Elucidatiaon of the role of KAT2A in the regualtion of energy metabolism
| Project/Area Number |
15H04851
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
MATSUMOTO MICHIHIRO 国立研究開発法人国立国際医療研究センター, 研究所 糖尿病研究センター 分子代謝制御研究部, 部長 (90467663)
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| Co-Investigator(Renkei-kenkyūsha) |
KIDO Yoshiaki 神戸大学, 大学院・保健学研究科, 教授 (10335440)
INOUE Hiroshi 金沢大学, 新学術創成研究機構, 教授 (50397832)
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| Research Collaborator |
SAKAI Mashito
MITSUSHIMA Masaru
NAGANUMA Takao
YANO Hiroyuki
YAGI Takashi
MATSUKAWA Toshiya
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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| Keywords | 代謝調節 / 転写 / 酵素 / エピゲノム修飾 / 肥満 / 糖尿病 / 肝臓 / 脂肪組織 / 遺伝子転写 / エピジェネティクス / 遺伝子 / 発現制御 / 代謝 |
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| Outline of Final Research Achievements |
The role of KAT2A in hepatocytes was investigated in the regulation of fasting metabolism using loss-of-function approaches in vivo and in vitro. In the fasted state, hepatic KAT2A formed a signalling module with transcriptional coregulator CITED2 and PKA promoted transcription of fasting response genes, and thereby adapted to fasting. Mechanistically, KAT2A was phosphorylated by PKA within the module, switched its substrate from transcriptional coactivator PGC-1α to histone H3, and thereby promoted activation of this coactivator and epigenomic changes in the promoter, resulting in activation of such gene transcription. These results suggest that KAT2A is a cAMP-responsible acetyltransferase that is critical to integrate fasting metabolic response in hepatocytes.
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Report
(4 results)
Research Products
(48 results)
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[Journal Article] Circadian clock regulates hepatic polyploidy by modulating Mkp1-Erk1/2 signaling pathway.2017
Author(s)
Chao HW, Doi M, Fustin JM, Chen H, Murase K, Maeda Y, Hayashi H, Tanaka R, Sugawa M, Mizukuchi N, Yamaguchi Y, Yasunaga J, Matsuoka M, Sakai M, Matsumoto M, Hamada S, and Okamura H
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Journal Title
Nature Commun.
Volume: 8
Issue: 1
Pages: 2238-2238
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Proteomic analysis of serum biomarkers for prediabetes using the Long-Evans Agouti rat, a spontaneous animal model of type 2 diabetes mellitus.2017
Author(s)
Takahashi E, Unoki-Kubota H, Shimizu Y, Okamura T, Iwata W, Kajio H, Yamamoto-Honda R, Shiga T, Yamashita S, Tobe K, Okumura A, Matsumoto M, Yasuda K, Noda M, Kaburagi Y.
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Journal Title
J Diabetes Investig.
Volume: 印刷中
Issue: 5
Pages: 661-671
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dietary Mung Bean Protein Reduces Hepatic Steatosis, Fibrosis, and Inflammation in Male Mice with Diet-Induced, Nonalcoholic Fatty Liver Disease.2017
Author(s)
Watanabe H, Inaba Y, Kimura K, Asahara SI, Kido Y, Matsumoto M, Motoyama T, Tachibana N, Kaneko S, Kohno M, Inoue H*.
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Journal Title
J Nutr.
Volume: 147
Issue: 1
Pages: 52-60
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] The GCN5-CITED2-PKA signalling module controls hepatic glucose metabolism through a cAMP-induced substrate switch.2016
Author(s)
Sakai M, Tujimura-Hayakawa T, Yagi T, Yano H, Mitsushima M, Unoki-Kubota H, Kaburagi Y, Inoue H, Kido Y, Kasuga M, Matsumoto M.
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Journal Title
Nat Commun.
Volume: 7
Issue: 1
Pages: 13147-13147
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Karigane D, Kobayashi H, Morikawa T, Ootomo Y, Sakai M, Nagamatsu G, Kubota Y, Goda N, Matsumoto M, Nishimura EK, Soga T, Otsu K, Suematsu M, Okamoto S, Suda T, Takubo K.2016
Author(s)
Karigane D, Kobayashi H, Morikawa T, Ootomo Y, Sakai M, Nagamatsu G, Kubota Y, Goda N, Matsumoto M, Nishimura EK, Soga T, Otsu K, Suematsu M, Okamoto S, Suda T, Takubo K.
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Journal Title
Cell Stem Cell
Volume: 19
Issue: 2
Pages: 192-204
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Centra insulin-action activates Kupffer cells by suppressing hepatic vagal activation through nicotinic alpha 7 acetylcholine receptor.2016
Author(s)
Kimura K, Tanida M, Nagata N, Inaba Y, Watanabe H, Nagashimada M, Ota T, Asahara S, Kido Y, Matsumoto M, Toshinai K, Nakazato M, Shibamoto T, Kaneko S, Kasuga M, Inoue H
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Journal Title
Cell reports
Volume: 14
Issue: 10
Pages: 2362-2374
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hepatocyte β-Klotho regulates lipid homeostasis but not body weight in mice.2016
Author(s)
Kobayashi K, Tanaka T, Okada S, Morimoto Y, Matsumura S, Manio MC, Inoue K, Kimura K, Yagi T, Saito Y, Fushiki T, Inoue H, Matsumoto M, Nabeshima Y.
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Journal Title
FASEB J.
Volume: 30
Issue: 2
Pages: 849-62
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Paternal allelic mutation at the Kcnq1 locus reduces pancreatic β cell mass via epigenetic modification of Cdkn1c.2015
Author(s)
Asahara S, Etoh H, Inoue H, Teruyama K, Shibutani Y, Ihara Y, Kawada Y, Bartolome A, Hashimoto N, Matsuda T, Koyanagi-Kimura M, Kanno A, Hirota Y, Hosooka T, Nagashima K, Nishimura W, Inoue H, Matsumoto M, Higgins MJ, Yasuda K, Inagaki N, Seino S, Kasuga M, Kido Y.
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Journal Title
Proceedings of the National Acaddemy of Scienceof the United States of America
Volume: 112(27)
Issue: 27
Pages: 8332-8337
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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