Oleate protects beta-cells from the toxic effect of palmitate by activating pro-survival pathways of the ER stress response
2016 (English)In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1861, no 9, 1151-1160 p.Article in journal (Refereed) Published
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 MINE 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.
Place, publisher, year, edition, pages
2016. Vol. 1861, no 9, 1151-1160 p.
Palmitate, Oleate, Insulin secretion, Apoptosis, ER stress
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-304161DOI: 10.1016/j.bbalip.2016.06.012ISI: 000381533700021PubMedID: 27344025OAI: oai:DiVA.org:uu-304161DiVA: diva2:1014880
FunderEU, FP7, Seventh Framework Programme, 279153Swedish Diabetes Association, DIA 2013-043Swedish Research Council, 621-2011-4423