Physiologic Plasticity of Intramyocardial Lipid Storage

Background

Obesity is a well known risk factor for the development of glucose intolerance, type 2 diabetes mellitus and, consequently, diabetic complications like cardiovascular disease. Importantly, obesity is not only associated with lipid accumulation in adipose tissue (orthotopic fat deposition), but also in non-adipose tissues (ectopic fat deposition). Clinical studies have repetitively shown that muscular and hepatic lipid accumulation as well as elevated visceral adipose tissue is associated with the development of central and peripheral insulin resistance. In addition, recent data from animal studies show increasing evidence that two other organs, the heart and the pancreas, may also be involved in the pathophysiological processes of reduced insulin sensitivity. While reduced insulin secretion in the course of type 2 diabetes has been well documented, the importance of pancreatic fat deposition as an early step in this process has only recently been suggested based on animal models. Conversely, ischemic heart disease is one of the most dangerous complications of diabetes mellitus, its prevention thereby being a cornerstone of current diabetes management. Recent data suggest that changes in the lipid metabolism of the heart and associated epi- and myocardial lipid deposition may be earliest signs of diabetic cardiopathy.

Magnetic-Resonance-Imaging (MRI) and -Spectroscopy (MRS) are among the most versatile methods for non-invasive studies of human tissue and/or metabolism in vivo and in situ. The excellent soft tissue contrast of MRI has already led to the implementation of this method for the assessment of whole body lipid accumulation, whereas MRS has successfully been applied to study lipid metabolism of skeletal muscle and liver. The extended application of this method towards heart and pancreas will allow a comprehensive investigation of orthotopic and ectopic fat deposition in humans and its association with the development of insulin resistance and diabetes mellitus.

The methodological part of the study will focus on the physiologic plasticity of cardiac lipids in order to assess:

i) methodological reproducibility ii) intra-individual physiological reproducibility by measuring day-to-day variations as well as variations during the day.

Objective

i) Adapting and optimizing the single-voxel MRS sequence that is currently used for muscle and liver, such that respiratory and cardiac double-triggering enables spectroscopy of the cardiac muscle.

ii) Validate the methodology under different standardized physiologic conditions.

Methods

Cardiac lipids are determined during five independent MR-examinations distributed over two days separated by one or two weeks. Both days included a measurement in the morning after an overnight fast (>8h) and one in the afternoon (8h after breakfast, 3.5h after lunch). To determine methodological reproducibility, the afternoon measurement was repeated on one of the two days (1h break). Preparation of the volunteers included perpetuation of their normal diet, but restricted physical activity for two preceding days. Cardiac lipids were determined by single-voxel MR-Spectroscopy.