期刊
CARDIOVASCULAR RESEARCH
卷 115, 期 11, 页码 1606-1616出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvz045
关键词
Beta-hydroxybutyrate; Cardiac Energy metabolism; Ketone body oxidation; Heart failure; Hypertrophy
资金
- National Institutes of Health [NIH R01HL12849-04]
- Canadian Institutes of Health Research
- Motyl Graduate Studentship in Cardiac Sciences from the University of Alberta Faculty of Medicine and Dentistry
- Alberta Diabetes Institute
Aims The failing heart is energy-starved and inefficient due to perturbations in energy metabolism. Although ketone oxidation has been shown recently to increase in the failing heart, it remains unknown whether this improves cardiac energy production or efficiency. We therefore assessed cardiac metabolism in failing hearts and determined whether increasing ketone oxidation improves cardiac energy production and efficiency. Methods and results C57BL/6J mice underwent sham or transverse aortic constriction (TAC) surgery to induce pressure overload hypertrophy over 4-weeks. Isolated working hearts from these mice were perfused with radiolabelled beta-hydroxybutyrate (beta OHB), glucose, or palmitate to assess cardiac metabolism. Ejection fraction decreased by 45% in TAC mice. Failing hearts had decreased glucose oxidation while palmitate oxidation remained unchanged, resulting in a 35% decrease in energy production. Increasing beta OHB levels from 0.2 to 0.6 mM increased ketone oxidation rates from 251 +/- 24 to 834 +/- 116 nmol.g dry wt(-1) . min(-1) in TAC hearts, rates which were significantly increased compared to sham hearts and occurred without decreasing glycolysis, glucose, or palmitate oxidation rates. Therefore, the contribution of ketones to energy production in TAC hearts increased to 18% and total energy production increased by 23%. Interestingly, glucose oxidation, in parallel with total ATP production, was also significantly upregulated in hearts upon increasing beta OHB levels. However, while overall energy production increased, cardiac efficiency was not improved. Conclusions Increasing ketone oxidation rates in failing hearts increases overall energy production without compromising glucose or fatty acid metabolism, albeit without increasing cardiac efficiency.
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