title: 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.
authors.affiliation: Department of Systems Biology and Physiology, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Lauren
authors.initials: L
authors.lastname: Haar
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Sheryl E
authors.initials: SE
authors.lastname: Koch
authors.affiliation: Department of Molecular Pharmacology and Therapeutics Loyola University Chicago, Maywood, Illinois; and Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Jillian
authors.initials: J
authors.lastname: Goines
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Michael
authors.initials: M
authors.lastname: Tranter
authors.affiliation: Department of Systems Biology and Physiology, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Engevik
authors.affiliation: Department of Systems Biology and Physiology, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Michelle
authors.initials: M
authors.lastname: Nieman
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Jack
authors.initials: J
authors.lastname: Rubinstein
authors.affiliation: Department of Molecular Pharmacology and Therapeutics Loyola University Chicago, Maywood, Illinois; and Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio wjones7@luc.edu.
authors.forename: W Keith
authors.initials: WK
authors.lastname: Jones
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D059305:Diet, High-Fat; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000178:diet therapy* / Q000378:metabolism / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B
keywords: NF-κB; autophagy; high fat; ischemia-reperfusion injury; preconditioning