| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Choline, an essential nutrient, is supplied from the diet as well as via the liberation from its largest endogenous pool, phosphatidylcholine (PC), by the sequential action of phospholipase A (PLA), lysophospholipase, and glycerophosphodiesterase. Here we show that PNPLA7, a member of the PLA family, functions as a lysophospholipase responsible for the hepatic PC degradation machinery that provides glycerophosphocholine (GPC) and thereby choline in the liver. Pnpla7-/- mice showed a drastic reduction in hepatic choline metabolites, displaying growth retardation, short life span, hypoglycemia with mild ketosis, profound reduction in fat mass with “browning” of white adipocytes. and neurodegeneration. Moreover, we identified PNPLA8 as an upstream PLA subtype that supplies the substrate lysophosphocholine to PNPLA7. Our study reveals the PNPLA8-PNPLA7 axis as a critical component of the PC-catabolic pathway required for hepatic choline metabolism and systemic energy homeostasis.
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