Enhancing cardiac glycolysis causes an increase in PDK4 content in response to short term high fat diet

Cardiac metabolic flexibility is essential for proper function. Under pathological conditions, such as diabetes, the heart increases reliance on fatty acid oxidation at the expense of glucose metabolism. Thus, restoring or enhancing glucose usage may provide a therapeutic strategy. In this study we sought to identify how the cardiac proteomic profile is affected basally and after a short term high fat diet (7d) in wild type and a transgenic model of enhanced glycolysis (Glyco^Hi). Targeted quantitative proteomics and cluster analysis revealed revealed Glyco^Hi mice have increased protein expression of glycolytic enzymes and that this was sustained with the high fat diet challenge. Glyco^Hi mice also had significantly increased expression of pyruvate dehydrogenase kinase 4 (PDK4), an enzyme that regulates the overall rate of glucose oxidation. These results support that Glyco^Hi mice have the capacity to increase glycolysis when challenged with a nutrient stress but that there is a compensatory increase in PDK4 that may limit the overall rate of glucose oxidation.