Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse

enhanced exercise capacity, with a VO2max of 156 8.0 ml/kg/min, a maximal respiratory exchange ratio of 0.91 0.03, and a blood lactate concentration of 3.7 1.0 mM after running for 32 min at a 25° grade; the values for control animals were 112 21 ml/kg/min, 0.99 0.08, and 8.1 5.0 mM respectively. The PEPCK-C mus mice ate 60% more than controls but had half the body weight and 10% the body fat as determined by magnetic resonance imaging. In addition, the number of mitochondria and the content of triglyceride in the skeletal muscle of PEPCK-C mus mice were greatly increased as compared with controls. PEPCK-C mus mice had an extended life span relative to control animals; mice up to an age of 2.5 years ran twice as fast as 6 –12-month-old control animals. We conclude that overexpression of PEPCK-C repatterns energy metabolism and leads to greater longevity.