Increased Cardiac PFK-2 Protects Against High-Fat Diet-Induced Cardiomyopathy and Mediates Beneficial Systemic Metabolic Effects

<p>Abstract.&nbsp; The healthy heart adapts to changes in nutrient availability and energy demands. In metabolic diseases like type 2 diabetes (T2D), increased reliance on fatty acids for energy production contributes to mitochondrial dysfunction and cardiomyopathy. A principal regulator of cardiac metabolism is 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2), which is a central driver of glycolysis. We hypothesized that increasing PFK-2 activity could mitigate cardiac dysfunction induced by high fat diet (HFD). Wild type (WT) and cardiac-specific transgenic mice expressing PFK-2 (Glyco^Hi) were fed a low fat or HFD for 16-weeks to induce metabolic dysfunction.&nbsp;Metabolic phenotypes were determined by measuring mitochondrial bioenergetics and performing targeted quantitative proteomic and metabolomic analysis. Increasing cardiac PFK-2 had beneficial effects on cardiac and mitochondrial function. Unexpectedly, Glyco^Hi&nbsp;mice also exhibited sex-dependent systemic protection from HFD, including increased glucose homeostasis. These findings support improving glycolysis via PFK-2 activity can mitigate mitochondrial and functional changes that occur with&nbsp;&nbsp;metabolic syndrome.</p> <p>There are two types of data in this upload, proteomics and metabolomics.</p> <p>The proteomics data are raw files acquired on a tsq quantiva triple quadrupole mass spectrometer in the SRM mode at OMRF.&nbsp; Each file is panel of protein assays.&nbsp; Please contact Mike Kinter with questions.</p> <p>The metabolomics data are more processed data files as described in the paper.&nbsp; Please contact Haiwei Gu with questions.</p>