Ceramide synthase homeodomain regulates lipid homeostasis

What is it about?

Misregulation of lipid homeostasis is often associated with pathogenic changes such as cancer, cardiovascular diseases, neurodegeneration or diabetes. The highly conserved Ceramide synthase (CerS) proteins generating (dihydro) ceramide and the metabolites produced thereof have an important role in regulating lipid homeostasis. We now found a mechanism that explains the dual functions of Drosophila CerS Schlank in ceramide synthesis and body fat regulation. Schlank contains a catalytic lag1p motif and, like many CerS in other species, a homeodomain, which is often found in transcription factor proteins. André showed that the homeodomain of Schlank is involved in the regulation of lipid metabolism independent of the catalytic lag1p motif. The fact that most mammalian CerS contain a homeodomain suggests a regulatory role for these homeodomains too. Whether or not this is true is yet to be determined.

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Why is it important?

We suggest an alternative route of fat storage modulation mediated via the CerS homeodomain, besides the ceramide synthase function yielding ceramide and derived metabolites. The mechanism outlined here could have clinical implications in diseases associated with ceramide such as diabetes and obesity.