Journal ArticleDOI
Myocardial Fatty Acid Metabolism in Health and Disease
TLDR
The regulation of myocardial fatty acid beta-oxidation is reviewed and how alterations in fatty acid Beta-Oxidation can contribute to heart disease is discussed.Abstract:
There is a constant high demand for energy to sustain the continuous contractile activity of the heart, which is met primarily by the β-oxidation of long-chain fatty acids. The control of fatty acid β-oxidation is complex and is aimed at ensuring that the supply and oxidation of the fatty acids is sufficient to meet the energy demands of the heart. The metabolism of fatty acids via β-oxidation is not regulated in isolation; rather, it occurs in response to alterations in contractile work, the presence of competing substrates (i.e., glucose, lactate, ketones, amino acids), changes in hormonal milieu, and limitations in oxygen supply. Alterations in fatty acid metabolism can contribute to cardiac pathology. For instance, the excessive uptake and β-oxidation of fatty acids in obesity and diabetes can compromise cardiac function. Furthermore, alterations in fatty acid β-oxidation both during and after ischemia and in the failing heart can also contribute to cardiac pathology. This paper reviews the regulation of myocardial fatty acid β-oxidation and how alterations in fatty acid β-oxidation can contribute to heart disease. The implications of inhibiting fatty acid β-oxidation as a potential novel therapeutic approach for the treatment of various forms of heart disease are also discussed.read more
Citations
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Journal ArticleDOI
Obesity and the risk of heart failure
TL;DR: In this large, community-based sample, increased body-mass index was associated with an increased risk of heart failure and strategies to promote optimal body weight may reduce the population burden ofheart failure.
Journal ArticleDOI
Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics
TL;DR: How ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient states and protect from inflammation and injury in multiple organ systems is discussed.
Journal ArticleDOI
Cardiac metabolism in heart failure: implications beyond ATP production.
TL;DR: It is highlighted that metabolic remodeling in HF not only results in impaired cardiac energetics but also induces other processes implicated in the development of HF such as structural remodeling and oxidative stress, which may have significant therapeutic relevance that goes beyond the energetic aspect.
Journal ArticleDOI
CV Protection in the EMPA-REG OUTCOME Trial: A "Thrifty Substrate" Hypothesis.
TL;DR: It is hypothesized that under conditions of mild, persistent hyperketonemia, such as those that prevail during treatment with SGLT2 inhibitors, β-hydroxybutyrate is freely taken up by the heart and oxidized in preference to fatty acids, which improves the transduction of oxygen consumption into work efficiency at the mitochondrial level.
Journal ArticleDOI
SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review
Subodh Verma,John J.V. McMurray +1 more
TL;DR: The role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function is focused on.
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