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  N-acetylaspartate catabolism determines cytosolic acetyl-CoA levels and histone acetylation in brown adipocytes

Prokesch, A., Pelzmann, H. J., Pessentheiner, A. R., Huber, K., Madreiter-Sokolowski, C. T., Drougard, A., et al. (2016). N-acetylaspartate catabolism determines cytosolic acetyl-CoA levels and histone acetylation in brown adipocytes. Scientific Reports, 6, 23723. doi:10.1038/srep23723.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002C-B0D7-7 Version Permalink: https://hdl.handle.net/21.11116/0000-0008-A5E0-0
Genre: Journal Article

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https://www.nature.com/articles/srep23723 (Publisher version)
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 Creators:
Prokesch, A.1, Author
Pelzmann, H. J.1, Author
Pessentheiner, A. R.1, Author
Huber, K.1, Author
Madreiter-Sokolowski, C. T.1, Author
Drougard, A.2, Author
Schittmayer, M.1, Author
Kolb, D.1, Author
Magnes, C.1, Author
Trausinger, G.1, Author
Graier, W. F.1, Author
Birner-Gruenberger, R.1, Author
Pospisilik, J. A.2, Author
Bogner-Strauss, & J. G.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

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 Abstract: Histone acetylation depends on the abundance of nucleo-cytoplasmic acetyl-CoA. Here, we present a novel route for cytoplasmic acetyl-CoA production in brown adipocytes. N-acetylaspartate (NAA) is a highly abundant brain metabolite catabolized by aspartoacylase yielding aspartate and acetate. The latter can be further used for acetyl-CoA production. Prior to this work, the presence of NAA has not been described in adipocytes. Here, we show that accumulation of NAA decreases the brown adipocyte phenotype. We increased intracellular NAA concentrations in brown adipocytes via media supplementation or knock-down of aspartoacylase and measured reduced lipolysis, thermogenic gene expression, and oxygen consumption. Combinations of approaches to increase intracellular NAA levels showed additive effects on lipolysis and gene repression, nearly abolishing the expression of Ucp1, Cidea, Prdm16, and Ppara. Transcriptome analyses of aspartoacylase knock-down cells indicate deficiencies in acetyl-CoA and lipid metabolism. Concordantly, cytoplasmic acetyl-CoA levels and global histone H3 acetylation were decreased. Further, activating histone marks (H3K27ac and H3K9ac) in promoters/enhancers of brown marker genes showed reduced acetylation status. Taken together, we present a novel route for cytoplasmic acetyl-CoA production in brown adipocytes. Thereby, we mechanistically connect the NAA pathway to the epigenomic regulation of gene expression, modulating the phenotype of brown adipocytes.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/srep23723
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Title: Scientific Reports
  Abbreviation : Sci. Rep.
Source Genre: Journal
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Publ. Info: London, UK : Nature Publishing Group
Pages: - Volume / Issue: 6 Sequence Number: - Start / End Page: 23723 Identifier: ISSN: 2045-2322
CoNE: https://pure.mpg.de/cone/journals/resource/2045-2322