Towards understanding regulation of energy homeostasis by ceramide synthases

Energy homeostasis and growth require the coordinated regulation of lipid metabolism. The underlying molecular mechanisms are poorly understood. We are interested in identifying key regulators of lipid homeostasis and their functional mechanism. Recently, we identified the schlank gene as a major regulator of lipid homeostasis in Drosophila. Schlank encodes a conserved member of the Lass/CerS family of ceramide synthases , which contain a catalytic Lag1 motif and a homeobox transcription factor domain. Schlank mutant larvae, show decreased levels of sphingolipids and depleted fat stores due to an upregulation of triacylglycerol lipases and a downregulation of SREBP-dependent fatty acid synthesis. In addition, we have demonstrated that mammalian members of the conserved Lass/CerS family had also effects on lipid homeostasis. Therefore, we are currently interested to find how members of this family e.g., schlank may act as regulators coordinating cellular and organismic lipid homeostasis in animals mechanistically. We now address these issues by using a combination of genetics, biochemistry and integrative physiology.