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Central question • Does obesity with insulin resistance decrease left ventricular pump function and/or myocardial tolerance to ischaemia in a rodent model of metabolic syndrome and, • What mechanisms are involved in these changes? Findings and its importance • These data suggest that although left ventricular pump function may be maintained with obesity and insulin resistance, the hearts from these animals are more prone to ischaemia/reperfusion injury which is in part due to changes in the functionality of the myocardial RISK pathway. • Interventions/therapies aimed at normalising RISK pathway function have the potential to normalise myocardial tolerance to ischaemia/reperfusion in patients with the metabolic syndrome