Metabolic and Tissue-Specific Regulation of Acyl-CoA Metabolism

Jessica M. Ellis, Caitlyn E. Bowman, Michael J Wolfgang

Research output: Contribution to journalArticle

Abstract

Acyl-CoA formation initiates cellular fatty acid metabolism. Acyl-CoAs are generated by the ligation of a fatty acid to Coenzyme A mediated by a large family of acyl-CoA synthetases (ACS). Conversely, acyl-CoAs can be hydrolyzed by a family of acyl-CoA thioesterases (ACOT). Here, we have determined the transcriptional regulation of all ACS and ACOT enzymes across tissues and in response to metabolic perturbations. We find patterns of coordinated regulation within and between these gene families as well as distinct regulation occurring in a tissue- and physiologically-dependent manner. Due to observed changes in long-chain ACOT mRNA and protein abundance in liver and adipose tissue, we determined the consequence of increasing cytosolic long-chain thioesterase activity on fatty acid metabolism in these tissues by generating transgenic mice overexpressing a hyperactive mutant of Acot7 in the liver or adipose tissue. Doubling cytosolic acyl-CoA thioesterase activity failed to protect mice from diet-induced obesity, fatty liver or insulin resistance, however, overexpression of Acot7 in adipocytes rendered mice cold intolerant. Together, these data suggest distinct modes of regulation of the ACS and ACOT enzymes and that these enzymes act in a coordinated fashion to control fatty acid metabolism in a tissue-dependent manner.

Original languageEnglish (US)
Article numbere0116587
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 11 2015

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Acyl Coenzyme A
long-chain-fatty-acid-CoA ligase
Metabolism
fatty acid metabolism
Coenzyme A Ligases
Tissue
metabolism
Fatty Acids
Liver
adipose tissue
mice
enzymes
liver protein
coenzyme A
Adipose Tissue
fatty liver
Enzymes
adipocytes
insulin resistance
obesity

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Metabolic and Tissue-Specific Regulation of Acyl-CoA Metabolism. / Ellis, Jessica M.; Bowman, Caitlyn E.; Wolfgang, Michael J.

In: PLoS One, Vol. 10, No. 3, e0116587, 11.03.2015.

Research output: Contribution to journalArticle

Ellis, Jessica M. ; Bowman, Caitlyn E. ; Wolfgang, Michael J. / Metabolic and Tissue-Specific Regulation of Acyl-CoA Metabolism. In: PLoS One. 2015 ; Vol. 10, No. 3.
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