Dihydroceramide desaturase 1, the gatekeeper of ceramide induced lipotoxicity

• Dihydroceramides are the precursors of ceramides in the de novo biosynthesis pathway.
• Dihydroceramides emerge as important bioactive molecules.
• DEGS1 expression and activity are differentially regulated by physiological and pathophysiological stimuli.

The pathogenic relevance of sphingolipid metabolism is increasingly being recognised. Here we elaborate on a new player within the sphingolipid field: the degs1 enzyme, a recently discovered enzyme that catalyses the final step in the de novo biosynthesis of ceramides controlling the step from dihydroceramides to ceramides. Here, we describe its function and dysregulation by factors such as oxidative stress, hypoxia and inflammation and provide evidence indicating that dihydroceramides constitute a biologically active molecule from the sphingolipid family with certain differential characteristics with respect to its delta-4 unsaturated counterparts, the ceramides. Finally we present pathophysiological scenarios characterised by specific increases in dihydroceramide that challenge the concept that “all ceramides species are the same”. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics.