Talk by Jens Brüning
Title: "Targeting specific ceramide synthases in metabolic disorders"
Occasion: SFB Seminar
Host: Florian Fröhlich
Start: 28.04.2022 - 16:15
Location: CellNanOs 38/201
About the speaker: Jens C. Brüning heads the group Neuronal Control of Metabolism at the Max Planck Institute of Metabolism Research in Köln.
Abstract of the talk: Ceramide accumulation in non-adipose tissues has been identified as a negative regulator of glucose tolerance and lipid metabolism. Ceramides are formed by the N-acylation of a sphingoid long chain base and are central to sphingolipid metabolism. Individual (dihydro-) ceramide synthases (CerS)s generate ceramides of different acyl-chain lengths (C14:0-C30:0). Only recently through the generation and characterization of different CerS knockout mice, the specific role of distinct CerSs and their ceramide products has begun to be elucidated. We have demonstrated that in obesity specifically CerS6-dependently generated C16:0 ceramides are responsible for the inhibition of β-oxidation in liver and brown adipose tissue. Strikingly, lack of CerS5, which also catalyzes the formation of C16:0 ceramides, fails to protect from obesity or obesity-associated insulin resistance. Through the identification of distinct proteins which interact selective with C16:0 ceramides generated by CerS6, but not with CerS5, we reveal a novel differential role for the molecular basis, how the same ceramide class exerts distinct biological functions, dependent on the CerS isoform it was formed by. In contrast, CerS1-dependently generated C18:0 ceramides, and not CerS6-dependently formed C16:0 ceramides represent critical mediators of obesity-associated insulin resistance in skeletal muscle. Collectively our experiments validate specific CerS-proteins rather than inhibition of global ceramide synthesis as novel targets for the treatment of obesity and obesity-associated insulin resistance.