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Bhagirath Chaurasia Department of Nutrition and Integrative Physiology, University of Utah gives a talk entiled: "Ceramide induced lipotoxicity in metabolic diseases"
07.11.2019 |
| Dato | man 11 nov |
| Tid | 14:15 — 15:00 |
| Sted | Steno Diabetes Centre, Hedeager 3, 8200 Aarhus N, the lecture theatre at floor 2. |
The ectopic deposition of lipid molecules in tissues not suited for fat storage drives the tissue
dysfunction that underlies diabetes and heart disease. Of the numerous lipid subtypes that
accumulate, ceramides and dihydroceramides, show particularly tight associations with these
metabolic disorders. Indeed, clinics recently began quantifying serum ceramides as diagnostic
measures of risk for major adverse cardiac events. Studies in rodents further suggest that these
sphingolipids play causative roles in the pathologies. Ceramides further serve as signals of lipid
overload, altering cellular metabolism and rigidifying membranes in order to prevent
dissolution of lipid bilayers that could result from the deluge of excess, detergent-like fatty
acids. These actions, when prolonged, elicit the tissue dysfunction (e.g. insulin resistance,
decreased mitochondrial efficiency, enhanced triglyceride synthesis, apoptosis, fibrosis, etc.)
that underlies diabetes and heart disease. Attempts to develop safe therapeutics targeting
these enzymes have been problematic, however, owing to negative consequences of global
sphingolipid depletion. The presentation will review the history of research on these enigmatic
molecules, exploring (a) their mechanism of action, (b) the evolutionary pressures that gave
them their unique attributes, and (c) the potential of ceramide-reduction therapies as
treatments for cardiometabolic disease.