Exposure of pancreatic beta-cells to long-chain saturated fatty acids (SFA) induces a so-called ER (Endoplasmic Reticulum)-stress that can ultimately lead to cell-death. This process is believed to participate in insulin-deficiency associated with Type 2 Diabetes, via a decrease in beta-cell mass. By contrast, some unsaturated fatty acid species appear less toxic to the cells and can even alleviate SFA-induced ER-stress. In the present study, we took advantage of a simple yeast-based model, which brings together most of the trademarks of lipotoxicity in human cells, to screen fatty acids of various structures for their capacity to counter ER-stress. Here we demonstrate that the tendency of a fatty acid (FFA) to reduce SFA-toxicity depends on a complex conjunction of parameters, including chain length, level of unsaturation, position of the double-bonds and nature of the isomers (cis or trans). Interestingly, potent FFA act as building-blocks for phospholipid synthesis and help to restore an optimal membrane organization, compatible with ER function and normal protein trafficking.CI - (c) 2010 John Wiley & Sons A/S.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|