Abstract IA27: Exercise, energy balance, and cancer

PhosphoEnol Pyruvate Carboxy Kinase (PEPCK) catalyzes the GTP dependent conversion of oxaloacetate to CO2 and phospo enol pyruvate, which is subsequently converted to glyceraldehyde-3-phosphate, which then serves as precursor for both gluconeogenesis and/or glyceroneogenesis. Using the mouse gene for the cytoplasmic form of PEPCK-Cmus linked to the skeletal muscle actin promoter, PEPCK-Cmus transgenic mice (TG) were engineered on an SJL/B6 background. The PEPCK-Cmus transgenic mice bear 4 allelic copies of PEPCK; they show a nine-fold overexpression of PEPCK in skeletal muscle associated with an increase in muscle glyceroneogenesis and a 4 fold greater concentration of triglycerides per gram muscle compared with controls. The PEPCK-Cmus TG mice have a remarkable behavioral phenotype of significantly increased and spontaneous exercise, evident from 10 days of age and continuing throughout their extended lifespan. In their home cages, the TG mice show more spontaneous activity, including rearing and running such that they exhibit more than 6 times the physical activity of control mice. Running on a 25° inclined treadmill, the PEPCK-Cmus mice run 25 times further and for longer time periods compared to controls. After 10 minutes treadmill running, the wild type controls show marked increase in Respiratory Exchange Rate (RER) and lactate production, while PEPCK-Cmus TG mice maintain relatively stable RER and lower lactate levels, the latter indicating lipid oxidation to suppo...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Systemic Metabolic Alterations and Cancer: Oral Presentations - Invited Abstracts Source Type: research