Background
High-fat diet (HFD) induces systemic insulin resistance leading to myocardial dysfunction. We
Conclusions
HFD-induced IR associated with increased glucose utility undergoing oxidative phosphorylation via the TCA cycle in the myocardium is supported by overexpression of glucose transporter, acetyl-CoA synthase. Noninvasive imaging biomarker has potentials in detecting the metabolic perturbations prior to the decline of the left ventricular function.
Methods
Male Sprague-Dawley rats were assigned into two groups, fed a regular chow diet or HFD ad libitum for 10 weeks. We used in vivo imaging of cardiac magnetic resonance (CMR), 18F-FDG PET, and ex vivo nuclear magnetic resonance (NMR) metabolomic analysis for the carbon-13-labeled glucose ([U-13C]Glc) perfused myocardium.
Results
As compared with controls, HFD rats had a higher ejection fraction and a smaller left ventricular end-systolic volume (P < 0.05), with SUVmax of myocardium on 18F-FDG PET significantly increased in 4 weeks (P < 0.005). The [U-13C]Glc probed the increased glucose uptake being metabolized into pyruvate and acetyl-CoA, undergoing oxidative phosphorylation via the tricarboxylic acid (TCA) cycle, and then synthesized into glutamic acid and glutamine, associated with overexpressed LC3B (P < 0.05). Conclusions: HFD-induced IR associated with increased glucose utility undergoing oxidative phosphorylation via the TCA cycle in the myocardium is supported by overexpression of glucose transporter, acetyl-CoA synthase. Noninvasive imaging biomarker has potentials in detecting the metabolic perturbations prior to the decline of the left ventricular function.