| 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)
|
|---|
| 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.
|
