Sex differences in myocardial ketone oxidation capacity in cardiometabolic disease with coincident ischemic heart disease

Male HFpEF-MI mice show reduced cardiac ketolytic enzyme expression with elevated circulating ketone bodies and higher mortality than female HFpEF-MI mice.

• Why it matters: Sex-linked vulnerability in HFpEF patients after myocardial infarction is worse in men, but the molecular basis is unclear.
• What they did: In diabetes-associated ischemic heart disease patients, cardiac BDH1 and OXCT1 abundance was measured by sex; in mice, HFpEF was induced by 10 weeks of high-fat diet plus L-NAME followed by coronary artery ligation, then ketone oxidative capacity, circulating ketone bodies, function, and survival were assessed.
• The result: BDH1 and OXCT1 were reduced in male patients but preserved in females, and in mice MI impaired systolic function in both sexes; male HFpEF-MI mice had reduced cardiac ketolytic enzymes with elevated circulating ketone bodies, while females maintained cardiac ketone oxidative capacity and improved survival.

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