Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver.

Published

Journal Article

Acyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed in highly oxi-dative tissues and is poised to modulate mitochondrial FA oxidation (FAO), yet its biological role is unknown. Using a model of adenoviral Acot2 overexpression in mouse liver (Ad-Acot2), we show that Acot2 increases the utilization of FA substrate during the daytime in ad libitum-fed mice, but the nighttime switch to carbohydrate oxidation is similar to control mice. In further support of elevated FAO in Acot2 liver, daytime serum ketones were higher in Ad-Acot2 mice, and overnight fasting led to minimal hepatic steatosis as compared with control mice. In liver mitochondria from Ad-Acot2 mice, phosphorylating O₂ consumption was higher with lipid substrate, but not with nonlipid substrate. This increase depended on whether FA could be activated on the outer mitochondrial membrane, suggesting that the FA released by Acot2 could be effluxed from mitochondria then taken back up again for oxidation. This circuit would prevent the build-up of inhibitory long-chain fatty acyl-CoA esters. Altogether, our findings indicate that Acot2 can enhance FAO, possibly by mitigating the accumulation of FAO intermediates within the mitochondrial matrix.

Full Text

Duke Authors

Cited Authors

  • Moffat, C; Bhatia, L; Nguyen, T; Lynch, P; Wang, M; Wang, D; Ilkayeva, OR; Han, X; Hirschey, MD; Claypool, SM; Seifert, EL

Published Date

  • December 2014

Published In

Volume / Issue

  • 55 / 12

Start / End Page

  • 2458 - 2470

PubMed ID

  • 25114170

Pubmed Central ID

  • 25114170

Electronic International Standard Serial Number (EISSN)

  • 1539-7262

International Standard Serial Number (ISSN)

  • 0022-2275

Digital Object Identifier (DOI)

  • 10.1194/jlr.M046961

Language

  • eng