In:
Cardiovascular Research, Oxford University Press (OUP), ( 2024-01-09)
Abstract:
Heart failure with preserved ejection fraction (HFpEF) is a prevalent disease worldwide. While it is well established that alterations of cardiac energy metabolism contribute to cardiovascular pathology, the precise source of fuel used by the heart in HFpEF remain unclear. The objective of this study was to define the energy metabolic profile of the heart in HFpEF. Methods and Results 8-week-old C57BL/6 male mice were subjected to a ‘2-Hit’ HFpEF protocol (60% high-fat diet (HFD) + 0.5 g/L of Nω-nitro-L-arginine methyl ester (L-NAME)). Echocardiography and pressure-volume loop analysis were used for assessing cardiac function and cardiac hemodynamics respectively. Isolated working hearts were perfused with radiolabeled energy substrates to directly measure rates of fatty acid oxidation, glucose oxidation, ketone oxidation, and glycolysis. HFpEF mice exhibited increased body weight, glucose intolerance, elevated blood pressure, diastolic dysfunction, and cardiac hypertrophy. In HFpEF hearts, insulin stimulation of glucose oxidation was significantly suppressed. This is paralleled with an increase in fatty acid oxidation rates, while cardiac ketone oxidation and glycolysis rates were comparable to healthy control hearts. The balance between glucose and fatty acid oxidation contributing to overall adenosine triphosphate (ATP) production was disrupted, where HFpEF hearts were more reliant on fatty acid as the major source of fuel for ATP production, compensating for the decrease of ATP originating from glucose oxidation. Additionally, p-PDH (pyruvate dehydrogenase) levels decreased in both HFpEF mice and human patients heart samples. Conclusions In HFpEF, fatty acid oxidation dominates as the major source of cardiac ATP production at the expense of insulin stimulated glucose oxidation.
Type of Medium:
Online Resource
ISSN:
0008-6363
,
1755-3245
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2024
detail.hit.zdb_id:
1499917-1
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