title: Mechanistic interplay between ceramide and insulin resistance.
abstract: Recent research adds to a growing body of literature on the essential role of ceramides in glucose homeostasis and insulin signaling, while the mechanistic interplay between various components of ceramide metabolism remains to be quantified. We present an extended model of C16:0 ceramide production through both the de novo synthesis and the salvage pathways. We verify our model with a combination of published models and independent experimental data. In silico experiments of the behavior of ceramide and related bioactive lipids in accordance with the observed transcriptomic changes in obese/diabetic murine macrophages at 5 and 16 weeks support the observation of insulin resistance only at the later phase. Our analysis suggests the pivotal role of ceramide synthase, serine palmitoyltransferase and dihydroceramide desaturase involved in the de novo synthesis and the salvage pathways in influencing insulin resistance versus its regulation.
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Rovereto, Italy.|Department of Mathematics, University of Trento, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Reali
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Rovereto, Italy.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Morine
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Rovereto, Italy.|Department of Mathematics, University of Trento, Italy.
authors.forename: Ozan
authors.initials: O
authors.lastname: Kahramanoğulları
authors.affiliation: Insulin Biology and Counter Regulatory Hormones Dept. R&D Diabetes Division,Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany.
authors.forename: Suryaprakash
authors.initials: S
authors.lastname: Raichur
authors.affiliation: R&D TMED Translational Informatics, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany.
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Schneider
authors.affiliation: R&D TMED Translational Informatics, Sanofi-Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Crowther
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Rovereto, Italy.|Department of Mathematics, University of Trento, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Priami
mesh_terms: D000818:Animals; D002518:Ceramides / Q000378:metabolism*; D003198:Computer Simulation; D007333:Insulin Resistance; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008954:Models, Biological; D013107:Sphingolipids / Q000378:metabolism*; D051049:Sphingosine N-Acyltransferase / Q000378:metabolism
chemical_list: D002518:Ceramides; D013107:Sphingolipids; C584439:CERS6 protein, mouse; D051049:Sphingosine N-Acyltransferase