Paying at the Pump

Abstract

Cardiac steatosis, or the abnormal accumulation of myocardial lipid, has recently emerged as an identifiable feature of insulin-resistant states including obesity and type 2 diabetes mellitus.1 Although the presence of increased myocardial lipid has been associated with both systolic and diastolic dysfunction in human and animal studies, it remains unclear whether accumulated lipid species are intrinsically pathological (the “lipotoxicity” hypothesis) or simply a marker of a fundamental derangement in cellular metabolism.2 It has been hypothesized that in insulin-resistant states, cellular fatty acid uptake exceeds mitochondrial oxidative capacity, leading to the generation of cytotoxic lipid metabolites that affect cardiac function through a variety of potential mechanisms.2 Indeed, many of the mouse models that recapitulate the diabetic phenotype and elicit myocardial steatosis also alter cellular systems that regulate lipid metabolism and energy substrate utilization.3–5 Article see p 710 It is relatively simple to measure myocardial lipid in animal models because cardiac tissue is readily available ex vivo for histological processing. In vivo measurements from a beating heart and breathing animal, although much more challenging, are possible with the application of image-guided proton magnetic resonance spectroscopy (MRS).6 Proton MRS is similar to MRI in that protons, principally contained in water and fat in biological tissue, generate a measureable nuclear magnetic resonance (NMR) signal when placed in a strong external magnetic field and exposed to tuned radiofrequency energy. In MRI, the NMR signals from all protons irrespective of their chemical environment are summed to generate an intensity that is localized in space by the application of multiple magnetic field gradients. In MRS, the various populations of protons can be separated into a signal intensity spectrum by differences in their intrinsic resonance signatures. In this way, chemical species' concentrations can be determined noninvasively from a volume of tissue …