Impact of Nutrition on Sphingolipid-Regulated Physiology: A Review

Sphingolipids (SLs) are a very diverse group of lipids already described by German physician Johann Thudichum in 1884. The name of these lipids originates from their (at the time) enigmatic nature and lack of knowledge about their cellular function, which was compared to the creature sphinx in Greek mythology. Today we know that SLs play an important role in a plethora of physiological and cellular processes, including tissue development, growth regulation, apoptosis, adhesion, cell migration, cell senescence, receptor signaling, and hormonal effects and are associated with multiple pathological processes in many different disease contexts. In addition to roles for specific SLs in developmental processes, their critical role in causing and preventing metabolic diseases, including cardiovascular disease, obesity, and diabetes during adulthood, has been uncovered through targeted genetic manipulation, lipidomics, and advanced biochemical analyses such as lipid-protein interactomics. Notably, in the context of maternal and paternal effects on offspring and their risk for metabolic disease, there is a gap in our knowledge regarding SLs in transgenerational disease mechanisms. This review summarizes our knowledge on SL metabolism and cellular roles in health and disease, while focusing on the current knowledge of dietary effects on SL-controlled metabolism of adults and their developing offspring.