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Reference: Deguil J, et al. (2011) Modulation of Lipid-Induced ER Stress by Fatty Acid Shape. Traffic 12(3):349-362

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Abstract

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.

Reference Type
Journal Article
Authors
Deguil J, Pineau L, Rowland Snyder EC, Dupont S, Beney L, Gil A, Frapper G, Ferreira T
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