAL OF PROTEOME RESEARCH
出版日期2019
卷号18期号:1页码:239-251
ISSN号1535-3893
关键词NR1I3 constitutive androstane receptor metabolomics energy metabolism
DOI10.1021/acs.jproteome.8b00566
英文摘要The constitutive androstane receptor (CAR; NR1I3) contributes important regulatory roles in biotransformation, xenobiotic transport function, energy metabolism and lipid homeostasis. In this investigation, global serum and liver tissue metabolomes were assessed analytically in wild type and CAR-null transgenic mice using NMR, GC-MS and UPLC-MS/MS-based metabolomics. Significantly, CAR activation increased serum levels of fatty acids, lactate, ketone bodies and tricarboxylic acid cycle products, whereas levels of phosphatidylcholine, sphingomyelin, amino acids and liver glucose were decreased following short-term activation of CAR. Mechanistically, quantitative mRNA analysis demonstrated significantly decreased expression of key gluconeogenic pathways, and increased expression of glucose utilization pathways, changes likely resulting from down-regulation of the hepatic glucose sensor and bidirectional transporter, Glut2. Short-term CAR activation also resulted in enhanced fatty acid synthesis and impaired beta-oxidation. In summary, CAR contributes an expansive role regulating energy metabolism, significantly impacting glucose and monocarboxylic acid utilization, fatty acid metabolism and lipid homeostasis, through receptor-mediated regulation of several genes in multiple associated pathways.
WOS关键词CONSTITUTIVE ANDROSTANE RECEPTOR ; PREGNANE-X-RECEPTOR ; NUCLEAR RECEPTORS ; CROSS-TALK ; PHOSPHATIDYLCHOLINE SYNTHESIS ; DRUG-METABOLISM ; ACTIVATION ; PATHWAY ; HOMEOSTASIS ; PXR
资助项目National Institute of General Medical Sciences[GM066411] ; NIH shared instrumentation program[1S10OD021750] ; United States Department of Agriculture[4607]
WOS研究方向Biochemistry & Molecular Biology
语种英语
出版者AMER CHEMICAL SOC
WOS记录号WOS:000455285900021
资助机构National Institute of General Medical Sciences ; National Institute of General Medical Sciences ; NIH shared instrumentation program ; NIH shared instrumentation program ; United States Department of Agriculture ; United States Department of Agriculture ; National Institute of General Medical Sciences ; National Institute of General Medical Sciences ; NIH shared instrumentation program ; NIH shared instrumentation program ; United States Department of Agriculture ; United States Department of Agriculture ; National Institute of General Medical Sciences ; National Institute of General Medical Sciences ; NIH shared instrumentation program ; NIH shared instrumentation program ; United States Department of Agriculture ; United States Department of Agriculture ; National Institute of General Medical Sciences ; National Institute of General Medical Sciences ; NIH shared instrumentation program ; NIH shared instrumentation program ; United States Department of Agriculture ; United States Department of Agriculture
源URL[http://ir.wipm.ac.cn/handle/112942/14109]  
专题中国科学院武汉物理与数学研究所
通讯作者Omiecinski, Curtis J.
作者单位1.Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA
2.Chinese Acad Sci, CAS Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan Inst Phys & Math, Wuhan 430070, Peoples R China
3.Penn State Milton S Hershey Med Ctr, Dept Pathol, Hershey, PA 17033 USA
4.Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA
推荐引用方式
GB/T 7714		 Omiecinski, Curtis J.,Patterson, Andrew D.,Smith, Philip B.,et al. Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism[J]. JOURNAL OF PROTEOME RESEARCH,2019,18(1):239-251.
APA Omiecinski, Curtis J..,Patterson, Andrew D..,Smith, Philip B..,Tian, Yuan.,Zhang, Limin.,...&Chen, Fengming.(2019).Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism.JOURNAL OF PROTEOME RESEARCH,18(1),239-251.
MLA Omiecinski, Curtis J.,et al."Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism".JOURNAL OF PROTEOME RESEARCH 18.1(2019):239-251.

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来源：武汉物理与数学研究所

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