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Circulation. 2014 Nov 11;130(20):1790-9. doi: 10.1161/CIRCULATIONAHA.114.011687. Epub 2014 Sep 29.

Dietary fat supply to failing hearts determines dynamic lipid signaling for nuclear receptor activation and oxidation of stored triglyceride.

Author information

1
From the Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, IL.
2
From the Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, IL. dougl@uic.edu.

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.

METHODS AND 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.

KEYWORDS:

fatty acids; genes; hypertrophy; lipids; metabolism

PMID:
25266948
PMCID:
PMC4229424
DOI:
10.1161/CIRCULATIONAHA.114.011687
[Indexed for MEDLINE]
Free PMC Article

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