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Modulation of Lipid‐Induced ER Stress by Fatty Acid Shape
Author(s) -
Deguil Julie,
Pineau Ludovic,
Rowland Snyder Ellen Claire,
Dupont Sébastien,
Beney Laurent,
Gil Adrià,
Frapper Gilles,
Ferreira Thierry
Publication year - 2011
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2010.01150.x
Subject(s) - lipotoxicity , endoplasmic reticulum , unfolded protein response , biology , fatty acid , microbiology and biotechnology , yeast , biochemistry , phospholipid , degree of unsaturation , insulin , membrane , endocrinology , chemistry , insulin resistance , organic chemistry
Exposure of pancreatic β cells to long‐chain saturated fatty acids (SFA) induces a so‐called endoplasmic reticulum (ER) 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 β‐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 free 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.