The concentration of phosphatidylethanolamine in mitochondria can modulate ATP production and Glucose Metabolism in Mice

Abstract

Phosphatidylethanolamine (PE) N-methyltransferase (PEMT) catalyzes the synthesis of phosphatidylcholine (PC) in the liver. Mice lacking PEMT are protected against diet-induced obesity and insulin resistance. We investigated the role of PEMT in hepatic carbohydrate metabolism in chow-fed mice. A pyruvate tolerance test revealed that PEMT deficiency greatly attenuated gluco-neogenesis. The reduction in glucose production was specific for pyruvate; glucose production from glycerol was unaffected. Mitochondrial PC levels were lower and PE levels were higher in livers from Pemt-/- compared with Pemt+/+ mice, resulting in a 33% reduction of the PC-to-PE ratio. Mitochondria from Pemt-/- mice were also smaller and more elongated. Activities of cytochrome c oxidase and succinate reductase were increased in mitochondria of Pemt-/- mice. Accordingly, ATP levels in hep-atocytes from Pemt-/- mice were double that in Pemt+/+ hepatocytes. We observed a strong correlation between mitochondrial PC-to-PE ratio and cellular ATP levels in hep-atoma cells that expressed various amounts of PEMT. Moreover, mitochondrial respiration was increased in cells lacking PEMT. In the absence of PEMT, changes in mito-chondrial phospholipids caused a shift of pyruvate toward decarboxylation and energy production away from the car-boxylation pathway that leads to glucose production. © 2014 by the American Diabetes Association.