Effect of murine strain on metabolic pathways of glucose production after brief or prolonged fasting

1 Mary Nell and Ralph B. Rogers Magnetic Resonance Center, University of Texas Southwestern Medical Center, Dallas; 3 Department of Chemistry, University of Texas at Dallas; 2 Department of Cell and Molecular Biology, Lund University, Lund, Sweden; and 4 Research and Development Service, Veterans Affairs North Texas Health Care System, Dallas, Texas Submitted 21 December 2004 ; accepted in final form 14 February 2005 Background strain is known to influence the way a genetic manipulation affects mouse phenotypes. Despite data that demonstrate variations in the primary phenotype of basic inbred strains of mice, there is limited data available about specific metabolic fluxes in vivo that may be responsible for the differences in strain phenotypes. In this study, a simple stable isotope tracer/NMR spectroscopic protocol has been used to compare metabolic fluxes in ICR, FVB/N (FVB), C57BL/6J (B6), and 129S1/SvImJ (129) mouse strains. After a short-term fast in these mice, there were no detectable differences in the pathway fluxes that contribute to glucose synthesis. However, after a 24-h fast, B6 mice retain some residual glycogenolysis compared with other strains. FVB mice also had a 30% higher in vivo phospho enol pyruvate carboxykinase flux and total glucose production from the level of the TCA cycle compared with B6 and 129 strains, while total body glucose production in the 129 strain was 30% lower than in either FVB or B6 mice. These data indicate that there are inherent differences in several pathways involving glucose metabolism of inbred strains of mice that may contribute to a phenotype after genetic manipulation in these animals. The techniques used here are amenable to use as a secondary or tertiary tool for studying mouse models with disruptions of intermediary metabolism. nuclear magnetic resonance; tricarboxylic acid cycle; phospho enol pyruvate carboxykinase; metabolic flux; stable isotope tracers; deuterium; mouse phenotype Address for reprint requests and other correspondence: S. Burgess, Mary Nell and Ralph B. Rogers Magnetic Resonance Center, 5801 Forest Park Road, Dallas, TX 75235-9085 (e-mail: shawn.burgess{at}utsouthwestern.edu )