FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes

Yoshiteru Kagawa, Banlanjo Abdulaziz Umaru, Hiroki Shima, Ryo Ito, Ryo Zama, Ariful Islam, Shin ichiro Kanno, Akira Yasui, Shun Sato, Kosuke Jozaki, Subrata Kumar Shil, Hirofumi Miyazaki, Shuhei Kobayashi, Yui Yamamoto, Hiroshi Kogo, Chie Shimamoto-Mitsuyama, Akira Sugawara, Norihiro Sugino, Masayuki Kanamori, Teiji TominagaTakeo Yoshikawa, Kohji Fukunaga, Kazuhiko Igarashi, Yuji Owada

Research output: Contribution to journalArticle

Abstract

Fatty acid binding protein 7 (FABP7) is an intracellular fatty acid chaperon that is highly expressed in astrocytes, oligodendrocyte-precursor cells, and malignant glioma. Previously, we reported that FABP7 regulates the response to extracellular stimuli by controlling the expression of caveolin-1, an important component of lipid raft. Here, we explored the detailed mechanisms underlying FABP7 regulation of caveolin-1 expression using primary cultured FABP7-KO astrocytes as a model of loss of function and NIH-3T3 cells as a model of gain of function. We discovered that FABP7 interacts with ATP-citrate lyase (ACLY) and is important for acetyl-CoA metabolism in the nucleus. This interaction leads to epigenetic regulation of several genes, including caveolin-1. Our novel findings suggest that FABP7-ACLY modulation of nuclear acetyl-CoA has more influence on histone acetylation than cytoplasmic acetyl-CoA. The changes to histone structure may modify caveolae-related cell activity in astrocytes and tumors, including malignant glioma.

Original languageEnglish
JournalMolecular Neurobiology
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • ATP-citrate lyase (ACLY)
  • Acetyl-CoA
  • Astrocyte
  • Caveolin-1
  • Fatty acid–binding protein (FABP)
  • Histone acetylation

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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