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Carboxylesterases are uniquely expressed among tissues and regulated by nuclear hormone receptors in the mouse

Ryan D Jones1, Anna M Taylor, Ernest Y Tong

  • 1Departments of Physiology, UT Southwestern Medical Center, Dallas, TX 75390-9077, USA.

Drug Metabolism and Disposition: the Biological Fate of Chemicals
|September 27, 2012
PubMed

Insights

Carboxylesterases (CES) are enzymes with diverse roles. This study maps mouse CES gene expression across tissues, revealing unique patterns suggesting specialized functions in lipid metabolism and detoxification.

Area of Science:

  • Biochemistry
  • Genomics
  • Pharmacology

Background:

  • Carboxylesterases (CES) are proteins catalyzing neutral lipid hydrolysis.
  • CES enzymes are involved in xenobiotic clearance, drug activation, and potentially lipid metabolism.
  • Mouse genomes contain 20 Ces genes, but their tissue-specific expression is poorly understood due to high sequence similarity.

Purpose of the Study:

  • To comprehensively analyze the tissue distribution of mouse carboxylesterase (Ces) mRNA expression.
  • To investigate the differential regulation of Ces gene expression in response to nuclear hormone receptor activation.
  • To examine Ces gene expression shifts in disease models, including inflammation and fatty liver disease.

Main Methods:

  • Quantitative analysis of mouse Ces mRNA levels across various tissues.
  • Assessment of Ces gene expression changes following treatment with lipid- and xenobiotic-sensing nuclear hormone receptor activators.
  • Evaluation of Ces gene expression in peritoneal macrophages after lipopolysaccharide stimulation and in a high-fat diet-induced steatotic liver model.

Main Results:

  • Mouse Ces family 1 shows high liver expression, and family 2 shows high intestinal expression.
  • Many other Ces genes exhibit unique and widespread tissue distribution patterns based on mRNA levels.
  • Differential regulation of Ces genes was observed upon nuclear hormone receptor activation, and expression shifted in response to inflammatory and steatotic conditions.

Conclusions:

  • Each mouse Ces gene possesses a distinct tissue expression profile.
  • These unique expression patterns suggest specialized roles for specific CES enzymes in tissue-specific lipid metabolism and xenobiotic clearance.
  • The findings provide a foundation for understanding the diverse physiological and pathological functions of carboxylesterases.

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