Early Imaging Biomarker of Myocardial Glucose Adaptations in High-Fat-Diet-Induced Insulin Resistance Model by Using 18F-FDG PET and [U-13C]glucose Nuclear Magnetic Resonance Tracer

Abstract

Background. High-fat diet (HFD) induces systemic insulin resistance leading to myocardial dysfunction. We aim to characterize the early adaptations of myocardial glucose utility to HFD-induced insulin resistance. 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.