A novel role for central ACBP/DBI as a regulator of long-chain fatty acid metabolism in astrocytes

Khalil Bouyakdan, Bouchra Taïb, Lionel Budry, Shangang Zhao, Demetra Rodaros, Ditte Neess, Susanne Mandrup, Nils J. Faergeman, Thierry Alquier

Research output: Contribution to journalArticlepeer-review

Abstract

Acyl-CoA-binding protein (ACBP) is a ubiquitously expressed protein that binds intracellular acyl-CoA esters. Several studies have suggested that ACBP acts as an acyl-CoA pool former and regulates long-chain fatty acids (LCFA) metabolism in peripheral tissues. In the brain, ACBP is known as Diazepam-Binding Inhibitor, a secreted peptide acting as an allosteric modulator of the GABAA receptor. However, its role in central LCFA metabolism remains unknown. In the present study, we investigated ACBP cellular expression, ACBP regulation of LCFA intracellular metabolism, FA profile, and FA metabolism-related gene expression using ACBP-deficient and control mice. ACBP was mainly found in astrocytes with high expression levels in the mediobasal hypothalamus. We demonstrate that ACBP deficiency alters the central LCFA-CoA profile and impairs unsaturated (oleate, linolenate) but not saturated (palmitate, stearate) LCFA metabolic fluxes in hypothalamic slices and astrocyte cultures. In addition, lack of ACBP differently affects the expression of genes involved in FA metabolism in cortical versus hypothalamic astrocytes. Finally, ACBP deficiency increases FA content and impairs their release in response to palmitate in hypothalamic astrocytes. Collectively, these findings reveal for the first time that central ACBP acts as a regulator of LCFA intracellular metabolism in astrocytes.

Original languageEnglish (US)
Pages (from-to)253-265
Number of pages13
JournalJournal of Neurochemistry
Volume133
Issue number2
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Keywords

  • acyl-CoA
  • astrocytes
  • endozepines
  • fatty acid esterification
  • fatty acid oxidation
  • hypothalamus

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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