Biological role of the endogenous GPC-producing pathway and its application to metabolic improvement

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670032
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• 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)
• Project Period (FY): 2013-04-01 – 2015-03-31
• 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

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.

Free Research Field

代謝学