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Review
. 2020 Sep 16:11:570421.
doi: 10.3389/fphys.2020.570421. eCollection 2020.

Myocardial Energy Metabolism in Non-ischemic Cardiomyopathy

Amanda A Greenwell  1   2   3 , Keshav Gopal  1   2   3 , John R Ussher  1   2   3
Affiliations
Review

Myocardial Energy Metabolism in Non-ischemic Cardiomyopathy

Amanda A Greenwell et al. Front Physiol. .

Abstract

As the most metabolically demanding organ in the body, the heart must generate massive amounts of energy adenosine triphosphate (ATP) from the oxidation of fatty acids, carbohydrates and other fuels (e.g., amino acids, ketone bodies), in order to sustain constant contractile function. While the healthy mature heart acts omnivorously and is highly flexible in its ability to utilize the numerous fuel sources delivered to it through its coronary circulation, the heart's ability to produce ATP from these fuel sources becomes perturbed in numerous cardiovascular disorders. This includes ischemic heart disease and myocardial infarction, as well as in various cardiomyopathies that often precede the development of overt heart failure. We herein will provide an overview of myocardial energy metabolism in the healthy heart, while describing the numerous perturbations that take place in various non-ischemic cardiomyopathies such as hypertrophic cardiomyopathy, diabetic cardiomyopathy, arrhythmogenic cardiomyopathy, and the cardiomyopathy associated with the rare genetic disease, Barth Syndrome. Based on preclinical evidence where optimizing myocardial energy metabolism has been shown to attenuate cardiac dysfunction, we will discuss the feasibility of myocardial energetics optimization as an approach to treat the cardiac pathology associated with these various non-ischemic cardiomyopathies.

Keywords: cardiac function; cardiomyopathy; energy metabolism; fatty acid oxidation; glucose oxidation.

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Figures

FIGURE 1
FIGURE 1
Intermediary energy metabolism in the cardiac myocyte. Illustration depicts intermediary metabolism of carbohydrates (glucose), fatty acids, and ketone bodies (βOHB) in the myocardium. Key nodes depicting the control of uptake into the cardiac myocyte, uptake into the mitochondria, and subsequent metabolism to acetyl CoA are highlighted. Acetyl CoA from the oxidation of carbohydrates, fatty acids, and ketone bodies is subsequently metabolized further in the Krebs Cycle. This results in the formation of reducing equivalents (e.g., FADH2/NADH) that donate their electrons to the complexes of the electron transport chain, driving oxidative phosphorylation and the ATP generation needed for sustaining contractile function. ACAT, acetoacetyl CoA thiolase; ACC, acetyl CoA carboxylase; BDH, β-hydroxybutyrate dehydrogenase; βOHB, β-hydroxybutyrate; CD36, cluster of differentiation 36; CPT, carnitine palmitoyl transferase; CT, carnitine translocase; FACS, fatty acyl CoA synthetase; FADH2, reduced flavin adenine dinucleotide; FATP, fatty acid transport protein; GLUT, glucose transporter; LPL, lipoprotein lipase; MCD, malonyl CoA decarboxylase; MCT, monocarboxylic acid transporter; MPC, mitochondrial pyruvate carrier; NADH, reduced nicotinamide adenine dinucleotide; PDH, pyruvate dehydrogenase; PDHK, PDH kinase; PDHP, PDH phosphatase; SCOT, succinyl CoA:3-ketoacid CoA transferase; TAG, triacylglycerol; VLDL, very-low density lipoprotein.
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