Meeting Abstract

P1.161  Wednesday, Jan. 4  β-GPA treatment leads to elevated basal metabolic rate and enhanced exercise tolerance in mice. ROSS, T.T.*; KINSEY, S.T.; Univ. of North Carolina Wilmington; Univ. of North Carolina Wilmington

Hypoxia acclimation leads to reduced phosphocreatine (PCr) and elevated AMP in mouse skeletal muscle. While these metabolic changes are associated with improved hypoxic exercise capacity, there is no increase in AMP kinase (AMP-K) phosphorylation or mitochondrial biogenesis during chronic hypoxia. We investigated the effect of experimentally manipulated PCr and AMP on basal metabolic rate (BMR) and normoxic and hypoxic exercise tolerance (NET; HET) in C57BL/6J (B6) mice. Intramuscular concentrations of PCr were decreased by dietary administration of 1% β-guanidinopropionic acid (β-GPA), a creatine analog, for either 2 or 6 weeks. 31P-NMR of gastrocnemius confirmed that PCr /ATP ratios were significantly decreased in both the 2 week (27%) and 6-week (54 %) β-GPA treated mice. BMR was increased by 64% after 2 weeks, but only by 37% after 6 weeks of β-GPA treatment. NET was decreased by 35% after 2 weeks but was not changed after 6 weeks of β-GPA treatment. HET also decreased by 27% after 2 weeks, but in contrast to NET, increased by 23% after 6 weeks of β-GPA treatment. The large increase in BMR and the decrease in NET and HET seen following the 2-week β-GPA treatment probably reflect compromised muscle and cardiovascular function due to extensive AMP-K induced tissue remodeling associated with this acute energetic stress. The more modest elevation in BMR seen in the 6-week β-GPA treatment probably reflects the new steady-state BMR where mitochondrial density in muscle and other tissues is elevated. The fact that the 6-week β-GPA treatment resulted in an enhanced HET, but not NET, suggest an advantage of a reduced energy state on hypoxic exercise.