Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease

Area of Science:

• Cardiovascular Science
• Metabolomics
• Obesity Research

Background:

• Obesity is a known risk factor for cardiovascular disease.
• The specific role of adipose tissue (AT) metabolic dysregulation in cardiovascular risk remains unclear.

Purpose of the Study:

• To investigate the influence of adipose tissue metabolome dysregulation on vascular redox signaling and cardiovascular outcomes.
• To identify specific metabolites involved in this process.

Main Methods:

• Compared metabolite secretion from thoracic AT (ThAT) and subcutaneous AT in obese patients with atherosclerosis.
• Linked identified metabolites to vascular redox signaling in patients undergoing coronary bypass surgery.
• Explored mechanisms in human aortic endothelial cells and validated clinical impact against hard endpoints.

Main Results:

• Thoracic AT volume correlated with arterial oxidative stress and showed distinct sphingolipid secretion, notably C16:0-ceramide.
• High ThAT ceramide secretion was linked to reduced nitric oxide bioavailability and increased superoxide production.
• Plasma C16:0-ceramide levels positively correlated with inflammation and predicted increased cardiac mortality.
• Liraglutide treatment in obese patients reduced plasma ceramide levels.

Conclusions:

• Adipose tissue-derived ceramides are identified as modifiable regulators of vascular redox state in obesity.
• These ceramides directly influence cardiac mortality in advanced atherosclerosis.
• Targeting ceramides may offer a therapeutic strategy for obesity-related cardiovascular complications.