1 Citation (Scopus)

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)239-251
Number of pages13
JournalJournal of Proteome Research
Volume18
Issue number1
DOIs
StatePublished - Jan 4 2019

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Metabolomics
Energy Metabolism
Fatty Acids
Chemical activation
Glucose
Liver
Glucose sensors
Lipids
Ketone Bodies
Homeostasis
Sphingomyelins
Xenobiotics
Phosphatidylcholines
Metabolism
Citric Acid Cycle
Metabolome
Lactic Acid
Biotransformation
Genes
Serum

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Chemistry(all)

Cite this

Chen, Fengming ; Coslo, Denise M. ; Chen, Tao ; Zhang, Limin ; Tian, Yuan ; Smith, Philip B. ; Patterson, Andrew David ; Omiecinski, Curtis John. / Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism. In: Journal of Proteome Research. 2019 ; Vol. 18, No. 1. pp. 239-251.
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abstract = "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 β-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.",
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Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism. / Chen, Fengming; Coslo, Denise M.; Chen, Tao; Zhang, Limin; Tian, Yuan; Smith, Philip B.; Patterson, Andrew David; Omiecinski, Curtis John.

In: Journal of Proteome Research, Vol. 18, No. 1, 04.01.2019, p. 239-251.

Research output: Contribution to journalArticle

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T1 - Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism

AU - Chen, Fengming

AU - Coslo, Denise M.

AU - Chen, Tao

AU - Zhang, Limin

AU - Tian, Yuan

AU - Smith, Philip B.

AU - Patterson, Andrew David

AU - Omiecinski, Curtis John

PY - 2019/1/4

Y1 - 2019/1/4

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