Paying at the Pump

Abstract

C ardiac 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][4][5] Article see p 710It 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 imageguided 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 with a high degree of accuracy and reproducibility. Specifically, intracellular lipids can be quantified by determining the total spectral peak areas corresponding to the methylene (CH 2 , seen at approximately 1.4 parts per million) and methyl (CH 3 , seen at approximately 0.8 to 1.0 parts per million) side chains expressed as a fraction of the total water signal (at 4.7 parts per million). 7 Although cardiac proton MRS studies offer tremendous potential for clinical and research applications, the technique remains challenging to perform and interpret. 8 Furthermore, as opposed to MRI-based techniques such as late gadolinium enhancement, no clinical question has been identified that cardiac MRS can uniquely answer to affect patient treatment, limiting its widespread adaptation. This is in contrast to the research applications of proton MRS to assess myocardial lipid or phosphorus MRS to quantify cardiac high-energy phosphates. 9,10 A few centers have developed expertise in ...

Fasting-Induced Myocardial Lipid Accumulation in Long-Chain Acyl-CoA Dehydrogenase Knockout Mice Is Accompanied by Impaired Left Ventricular Function

“…Remarkably, the lipid signal as detected by 1 H-MRS in this study was not exclusively attributable to TG. 14,15 The purpose of this animal study is to examine, for the first time, changes in cardiac morphology, function, and TG storage as a consequence of FAO deficiency. MRI and 1 H-MRS were applied in vivo in long-chain acyl-CoA dehydrogenase (LCAD) knockout (KO) mice and wild-type (WT) C57BL/6 mice.…”