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Lipid‐mediated ER stress
Author(s) -
Schaffer Jean E
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.410.1
Subject(s) - lipotoxicity , unfolded protein response , endoplasmic reticulum , microbiology and biotechnology , biology , pathogenesis , oxidative stress , adipose tissue , programmed cell death , lipid droplet , lipid signaling , lipid metabolism , apoptosis , diabetes mellitus , endocrinology , inflammation , insulin resistance , biochemistry , immunology
Cell dysfunction and cell death induced by lipid accumulation in non‐adipose tissues, or lipotoxicity, may contribute to the pathogenesis of diabetes and obesity. We have investigated this pathophysiological response in a cell culture model in which growth media is supplemented with excess palmitic acid. Biochemical studies reveal that palmitate is rapidly incorporated into endoplasmic reticulum membranes (ER), leading to membrane remodeling that results in a breach of ER structure and function. Palmitate also induces oxidative and ER stress. In complementary genetic studies in mammalian fibroblasts, we are beginning to identify genes critical for lipotoxic cell death. These findings are being translated into murine models of lipotoxicity in which lipid accumulation causes organ dysfunction. By combining in vitro identification of molecular targets and signaling pathways with in vivo models of lipotoxic disease, our goal is to provide insight into the pathogenesis of common metabolic diseases.