Phospholipid and Sphingolipid Signaling in Drosophila

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

Ceramide kinases are involved in the generation of ceramide 1-phosphate from ceramide and thus regulate Ceramide mediated biological functions. In our previous studies we had identified genetic interactors of ceramide kinase. One of the enzymes unregulated in a ceramide kinase mutant was a lipase secreted in the gut. In a study published recently we demonstrate that that the Drosophila secretory lipase, Vaha (CG8093), is synthesized in the midgut and moves to the brain where it concentrates in the insulin-producing cells in a process requiring Lipid Transfer Particle, a lipoprotein originating in the fat body. In response to dietary fat, Vaha stimulates insulin-like peptide release (ILP), and Vaha deficiency results in reduced circulatory ILP and diabetic features including hyperglycemia and hyperlipidemia. Our findings suggest Vaha functions as a diacylglycerol lipase physiologically, by being a molecular link between dietary fat and lipid amplified insulin secretion in a gut-brain axis. We are evaluating ways to translate our findings to human relevance with respect to incretin like effects of various peptides and proteins in regulating insulin secretion. Additionally, We are continuing to explore the implications of our findings in human contexts by exploring other genes impacted in the ceramide kinase mutants.