Abstract P3196: Voluntary Exercise Training Does Not Prevent High Phosphate Diet-induced Mitochondrial Dysfunction

Abstract

Inorganic phosphate (Pi) is used extensively as a preservative and a flavor enhancer in processed foods consumed as part of a Western diet. Mice fed high-Pi diet (HP) for 12 weeks display decreased maximal exercise capacity but no change in cardiac function. Expression of fatty acid metabolism genes are decreased and expression of glucose metabolism genes are increased in skeletal muscle after HP diet. Consequently, mitochondrial function is significantly impaired in skeletal muscle from mice fed HP diet. In the current study we test the hypothesis that voluntary exercise training prevents the negative metabolic consequences of HP diet. We housed mice in voluntary wheel running cages and fed them a normal-Pi (NP) or HP diet. HP diet did not alter body weight or composition, and NP- and HP-fed mice voluntarily ran the same distance in wheel cages throughout the study. Using incline treadmill exercise tolerance tests we observed no differences in medium-intensity exercise capacity between NP- and HP-fed mice subjected to voluntary wheel running, contrary to findings in sedentary mice. Despite preserved exercise capacity, muscle mitochondrial function in mice fed HP diet was significantly decreased after 5 weeks, which continued to decline after 12 weeks of HP diet and voluntary exercise. To investigate mechanisms of HP-induced mitochondrial dysfunction we measured expression of key metabolic genes and found that fatty acid metabolism genes were significantly decreased in muscle from mice fed HP diet and subjected to voluntary exercise. These data suggest that voluntary exercise training does not prevent the negative metabolic consequences of consuming a high-phosphate diet. Thus, dietary Pi may represent a novel and modifiable target to reduce physical inactivity associated with the Western diet.