The Concentration of Phosphatidylethanolamine in Mitochondria Can Modulate ATP Production and Glucose Metabolism in Mice

  1. Dennis E. Vance1,2
  1. 1Group on Molecular and Cell Biology of Lipids, the Alberta Diabetes Institute, the Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada
  2. 2Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada
  3. 3Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
  1. Corresponding author: Dennis E. Vance, dennis.vance{at}ualberta.ca.

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 gluconeogenesis. 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 hepatocytes 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 hepatoma cells that expressed various amounts of PEMT. Moreover, mitochondrial respiration was increased in cells lacking PEMT. In the absence of PEMT, changes in mitochondrial phospholipids caused a shift of pyruvate toward decarboxylation and energy production away from the carboxylation pathway that leads to glucose production.

  • Received June 25, 2013.
  • Accepted March 18, 2014.
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This Article

  1. Diabetes vol. 63 no. 8 2620-2630
  1. All Versions of this Article:
    1. db13-0993v1
    2. 63/8/2620 most recent