Loss of the lipid enzyme PNPLA7 impairs skeletal muscle and mitochondria in mice

In mice and cultured mouse myoblasts, researchers examined the role of PNPLA7 in phosphatidylcholine turnover and skeletal muscle health. Deleting Pnpla7 in myoblasts blocked the conversion of lysophosphatidylcholine to glycerophosphocholine and choline. In mice, both global and muscle-specific Pnpla7 deficiency caused thinner quadriceps muscle fibers and abnormal mitochondrial structure. These animals also exhibited reduced endurance capacity. With age, the deficient mice showed decreased expression of genes linked to mitochondrial function, fatty acid beta-oxidation, and slow-twitch fibers. Before these muscle defects appeared, the researchers detected shifts in phospholipid composition, including lower levels of docosahexaenoic acid-containing phosphatidylcholine and mitochondrial cardiolipin. The findings identify PNPLA7 as a critical checkpoint enzyme for muscle homeostasis.