title: Dietary fat supply to failing hearts determines dynamic lipid signaling for nuclear receptor activation and oxidation of stored triglyceride.
abstract: BACKGROUND
  Intramyocardial triglyceride (TG) turnover is reduced in pressure-overloaded, failing hearts, limiting the availability of this rich source of long-chain fatty acids for mitochondrial β-oxidation and nuclear receptor activation. This study explored 2 major dietary fats, palmitate and oleate, in supporting endogenous TG dynamics and peroxisome proliferator-activated receptor-α activation in sham-operated (SHAM) and hypertrophied (transverse aortic constriction [TAC]) rat hearts.
  
  
  RESULTS
  Isolated SHAM and TAC hearts were provided media containing carbohydrate with either (13)C-palmitate or (13)C-oleate for dynamic (13)C nuclear magnetic resonance spectroscopy and end point liquid chromatography/mass spectrometry of TG dynamics. With palmitate, TAC hearts contained 48% less TG versus SHAM (P=0.0003), whereas oleate maintained elevated TG in TAC, similar to SHAM. TG turnover in TAC was greatly reduced with palmitate (TAC, 46.7±12.2 nmol/g dry weight per min; SHAM, 84.3±4.9; P=0.0212), as was β-oxidation of TG. Oleate elevated TG turnover in both TAC (140.4±11.2) and SHAM (143.9±15.6), restoring TG oxidation in TAC. Peroxisome proliferator-activated receptor-α target gene transcripts were reduced by 70% in TAC with palmitate, whereas oleate induced normal transcript levels. Additionally, mRNA levels for peroxisome proliferator-activated receptor-γ-coactivator-1α and peroxisome proliferator-activated receptor-γ-coactivator-1β in TAC hearts were maintained by oleate. With these metabolic effects, oleate also supported a 25% improvement in contractility over palmitate with TAC (P=0.0202).
  
  
  CONCLUSIONS
  The findings link reduced intracellular lipid storage dynamics to impaired peroxisome proliferator-activated receptor-α signaling and contractility in diseased hearts, consistent with a rate-dependent lipolytic activation of peroxisome proliferator-activated receptor-α. In decompensated hearts, oleate may serve as a beneficial energy substrate versus palmitate by upregulating TG dynamics and nuclear receptor signaling.
authors.affiliation: From the Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, IL.
authors.forename: Ryan
authors.initials: R
authors.lastname: Lahey
authors.affiliation: From the Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, IL.
authors.forename: Xuerong
authors.initials: X
authors.lastname: Wang
authors.affiliation: From the Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, IL.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Carley
authors.affiliation: From the Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, IL. dougl@uic.edu.
authors.forename: E Douglas
authors.initials: ED
authors.lastname: Lewandowski
mesh_terms: D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002518:Ceramides / Q000032:analysis; D002952:Citric Acid Cycle; D004041:Dietary Fats / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006333:Heart Failure / Q000178:diet therapy / Q000209:etiology / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000378:metabolism; D008066:Lipolysis; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D019301:Oleic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000502:physiology*; D010168:Palmitates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D002518:Ceramides; D004041:Dietary Fats; D047493:PPAR alpha; D010168:Palmitates; D014280:Triglycerides; D019301:Oleic Acid
keywords: fatty acids; genes; hypertrophy; lipids; metabolism