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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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. Acyl-CoA-binding protein (ACBP) or diazepam-binding inhibitor is a secreted peptide acting centrally as a GABAA allosteric modulator. Using brain slices, cortical, and hypothalamic astrocyte cultures from ACBP KO mice, we demonstrate that ACBP mainly localizes in astrocytes and regulates unsaturated but not saturated long-chain fatty acids (LCFA) metabolism. In addition, ACBP deficiency alters FA metabolism-related genes and results in intracellular FA accumulation while affecting their release. Our results support a novel role for ACBP in brain lipid metabolism. FA, fatty acids; KO, knockout; PL, phospholipids; TAG, triacylglycerol.

OriginalsprogEngelsk
TidsskriftJournal of Neurochemistry
Vol/bind133
Udgave nummer2
Sider (fra-til)253-65
Antal sider13
ISSN0022-3042
DOI
StatusUdgivet - apr. 2015

Fingeraftryk

Diazepam Binding Inhibitor
Metabolism
Fatty Acids
Protein Deficiency
5-methoxy-methylindoleacetic acid
Astrocytes
Brain
Acyl Coenzyme A
Palmitates
Modulators
Genes

Citer dette

Bouyakdan, Khalil ; Taïb, Bouchra ; Budry, Lionel ; Zhao, Shangang ; Rodaros, Demetra ; Neess, Ditte ; Mandrup, Susanne ; Faergeman, Nils J ; Alquier, Thierry. / A novel role for central ACBP/DBI as a regulator of long-chain fatty acid metabolism in astrocytes. I: Journal of Neurochemistry. 2015 ; Bind 133, Nr. 2. s. 253-65.
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title = "A novel role for central ACBP/DBI as a regulator of long-chain fatty acid metabolism in astrocytes",
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. Acyl-CoA-binding protein (ACBP) or diazepam-binding inhibitor is a secreted peptide acting centrally as a GABAA allosteric modulator. Using brain slices, cortical, and hypothalamic astrocyte cultures from ACBP KO mice, we demonstrate that ACBP mainly localizes in astrocytes and regulates unsaturated but not saturated long-chain fatty acids (LCFA) metabolism. In addition, ACBP deficiency alters FA metabolism-related genes and results in intracellular FA accumulation while affecting their release. Our results support a novel role for ACBP in brain lipid metabolism. FA, fatty acids; KO, knockout; PL, phospholipids; TAG, triacylglycerol.",
author = "Khalil Bouyakdan and Bouchra Ta{\"i}b and Lionel Budry and Shangang Zhao and Demetra Rodaros and Ditte Neess and Susanne Mandrup and Faergeman, {Nils J} and Thierry Alquier",
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A novel role for central ACBP/DBI as a regulator of long-chain fatty acid metabolism in astrocytes. / Bouyakdan, Khalil; Taïb, Bouchra; Budry, Lionel; Zhao, Shangang; Rodaros, Demetra; Neess, Ditte; Mandrup, Susanne; Faergeman, Nils J; Alquier, Thierry.

I: Journal of Neurochemistry, Bind 133, Nr. 2, 04.2015, s. 253-65.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A novel role for central ACBP/DBI as a regulator of long-chain fatty acid metabolism in astrocytes

AU - Bouyakdan, Khalil

AU - Taïb, Bouchra

AU - Budry, Lionel

AU - Zhao, Shangang

AU - Rodaros, Demetra

AU - Neess, Ditte

AU - Mandrup, Susanne

AU - Faergeman, Nils J

AU - Alquier, Thierry

N1 - © 2015 International Society for Neurochemistry.

PY - 2015/4

Y1 - 2015/4

N2 - 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. Acyl-CoA-binding protein (ACBP) or diazepam-binding inhibitor is a secreted peptide acting centrally as a GABAA allosteric modulator. Using brain slices, cortical, and hypothalamic astrocyte cultures from ACBP KO mice, we demonstrate that ACBP mainly localizes in astrocytes and regulates unsaturated but not saturated long-chain fatty acids (LCFA) metabolism. In addition, ACBP deficiency alters FA metabolism-related genes and results in intracellular FA accumulation while affecting their release. Our results support a novel role for ACBP in brain lipid metabolism. FA, fatty acids; KO, knockout; PL, phospholipids; TAG, triacylglycerol.

AB - 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. Acyl-CoA-binding protein (ACBP) or diazepam-binding inhibitor is a secreted peptide acting centrally as a GABAA allosteric modulator. Using brain slices, cortical, and hypothalamic astrocyte cultures from ACBP KO mice, we demonstrate that ACBP mainly localizes in astrocytes and regulates unsaturated but not saturated long-chain fatty acids (LCFA) metabolism. In addition, ACBP deficiency alters FA metabolism-related genes and results in intracellular FA accumulation while affecting their release. Our results support a novel role for ACBP in brain lipid metabolism. FA, fatty acids; KO, knockout; PL, phospholipids; TAG, triacylglycerol.

U2 - 10.1111/jnc.13035

DO - 10.1111/jnc.13035

M3 - Journal article

C2 - 25598214

VL - 133

SP - 253

EP - 265

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -