Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity

Research output: Contribution to journalArticle

Abstract

Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7N-/-, revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7N-/- mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7N-/- mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity.

Original languageEnglish (US)
Pages (from-to)1869-1882
Number of pages14
JournalMolecular and cellular biology
Volume33
Issue number9
DOIs
StatePublished - May 1 2013

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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