The acyl-CoA binding protein is required for normal epidermal barrier function in mice

Abstract

This article is available online at http://www.jlr.org Supplementary key words stratum corneum • very long chain fatty acids • mono alkyl diacyl glycerol • transepidermal water loss • multiphoton excitation microscopy • lipid mass spectrometryThe acyl-CoA binding protein (ACBP)/diazepam binding inhibitor (DBI) (Entrez Gene ID: 13167) is a 10 kDa intracellular protein that specifi cally binds medium and long chain acyl-CoA esters (C 14 -C 22 ) with very high affi nity (K d ‫ف‬ 1-10 nM) ( 1, 2 ). The protein is expressed in all eukaryotic species and in all mammalian tissues investigated ( 3-5 ); however, expression levels differs markedly between different tissues and cell types examined, with particularly high levels in epithelial cell types and in cells with a high turn-over of fatty acids (FA) ( 6 ). Consistently with this, we have shown that the ACBP gene is activated by lipogenic transcription factors, such as the peroxisome proliferatoractivated receptor ␥ ( 7 ) and members of the sterol-regulatory element binding protein family ( 7-10 ). In vitro studies indicate that ACBP plays a role in transport of acyl-CoA esters and may deliver acyl-CoA esters to phospholipid

Current status and future perspectives: TSPO in steroid neuroendocrinology

“…As described previously, ACBP function is linked to lipid metabolism (Mandrup et al 1993, Gaigg et al 2001. These observations were confirmed in ACBP-knockout mice that indicate no role in steroid synthesis (Neess et al 2011, Bloksgaard et al 2012. Moreover, studies by independent groups could not confirm the TSPO-DBI interaction (Bogan et al 2007).…”

“…Loss of ACBP in these nm1054 mice was linked to fatty acid metabolism abnormalities in skin and hair ). The subsequent generation of viable Acbp-knockout mice (Acbp −/− ) displayed delayed metabolic adaptation to weaning (Neess et al 2011), and a phenotype of fatty acid metabolic abnormalities in skin and hair similar to nm1054 mutation (Bloksgaard et al 2012, Neess et al 2013. There was no phenotypic evidence that indicated defects in steroid hormone production in these Acbp −/− mice.…”

Compromised epidermal barrier stimulates Harderian gland activity and hypertrophy in ACBP−/− mice

“…The fatty acids used for synthesis of MADAG originate primarily from de novo fatty acid synthesis in the gland ( 34,35 ). In vivo pulselabeling with 14 C-acetic acid showed that de novo synthesis of MADAG in Harderian glands is signifi cantly higher in ACBP Ϫ / Ϫ mice compared with ACBP +/+ mice ( Fig. 3B ).…”

“…Band intensities were determined by densitometry. The visualization of 14 C-labeled lipids and the total lipids was carried out as previously described ( 13 ). of triacylglycerol and cholesteryl esters ( 13 ).…”

“…Immediately thereafter, similar-sized explants (approximately half a gland) were incubated for 2 h in Krebs ringer buffer with 1% fatty acid-free BSA containing 0.5 µCi/ml 14 C-acetic acid ( [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C] acetic acid, sodium salt; Amersham Biosciences) at 37°C. Explants were removed and washed, and the weight was determined.…”