Increased Myocardial Uptake of Dietary Fatty Acids Linked to Cardiac Dysfunction in Glucose-Intolerant Humans

Abstract

Impaired cardiac systolic and diastolic function has been observed in preclinical models and in subjects with type 2 diabetes. Using a recently validated positron emission tomography (PET) imaging method with 14(R,S)-[18F]-fluoro-6-thia-heptadecanoic acid to quantify organ-specific dietary fatty acid partitioning, we demonstrate in this study that overweight and obese subjects with impaired glucose tolerance (IGT+) display significant increase in fractional myocardial dietary fatty acid uptake over the first 6 h postprandial compared with control individuals (IGT−). Measured by [11C]acetate with PET, IGT+ subjects have a significant increase in myocardial oxidative index. IGT+ subjects have significantly reduced left ventricular stroke volume and ejection fraction (LVEF) and tend to display impaired diastolic function, as assessed by PET ventriculography. We demonstrate an inverse relationship between increased myocardial dietary fatty acid partitioning and LVEF. Fractional dietary fatty acid uptake is reduced in subcutaneous abdominal and visceral adipose tissues in IGT+ directly associated with central obesity. Fractional dietary fatty acid uptake in skeletal muscles or liver is, however, similar in IGT+ versus IGT−. The current study demonstrates, for the first time, that excessive myocardial partitioning of dietary fatty acids occurs in prediabetic individuals and is associated with early impairment of left ventricular function and increased myocardial oxidative metabolism.