Biological role of the endogenous GPC-producing pathway and its application to metabolic improvement
| Project/Area Number |
25670032
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
MURAKAMI Makoto 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 参事研究員 (60276607)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 酵素 / 脂質 / 生体分子 / 遺伝子 / 組織・細胞 / 遺伝子改変マウス / メタボローム / 病態 / 細胞・組織 |
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| Outline of Final Research Achievements |
Phospholipase A2s (PLA2s) hydrolyze the sn-2 position of phospholipids to generate fatty acids and lysophospholipids. PNPLA7, a member of the iPLA2 family, acts as a lysophospholipase, which catalyzes the conversion of lysophosphatidylcholine (LPC) to glycerophosphocholine (GPC). In this study, we analyzed PNPLA7-deficient mice to decipher the biological role of this particular lysophospholipase. We found that the hepatic choline-methionine metabolic pathway was markedly perturbed in PNPLA7-deficient mice, which displayed growth retardation, fatty liver-like vacuolation, reduction and browning of white adipose tissue, impairment of VLDL secretion, starvation-like responses such as increased serum FGF1 and ketone body levels, and early death. Our results highlight the biological importance of the lysophospholipase as a GPC-producing enzyme and that this pathway is crucial for proper maintenance of the hepatic choline-methionine cycle and thereby systemic metabolism.
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] Lysophosphatidylcholine acyltransferase 1 altered phospholipid composition and regulated hepatoma progression.2013
Author(s)
Morita Y, Sakaguchi T, Ikegami K, Goto-Inoue N, Hayasaka T, Hang VT, Tanaka H, Harada T, Shibasaki Y, Suzuki A, Fukumoto K, Inaba K, Murakami M, Setou M, Konno H.
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Journal Title
J Hepatol.
Volume: 29
Issue: 2
Pages: 292-299
DOI
Related Report
Peer Reviewed
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[Presentation] Glycerophosphochoine production by PNPLA7, a novel starvation-induced lysophospholipase, , is essential for hepatic choline homeostasis.2013
Author(s)
Hirabayashi, T., Mouri, M., Shimamura, T., Anjo, T., Yokoyama, K., Ikeda, K., and Murakami, M.
Organizer
FASEB Summer Research Conference on Lysophospholipids and Other Related Mediators.
Place of Presentation
ニセコ
Related Report
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