Switching Back to Normal Diet Following High-Fat Diet Feeding Reduces Cardiac Vulnerability to Ischaemia and Reperfusion Injury

Abstract

Background: We have recently shown that hearts of mice fed high-fat diet exhibit increased vulnerability to ischaemia and reperfusion (I/R) in parallel to changes in catalase protein expression, mitochondrial morphology and intracellular diastolic Ca²⁺. Aims: To determine whether switching from high-fat back to normal diet alters vulnerability to I/R and to investigate cardiac cellular remodelling in relation to the mechanism(s) underlying I/R injury. Methods and Results: Male C57BL/6J mice were fed a high-fat diet for 19-22 weeks; after which a subset of mice was switched back to normal diet for 4-6 weeks. Hearts from mice switched back to normal diet were more resistant to reperfusion injury compared to hearts from mice fed only high-fat diet. This was associated with a significant reversal in catalase expression (western blotting) and recovery of size and density of mitochondria (electron microscopy). In contrast, switching back to normal diet did not alter cardiomyocyte contractility or Ca²⁺ transients compared to high-fat diet. Conclusion: This study shows for the first time that switching the diet from high-fat back to normal reduces vulnerability to I/R. This effect is associated with changes in catalase levels and mitochondrial morphology without altering cardiomyocyte contractility or Ca²⁺ transients.