FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes
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FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes Yoshiteru Kagawa 1 & Banlanjo Abdulaziz Umaru 1 & Hiroki Shima 2 & Ryo Ito 3 & Ryo Zama 1 & Ariful Islam 1 & Shin-ichiro Kanno 4 & Akira Yasui 4 & Shun Sato 5 & Kosuke Jozaki 5 & Subrata Kumar Shil 1 & Hirofumi Miyazaki 1 & Shuhei Kobayashi 1 & Yui Yamamoto 1 & Hiroshi Kogo 6 & Chie Shimamoto-Mitsuyama 7 & Akira Sugawara 3 & Norihiro Sugino 5 & Masayuki Kanamori 8 & Teiji Tominaga 8 & Takeo Yoshikawa 7 & Kohji Fukunaga 9 & Kazuhiko Igarashi 2 & Yuji Owada 1 Received: 27 April 2020 / Accepted: 7 August 2020 # The Author(s) 2020
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. Keywords Fatty acid–binding protein (FABP) . ATP-citrate lyase (ACLY) . Acetyl-CoA . Histone acetylation . Caveolin-1 . Astrocyte
Abbreviations ACC Acetyl-CoA carboxylase ACLY ATP-citrate lyase
ACSS2 ALA
Acyl-coenzyme A synthetase short-chain family member 2 α-Linolenic acid
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02057-3) contains supplementary material, which is available to authorized users. * Yoshiteru Kagawa [email protected] * Yuji Owada [email protected] 1
Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
2
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
3
Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
4
Division of Dynamic Proteome in Aging and Cancer, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai 980-8575, Japan
5
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube 755-0046, Japan
6
Department of Anatomy and Cell Biology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan
7
Laboratory for Molecular Psychiatry, RIKEN Center for Brain Science, Wako 351-0198, Japan
8
Department of Neurosurgery, Tohoku Universi
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