Abstract

Background & ObjectivesHigh fat or high sugar diets are associated with increased risk for coronary heart disease but have not been found to exacerbate cardiac dysfunction in rodent models of heart failure. We thus tested the effect of HF diet in a mouse model of diabetes and its associated cardiac dysfunction.MethodsFive‐week‐old C57Bl6J male mice received either standard (Std) or HF diet for 2 weeks, then received multiple injections of either low doses (40 mg/kg) of streptozotocin (STZ) or vehicle (Veh).ResultsTen weeks after STZ injections (and compared to Std‐Veh mice), both STZ groups displayed similar (i) fasting plasma glucose and insulin levels, which were respectively increased and decreased (p<0.001) and (ii) cardiac systolic dysfunction, as evidenced by a 8% lower ejection fraction (p<0.05) at echocardiography. However, the increase in plasma levels of ketone bodies, glycated haemoglobin and branched chain amino acids was smaller (p<0.05) in HF‐STZ mice than in Std‐STZ at both 6 and 12 weeks. Likewise, HF‐STZ mice maintained (in contrast to Std‐STZ mice) body weight and epidydymal fat mass as well as Std‐Veh.ConclusionNot only did HF not exacerbate diabetes‐induced cardiac dysfunction, but it even attenuated the systemic metabolic alterations induced by STZ, which may in the long term delay the development of heart failure. (Supported by CIHR & HSFC)

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