Hyperpolarized [1-¹³C] pyruvate MRSI reveals a diet-dependent metabolic shift in ZSF1 rats

Abstract

We evaluated altered cardiac metabolism in Zucker Spontaneously Hypertensive Fatty (ZSF1) rats fed an isocaloric high-fat diet versus normal chow using hyperpolarized (HP) [1-¹³C]pyruvate MR spectroscopic imaging (MRSI). This technique exploits remarkable signal enhancement to track the metabolic fate of injected HP [1-¹³C]pyruvate in vivo, allowing a simultaneous assessment of multiple metabolic pathways. The conversion of [1-¹³C]pyruvate to [1-¹³C]lactate (Lac) reflects anaerobic glycolysis activity, while the detection of ¹³C-bicarbonate (Bic) indicates glucose oxidation. Our findings show that ZSF1 rats fed a high-fat diet exhibit a greater reliance on anaerobic glycolysis relative to glucose oxidation, and this metabolic shift can be detected in vivo in real time. This study demonstrates the feasibility of HP [1-¹³C]pyruvate MRSI for assessing diet-dependent metabolic shifts in the myocardium of ZSF1 obese rats, a widely used preclinical model for heart failure with preserved ejection fraction (HFpEF).