Abstract

Clinical evidence shows that patients with high serum cholesterol levels have better survival rates following cardiac ischemic injury than those with lower levels, though the mechanism for such a phenomenon is unclear. Previous studies using a rat model of heart failure associated with LV disfunction, paired with chronic high fat feeding confirm that a high fat diet induces improvement in myocardial function and modulation of cardioprotective gene profiles. This study addresses the hypothesis that acute high fat feeding initiates a systemic signaling cascade that confers cardioprotection and improves in vivo myocardial function following ischemia/reperfusion (I/R) injury. Our results show that mice fed a high fat diet for 24 h to 2 wk were protected against subsequent I/R injury (30 min LAD occlusion) as assessed by echocardiographic measurements of cardiac function and infarct size (~70% reduction vs. control diet, P≤0.05). However, cardioprotection was not observed after more chronic feeding (6 wks), indicating that this effect is independent of any potential chronic effects of high fat feeding (serum cholesterol change, obesity, diabetes, etc.). In addition, mice fed a high fat diet for 24 h then returned to control diet for 24 h prior to I/R maintained a prolonged or ‘late phase’ protection against I/R injury. In conclusion, acute high fat feeding elicits a cardioprotective effect and preserves cardiac function in a mouse model of I/R injury. Studies to elucidate the factors that initiate and mediate this novel cardioprotective phenomenon are being pursued. This work was supported by NIH RO1HL091478 (WKJ), 2010 Rhen Award (JR) NIH T32HL007382 (LH)

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