Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans.

Our understanding of the cellular mechanisms by which animals regulate their response to starvation is limited despite the strong relevance of the problem to major human health issues. The L1 diapause of Caenorhabditis elegans, where first-stage larvae arrest in response to a food-less environment, is an excellent system to study this mechanism. We found through genetic manipulation and lipid analysis that ceramide biosynthesis, particularly those with longer fatty acid side chains, critically impacts animal survival during L1 diapause. Genetic interaction analysis suggests that ceramide may act in both Insulin-IGF-1 signaling (IIS)-dependent and IIS-independent pathways to affect starvation survival. Genetic and expression analyses indicate that ceramide is required for maintaining the proper expression of previously characterized starvation responsive genes, genes that are regulated by the IIS pathway and tumor suppressor Rb, and genes responsive to pathogen. These findings provide an important insight into the roles of sphingolipid metabolism in not only starvation response, but also aging and food-response related human health problems.