Dietary Fat Supply to Failing Hearts Determines Dynamic Lipid Signaling for Nuclear Receptor Activation and Oxidation of Stored Triglyceride

Article

关键词: CARNITINE PALMITOYLTRANSFERASE-I;    ENERGY-METABOLISM;    CARDIAC-HYPERTROPHY;    GENE-EXPRESSION;    INTACT HEART;    PPAR-ALPHA;    RAT-HEART;    SUBSTRATE;    FLUX;    FAILURE;   

DOI  :  10.1161/CIRCULATIONAHA.114.011687

来源: SCIE

【 摘 要 】

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 -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- activation in sham-operated (SHAM) and hypertrophied (transverse aortic constriction [TAC]) rat hearts. Methods and Results Isolated SHAM and TAC hearts were provided media containing carbohydrate with either C-13-palmitate or C-13-oleate for dynamic C-13 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, 46.712.2 nmol/g dry weight per min; SHAM, 84.3 +/- 4.9; P=0.0212), as was -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- 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--coactivator-1 and peroxisome proliferator-activated receptor--coactivator-1 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- signaling and contractility in diseased hearts, consistent with a rate-dependent lipolytic activation of peroxisome proliferator-activated receptor-. In decompensated hearts, oleate may serve as a beneficial energy substrate versus palmitate by upregulating TG dynamics and nuclear receptor signaling.

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