title: Oleate protects beta-cells from the toxic effect of palmitate by activating pro-survival pathways of the ER stress response.
abstract: Long-term exposure of beta cells to saturated fatty acids impairs insulin secretion and increases apoptosis. In contrast, unsaturated fatty acids protect beta-cells from the long-term negative effects of saturated fatty acids. We aimed to identify the mechanisms underlying this protective action of unsaturated fatty acids. To address the aim, insulin-secreting MIN6 cells were exposed to palmitate in the absence or presence of oleate and analyzed by using nano-LC MS/MS based proteomic approach. Important findings were validated by using alternative approaches. Proteomic analysis identified 34 proteins differentially expressed in the presence of palmitate compared to control samples. These proteins play a role in insulin processing, mitochondrial function, metabolism of biomolecules, calcium homeostasis, exocytosis, receptor signaling, ER protein folding, antioxidant activity and anti-apoptotic function. When oleate was also present during culture, expression of 15 proteins was different from the expression in the presence of palmitate alone. Most of the proteins affected by oleate are targets of the ER stress response and play a pro-survival role in beta cells such as protein folding and antioxidative defence. We conclude that restoration of pro-survival pathways of the ER stress response is a major mechanism underlying the protective effect of unsaturated fatty acids in beta-cells treated with saturated fatty acids.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Box 571, 75123 Uppsala, Sweden. Electronic address: ernest.sargsyan@mcb.uu.se.
authors.forename: Ernest
authors.initials: E
authors.lastname: Sargsyan
authors.affiliation: Department of Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Artemenko
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Box 571, 75123 Uppsala, Sweden.
authors.forename: Levon
authors.initials: L
authors.lastname: Manukyan
authors.affiliation: Department of Chemistry, Uppsala University, Uppsala, Sweden; SciLifeLab, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Box 571, 75123 Uppsala, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bergsten
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D007340:Insulinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid / Q000008:administration & dosage / Q000378:metabolism; D010084:Oxidation-Reduction; D010168:Palmitates / Q000008:administration & dosage / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage / Q000378:metabolism; D040901:Proteomics; D053719:Tandem Mass Spectrometry
chemical_list: D007328:Insulin; D010168:Palmitates; D020011:Protective Agents; D019301:Oleic Acid
keywords: Apoptosis; ER stress; Insulin secretion; Oleate; Palmitate