Ceramides in non-communicable diseases: pathways, nutritional modulation, and therapeutic opportunities

Ceramides are sphingolipids formed from fatty acids linked to sphingosine and an amide, which are involved in cellular pathways such as apoptosis, fibrosis, oxidative stress, and inflammation. Six distinct fatty acyl selective ceramide synthases (CerS) produce ceramides. This specific enzymatic modulation can either increase or reduce the production of specific ceramides, which can have either adverse or protective effects, suggesting that enzymatic modulation may serve as a tool for innovative therapy. Specifically, modulation of glucosylceramide synthase, sphingomyelinase, or ceramidase can reverse the generation of potentially apoptotic ceramides, similar to how inhibition of serine palmitoyltransferase or ceramide synthases may be significant in inflammatory conditions by decreasing the generation of inflammatory ceramides. In this context, the modulation of plasma ceramides may represent a protective factor for chronic non-communicable diseases (NCDs), such as cardiovascular diseases, type 2 diabetes, and chronic kidney disease. Previous studies indicate that dietary fat and protein intake influence plasma sphingolipid levels. Therefore, this review aims to discuss the effects of ceramide on patients with NCDs, providing an overview of the influence of nutrition on ceramide levels and outlining future perspectives.