title: Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse.
abstract: Transgenic mice, containing a chimeric gene in which the cDNA for phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C) (EC 4.1.1.32) was linked to the alpha-skeletal actin gene promoter, express PEPCK-C in skeletal muscle (1-3 units/g). Breeding two founder lines together produced mice with an activity of PEPCK-C of 9 units/g of muscle (PEPCK-C(mus) mice). These mice were seven times more active in their cages than controls. On a mouse treadmill, PEPCK-C(mus) mice ran up to 6 km at a speed of 20 m/min, whereas controls stopped at 0.2 km. PEPCK-C(mus) mice had an enhanced exercise capacity, with a VO(2max) 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 degrees 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.
authors: Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4935, USA.
authors: Parvin
authors: P
authors: Hakimi
authors: Jianqi
authors: J
authors: Yang
authors: Gemma
authors: G
authors: Casadesus
authors: Duna
authors: D
authors: Massillon
authors: Fatima
authors: F
authors: Tolentino-Silva
authors: Colleen K
authors: CK
authors: Nye
authors: Marco E
authors: ME
authors: Cabrera
authors: David R
authors: DR
authors: Hagen
authors: Christopher B
authors: CB
authors: Utter
authors: Yacoub
authors: Y
authors: Baghdy
authors: David H
authors: DH
authors: Johnson
authors: David L
authors: DL
authors: Wilson
authors: John P
authors: JP
authors: Kirwan
authors: Satish C
authors: SC
authors: Kalhan
authors: Richard W
authors: RW
authors: Hanson
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal; D003600:Cytosol / Q000201:enzymology*; D004734:Energy Metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology*; D009928:Organ Specificity; D010375:Pedigree; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D012119:Respiration
chemical_list: D010729:Phosphoenolpyruvate Carboxykinase (GTP)
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