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 2013

Fingerprint

Acyl Coenzyme A
Fatty Acids
Lipid Metabolism
Neurons
Metabolomics
Dyslipidemias
Neurodegenerative Diseases
Energy Metabolism
Nervous System
Liver
Brain

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity. / Ellis, Jessica M.; Wong, Guang William; Wolfgang, Michael J.

In: Molecular and Cellular Biology, Vol. 33, No. 9, 05.2013, p. 1869-1882.

Research output: Contribution to journalArticle

@article{d42e98ded13b4920a12a958c675efe5a,
title = "Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity",
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.",
author = "Ellis, {Jessica M.} and Wong, {Guang William} and Wolfgang, {Michael J}",
year = "2013",
month = "5",
doi = "10.1128/MCB.01548-12",
language = "English (US)",
volume = "33",
pages = "1869--1882",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "9",

}

TY - JOUR

T1 - Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity

AU - Ellis, Jessica M.

AU - Wong, Guang William

AU - Wolfgang, Michael J

PY - 2013/5

Y1 - 2013/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84876472084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876472084&partnerID=8YFLogxK

U2 - 10.1128/MCB.01548-12

DO - 10.1128/MCB.01548-12

M3 - Article

VL - 33

SP - 1869

EP - 1882

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 9

ER -