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 Tominaga; Takeo Yoshikawa; Kohji Fukunaga; Kazuhiko Igarashi; Yuji Owada

doi:10.1007/s12035-020-02057-3

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 journal › Article

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 language	English
Journal	Molecular Neurobiology
DOIs	https://doi.org/10.1007/s12035-020-02057-3
Publication status	Accepted/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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Kagawa, Y., Umaru, B. A., Shima, H., Ito, R., Zama, R., Islam, A., Kanno, S. I., Yasui, A., Sato, S., Jozaki, K., Shil, S. K., Miyazaki, H., Kobayashi, S., Yamamoto, Y., Kogo, H., Shimamoto-Mitsuyama, C., Sugawara, A., Sugino, N., Kanamori, M., ... Owada, Y. (Accepted/In press). FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes. Molecular Neurobiology. https://doi.org/10.1007/s12035-020-02057-3

FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes. / Kagawa, Yoshiteru; Umaru, Banlanjo Abdulaziz; Shima, Hiroki; Ito, Ryo; Zama, Ryo; Islam, Ariful; Kanno, Shin ichiro; Yasui, Akira; Sato, Shun; Jozaki, Kosuke; Shil, Subrata Kumar; Miyazaki, Hirofumi ; Kobayashi, Shuhei; Yamamoto, Yui; Kogo, Hiroshi; Shimamoto-Mitsuyama, Chie; Sugawara, Akira; Sugino, Norihiro; Kanamori, Masayuki ; Tominaga, Teiji; Yoshikawa, Takeo; Fukunaga, Kohji ; Igarashi, Kazuhiko ; Owada, Yuji.

In: Molecular Neurobiology, 2020.

Research output: Contribution to journal › Article

Kagawa, Y, Umaru, BA, Shima, H, Ito, R, Zama, R, Islam, A, Kanno, SI, Yasui, A, Sato, S, Jozaki, K, Shil, SK, Miyazaki, H , Kobayashi, S, Yamamoto, Y, Kogo, H, Shimamoto-Mitsuyama, C, Sugawara, A, Sugino, N, Kanamori, M , Tominaga, T, Yoshikawa, T, Fukunaga, K , Igarashi, K & Owada, Y 2020, 'FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes', Molecular Neurobiology. https://doi.org/10.1007/s12035-020-02057-3

Kagawa, Yoshiteru ; Umaru, Banlanjo Abdulaziz ; Shima, Hiroki ; Ito, Ryo ; Zama, Ryo ; Islam, Ariful ; Kanno, Shin ichiro ; Yasui, Akira ; Sato, Shun ; Jozaki, Kosuke ; Shil, Subrata Kumar ; Miyazaki, Hirofumi ; Kobayashi, Shuhei ; Yamamoto, Yui ; Kogo, Hiroshi ; Shimamoto-Mitsuyama, Chie ; Sugawara, Akira ; Sugino, Norihiro ; Kanamori, Masayuki ; Tominaga, Teiji ; Yoshikawa, Takeo ; Fukunaga, Kohji ; Igarashi, Kazuhiko ; Owada, Yuji. / FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes. In: Molecular Neurobiology. 2020.

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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.",

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AU - Kagawa, Yoshiteru

AU - Umaru, Banlanjo Abdulaziz

AU - Shima, Hiroki

AU - Ito, Ryo

AU - Zama, Ryo

AU - Islam, Ariful

AU - Kanno, Shin ichiro

AU - Yasui, Akira

AU - Sato, Shun

AU - Jozaki, Kosuke

AU - Shil, Subrata Kumar

AU - Miyazaki, Hirofumi

AU - Kobayashi, Shuhei

AU - Yamamoto, Yui

AU - Kogo, Hiroshi

AU - Shimamoto-Mitsuyama, Chie

AU - Sugawara, Akira

AU - Sugino, Norihiro

AU - Kanamori, Masayuki

AU - Tominaga, Teiji

AU - Yoshikawa, Takeo

AU - Fukunaga, Kohji

AU - Igarashi, Kazuhiko

AU - Owada, Yuji

PY - 2020

Y1 - 2020

N2 - 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.

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