title: Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion.
abstract: High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulin-ketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Cardiovascular Research Institute, National University Health System, National University of Singapore, Singapore; and.
authors.forename: Peipei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Douglas
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Tate
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Simon
authors.initials: S
authors.lastname: Sham
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Birmingham VA Medical Center, Birmingham, Alabama slloyd@uabmc.edu.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Lloyd
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D000818:Animals; D002952:Citric Acid Cycle; D050528:Diet, Carbohydrate-Restricted / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D000067268:Isolated Heart Preparation; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D016277:Ventricular Function, Left
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D051057:Proto-Oncogene Proteins c-akt; D020155:3-Hydroxybutyric Acid
keywords: diet; insulin; metabolism; myocardial ischemia-reperfusion injury