Ceramide Levels in Adipose Tissue Stabilize with Liraglutide, Study Shows

Elevated levels of the lipid ceramide, which increase mortality risk for cardiovascular disease, were held in check by liraglutide, according to new study results.

“We reveal for the first time the role that the ceramides play as messengers that bring about the damaging effect on blood vessels that we see in obesity,” lead investigator Charalambos Antoniades said in a press release. “This presents unique opportunities for the improved diagnosis and treatment of cardiovascular disease.”

The authors, publishing in the Journal of the American College of Cardiology sought to examine the role of dysregulation in the adipose tissue metabolome on vascular redox signaling and cardiovascular outcomes.

The study included 633 patients with atherosclerosis undergoing coronary artery bypass surgery. The researchers conducted a screen for metabolites differentially secreted by thoracic adipose tissue (ThAT) and subcutaneous adipose tissue in 48 obese patients with atherosclerosis, and then linked them with dysregulated vascular redox signaling and cardiovascular outcomes.

Ceramide Linked with Increased Mortality

The results indicated that high plasma C16:0-ceramide and its glycosylated derivative were independently associated with an increased risk for cardiovascular mortality (adjusted HR: 1.394; 95% CI, 1.030 to 1.886). These results were consistent with previous research from other groups.

“Because ThAT volume was associated significantly with arterial oxidative stress, there were significant differences in sphingolipid secretion between ThAT and subcutaneous AT, with C16:0-ceramide and derivatives being the most abundant species released within adipocyte-derived extracellular vesicles,” they wrote in their results. “High ThAT sphingolipid secretion was significantly associated with reduced endothelial nitric oxide bioavailability and increased superoxide generated in human vessels.”

Co-author Antonio Checa, a researcher at Karolinska Institutet, said in a press release that the “results suggest that it could be worth incorporating the measurement of different kinds of sphingolipids, both in their original form as well as the glycosylated variants, to better gauge the risk of the occurrence of a fatal cardiovascular event,” says co-author Antonio Checa, researcher at Karolinska Institutet who developed the sphingolipid platform and conducted the analyses.”

Can Ceramide Levels Be Reduced?

In another part of the study, the authors examined whether high ceramide levels in the blood can be reduced. They looked at 32 volunteers on a low-carbohydrate diet for eight weeks, and then split them into two groups (one assigned liraglutide and one assigned placebo). The groups continued with the diet for another 44 weeks. At one year, ceramide levels had increased in the placebo group, but had remained stable in the liraglutide group.

“Understanding the link between obesity and cardiovascular diseases is important and can lead the way to the development of new therapies,” principal investigator docent Craig Wheelock, of the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, said in a press release. “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. In addition, all tissue is not equal, and the type of fat is clearly important in determining the observed biological function.”