期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
卷 1865, 期 12, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbalip.2020.158813
关键词
Ketone body; Heart failure; Sodium glucose co-transporter 2 inhibitors; Fatty acid oxidation; Glucose oxidation; NLRP3 inflammasome
资金
- Canadian Institutes of Health Research
- Alberta Innovates Postgraduate Fellowship in Health Innovation
- Alberta Innovates Graduate Studentship
- Motyl Graduate Studentship in Cardiac Sciences from the University of Alberta Faculty of Medicine and Dentistry
- Alberta Diabetes Institute
- Sir Frederick Banting and Dr. Charles Best Canada Graduate Scholarship-Masters from the Canadian Institutes of Health Research
- Walter H Johns Graduate Fellowship from the University of Alberta
- Maternal and Child Health (MatCH) Scholarship Program at the University of Alberta, Faculty of Medicine and Dentistry
The high energy demands of the heart are met primarily by the mitochondrial oxidation of fatty acids and glucose. However, in heart failure there is a decrease in cardiac mitochondrial oxidative metabolism and glucose oxidation that can lead to an energy starved heart. Ketone bodies are readily oxidized by the heart, and can provide an additional source of energy for the failing heart. Ketone oxidation is increased in the failing heart, which may be an adaptive response to lessen the severity of heart failure. While ketone have been widely touted as a thrifty fuel, increasing ketone oxidation in the heart does not increase cardiac efficiency (cardiac work/oxygen consumed), but rather does provide an additional fuel source for the failing heart. Increasing ketone supply to the heart and increasing mitochondrial ketone oxidation increases mitochondrial tricarboxylic acid cycle activity. In support of this, increasing circulating ketone by iv infusion of ketone bodies acutely improves heart function in heart failure patients. Chronically, treatment with sodium glucose co-transporter 2 inhibitors, which decreases the severity of heart failure, also increases ketone body supply to the heart. While ketogenic diets increase circulating ketone levels, minimal benefit on cardiac function in heart failure has been observed, possibly due to the fact that these dietary regimens also markedly increase circulating fatty acids. Recent studies, however, have suggested that administration of ketone ester cocktails may improve cardiac function in heart failure. Combined, emerging data suggests that increasing cardiac ketone oxidation may be a therapeutic strategy to treat heart failure.
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