title: High-fat, low-carbohydrate diet promotes arrhythmic death and increases myocardial ischemia-reperfusion injury in rats.
abstract: High-fat, low-carbohydrate diets (HFLCD) are often eaten by humans for a variety of reasons, but the effects of such diets on the heart are incompletely understood. We evaluated the impact of HFLCD on myocardial ischemia/reperfusion (I/R) using an in vivo model of left anterior descending coronary artery ligation. Sprague-Dawley rats (300 g) were fed HFLCD (60% calories fat, 30% protein, 10% carbohydrate) or control (CONT; 16% fat, 19% protein, 65% carbohydrate) diet for 2 wk and then underwent open chest I/R. At baseline (preischemia), diet did not affect left ventricular (LV) systolic and diastolic function. Oil red O staining revealed presence of lipid in the heart with HFLCD but not in CONT. Following I/R, recovery of LV function was decreased in HFLCD. HFLCD hearts exhibited decreased ATP synthase and increased uncoupling protein-3 gene and protein expression. HFLCD downregulated mitochondrial fusion proteins and upregulated fission proteins and store-operated Ca(2+) channel proteins. HFLCD led to increased death during I/R; 6 of 22 CONT rats and 16 of 26 HFLCD rats died due to ventricular arrhythmias and hemodynamic shock. In surviving rats, HFLCD led to larger infarct size. We concluded that in vivo HFLCD does not affect nonischemic LV function but leads to greater myocardial injury during I/R, with increased risk of death by pump failure and ventricular arrhythmias, which might be associated with altered cardiac energetics, mitochondrial fission/fusion dynamics, and store-operated Ca(2+) channel expression.
authors.affiliation: Departments of Medicine and.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Cardiovascular Research Institute, National University Health System, National University of Singapore, Singapore, Singapore;
authors.forename: Peipei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Pathology, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Luyun
authors.initials: L
authors.lastname: Zou
authors.affiliation: Departments of Medicine and.
authors.forename: Jing
authors.initials: J
authors.lastname: Qu
authors.affiliation: Pathology, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Silvio
authors.initials: S
authors.lastname: Litovsky
authors.affiliation: Departments of Medicine and.
authors.forename: Patrick
authors.initials: P
authors.lastname: Umeda
authors.affiliation: Departments of Medicine and.
authors.forename: Lufang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Pathology, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: John
authors.initials: J
authors.lastname: Chatham
authors.affiliation: Department of Clinical Pharmacology, Washington State University, Pullman, Washington;
authors.forename: Susan A
authors.initials: SA
authors.lastname: Marsh
authors.affiliation: Departments of Medicine and Birmingham VA Medical Center, Birmingham, Alabama.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Dell'Italia
authors.affiliation: Departments of Medicine and Birmingham VA Medical Center, Birmingham, Alabama sglloyd@uab.edu.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Lloyd
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D050528:Diet, Carbohydrate-Restricted / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071247:Uncoupling Protein 3; D016276:Ventricular Function
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604392:UCP3 protein, human; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3
keywords: arrhythmia; diet; mitochondria; myocardial ischemia; reperfusion injury