Acute consumption of a high-fat diet prior to ischemia-reperfusion results in cardioprotection through NF-κB-dependent regulation of autophagic pathways

Abstract

Previous studies have demonstrated improvement of cardiac function occurs with acute consumption of a high-fat diet (HFD) after myocardial infarction (MI). However, no data exist addressing the effects of acute HFD upon the extent of injury after MI. This study investigates the hypothesis that short-term HFD, prior to infarction, protects the heart against ischemia-reperfusion (I/R) injury through NF-κB-dependent regulation of cell death pathways in the heart. Data show that an acute HFD initiates cardioprotection against MI (>50% reduction in infarct size normalized to risk region) after 24 h to 2 wk of HFD, but protection is completely absent after 6 wk of HFD, when mice are reported to develop pathophysiology related to the diet. Furthermore, cardioprotection after 24 h of HFD persists after an additional 24 h of normal chow feeding and was found to be dependent upon NF-κB activation in cardiomyocytes. This study also indicates that short-term HFD activates autophagic processes (beclin-1, LC-3) preischemia, as seen in other protective stimuli. Increases in beclin-1 and LC-3 were found to be NF-κB-dependent, and administration of chloroquine, an inhibitor of autophagy, abrogated cardioprotection. Our results support that acute high-fat feeding mediates cardioprotection against I/R injury associated with a NF-κB-dependent increase in autophagy and reduced apoptosis, as has been found for ischemic preconditioning.

Simulated ischemia/reperfusion-induced p65-Beclin 1-dependent autophagic cell death in human umbilical vein endothelial cells

“…In agreement with these findings, delayed anesthetic preconditioning protected rat hearts from I/R injury via activation of NF-κB and upregulation of autophagy42. In addition, NF-κB-dependent increase in autophagy is indispensable in cardioprotection as ischemic preconditioning against I/R injury by acute high-fat feeding36. However, autophagy actually is one of the major types of morphologically distinct cell death, called typy II cell death43.…”

“…It is tempting to speculate whether NF-κB is involved in the Beclin 1 associated I/R-induced autophagy. Manipulation of wild type or transgenic IκBα dominant-negative mice unveiled that Beclin-1 and LC-3 are elevated in a NF-κB-dependent manner in the setting of myocardial I/R36. For the first time, our study suggested that Beclin 1 is downstream of NF-κB in the context of sI/R.…”

Endothelial Cell Autophagy in Atherosclerosis is Regulated by miR-30-Mediated Translational Control of ATG6

“…Moreover, some of these studies have demonstrated seemingly different results from our work [43][44][45][46][47][48]. However, we think that these seemingly contradictory data are actually reflections of the complexity of autophagy in the regulation of development of atherosclerosis.…”

Obesity induced by high fat diet attenuates postinfarct myocardial remodeling and dysfunction in adult B6D2F1 mice

“…Third, the model used in previous studies was the Wistar rat fed with a diet containing a high carbohydrate proportion (around 60%) whereas we used a mouse model fed with HFD (60% fat, 20% proteins and 20% carbohydrates) for a longer period (24 vs. 16 weeks). In a recent study, a short period of HFD feeding (from 24 h to 2 weeks) that did not induce obesity resulted in infarct size reduction and preserved function in an in vivo mouse model of transient coronary occlusion, while protection was lost when HFD feeding was extended to 6 weeks [38]. More recently, a comprehensive study by Lopez et al has analyzed the effect of moderated obesity on the myocardial response to a permanent coronary occlusion in aging mice [35].…”