Regulation of Substrate Oxidation in Isolated Myocardial Cells by β-Hydroxybutyrate

Abstract

The role of ketone bodies in myocardial substrate oxidation was examined using freshly isolated Ca2+-tolerant heart myocytes, beta-hydroxybutyrate (beta OHB) inhibited lactate oxidation by the myocytes by 30-60%, and the inhibition was concentration dependent. Palmitate oxidation was also markedly decreased, whereas octanoate oxidation was only minimally affected by the presence of beta OHB. Lactate, octanoate, or palmitate had little, if any, effect on beta OHB oxidation. beta OHB oxidation was reduced by 22-28% in myocytes isolated from chronically diabetic rats, whereas the oxidation of palmitate remained similar to the controls. However, beta OHB still inhibited palmitate oxidation to the same extent as in the control cells. Our data support the role of beta OHB as a physiologic regulator of myocardial substrate metabolism.

Stereoselective effects of 3-hydroxybutyrate on glucose utilization of rat cardiomyocytes

“…In addition, the heart was also chosen because ketone bodies competed with glucose (Chen et al, 1984), fatty acid (Forsey et al, 1987) or palmitate (Vanoverschelde et al, 1993) as the metabolic fuel for the heart. Table 1 depicts the distributions of d-and l-3HB in these organs.…”

1H-NMR-Based Metabolic Analysis of Human Serum Reveals Novel Markers of Myocardial Energy Expenditure in Heart Failure Patients

“…More importantly, we found that these ketone bodies level were significantly associated with increasing myocardial energy consumption. Some studies have reported that oxidation and utilization of ketone bodies could inhibit the oxidation of fatty acids by the myocardium [26], [27]. Hence, increase of ketone bodies can promote the conversion of myocardial energy consumption from adult myocardium substrate (i.e., fatty acids) to the embryonal myocardium substrate in HF.…”

Using positron emission tomography to study human ketone body metabolism: A review

“…It is well documented that fatty acids are the preferred myocardial fuel substrate, with a shift toward increased use of glucose, lactate and ketones during acutely increased demand [59,60]. This can be altered in various pathologies -the diabetic heart, for instance, relies more on fatty acid than glucose as oxidative fuel source [61], and in vitro studies suggest that ketone bodies inhibit fatty acid oxidation in diabetic cardiomyocytes [62,63], which also appear to have impaired ketone oxidation when compared with healthy cardiomyocytes [62]. Interestingly, acute ketone infusion in non-diabetic pigs inhibits myocardial fatty acid oxidation, but not glucose oxidation, when administered together with a fat emulsion [64].…”

“…At the same time, however, an opposing effect has been shown with shorter exposure to ketone bodies (betahydroxybutyrate and acetoacetate in a 4:1 ratio) together with insulin, a combination that appears to potentiate the metabolic effects of insulin on cardiomyocytes reflected by decreased O 2 use and increased mechanic efficiency [68]. Ketone bodies also decrease lactate oxidation in a concentration-dependent manner and decrease palmitate oxidation but not oxidation of octanoate, a medium chain fatty acid [62]. Controversy surrounds the effect of ketone bodies on myocardial contractility, since some studies report increased contractility [69] whereas others in contrast indicate that ketone bodies as the sole energy source result in decreased myocardial contractility [70].…”