Skip to main content
Journal cover image

Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism.

Publication ,  Journal Article
Chen, F; Coslo, DM; Chen, T; Zhang, L; Tian, Y; Smith, PB; Patterson, AD; Omiecinski, CJ
Published in: J Proteome Res
January 4, 2019

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

January 4, 2019

Volume

18

Issue

1

Start / End Page

239 / 251

Location

United States

Related Subject Headings

  • Receptors, Cytoplasmic and Nuclear
  • Mice, Transgenic
  • Mice
  • Metabolomics
  • Liver
  • Lipid Metabolism
  • Glucose
  • Gluconeogenesis
  • Fatty Acids
  • Energy Metabolism
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chen, F., Coslo, D. M., Chen, T., Zhang, L., Tian, Y., Smith, P. B., … Omiecinski, C. J. (2019). Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism. J Proteome Res, 18(1), 239–251. https://doi.org/10.1021/acs.jproteome.8b00566
Chen, Fengming, Denise M. Coslo, Tao Chen, Limin Zhang, Yuan Tian, Philip B. Smith, Andrew D. Patterson, and Curtis J. Omiecinski. “Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism.J Proteome Res 18, no. 1 (January 4, 2019): 239–51. https://doi.org/10.1021/acs.jproteome.8b00566.
Chen F, Coslo DM, Chen T, Zhang L, Tian Y, Smith PB, et al. Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism. J Proteome Res. 2019 Jan 4;18(1):239–51.
Chen, Fengming, et al. “Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism.J Proteome Res, vol. 18, no. 1, Jan. 2019, pp. 239–51. Pubmed, doi:10.1021/acs.jproteome.8b00566.
Chen F, Coslo DM, Chen T, Zhang L, Tian Y, Smith PB, Patterson AD, Omiecinski CJ. Metabolomic Approaches Reveal the Role of CAR in Energy Metabolism. J Proteome Res. 2019 Jan 4;18(1):239–251.
Journal cover image

Published In

J Proteome Res

DOI

EISSN

1535-3907

Publication Date

January 4, 2019

Volume

18

Issue

1

Start / End Page

239 / 251

Location

United States

Related Subject Headings

  • Receptors, Cytoplasmic and Nuclear
  • Mice, Transgenic
  • Mice
  • Metabolomics
  • Liver
  • Lipid Metabolism
  • Glucose
  • Gluconeogenesis
  • Fatty Acids
  • Energy Metabolism