Overnutrition, inflammation, and genetic aberrations promote the accumulation of sphingolipids such as ceramides, which alter metabolic programs and induce apoptosis in a wide range of cell types. In humans, serum ceramides are biomarkers of diabetes and major adverse cardiac events, and clinics have started measuring circulating ceramides as markers of disease risk. In rodents, inhibiting ceramide biosynthesis ameliorates diabetes, steatohepatitis, kidney injury, and heart failure. The author will discuss the evolution of this pathway as a signal of lipid excess and the therapeutic potential of a new approach, involving the elimination of a double bond, that inactivates ceramides and ameliorates cardiometabolic pathologies.
The author is a co-founder and shareholder of Centaurus Therapeutics, inc.