Researchers at the Karolinska Institutet, University of Oxford and University of Copenhagen have shown that elevated levels of lipids known as ceramides can be associated with a ten-fold higher risk of death from cardiovascular disease. Treatment with liraglutide could keep the ceramide levels in check, compared with placebo. The results have been published in the Journal of the American College of Cardiology.
Fat has traditionally been seen as simply storage tissue, but in recent years it has been shown to be a "biochemical laboratory" capable of producing signaling molecules that exert potent biological functions.
Applying a mass-spectrometry method called metabolomics, the Wheelock Laboratory was able to measure levels of multiple metabolites secreted by two kinds of human fat tissue.
The fat that accumulated around the heart in obese individuals secreted different metabolites relative to subcutaneous fat. Notably, thoracic adipose tissue (which surrounds the heart) from obese individuals secreted higher levels of ceramides, a kind of lipid that belongs to the sphingolipid family. In particular, elevated levels were observed of a lipid variant called C16:0-ceramide, which is based on palmitic acid—a saturated fat consisting of 16 carbon atoms. Ceramides are found in high levels in cell membranes and are also important signaling molecules.
The researchers were also able to show that ceramides secreted from adipose tissue damaged human blood vessels by initiating a process called oxidative stress, which can eventually lead to heart attacks and stroke.
"These results show emphatically that fat is not just energy-storage tissue but also a source of important bioactive molecules that can have powerful immunomodulatory functions," Wheelock says. "In addition, all tissue is not equal, and the type of fat is clearly important in determining the observed biological function."