Oleate increase neutral lipid accumulation, cellular respiration and rescues palmitate-exposed GLP-1 secreting cells by reducing ceramide-induced ROS
| Autor: | Peter Bergsten, Ketan Thombare, Camilla Krizhanovskii, Masood Aryapoor, Hjalti Kristinsson, Stelia Ntika |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Ceramide Cellular respiration Hyperlipidemias Ceramides Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound Glucagon-Like Peptide 1 Cell Line Tumor Free fatty acid receptor 1 Ceramide kinase Respiration Animals Humans Secretion 030102 biochemistry & molecular biology Chemistry food and beverages General Medicine Cell biology 030104 developmental biology Lipotoxicity Reactive Oxygen Species Intracellular Oleic Acid |
| Zdroj: | Biochimie. 159:23-35 |
| ISSN: | 0300-9084 |
| DOI: | 10.1016/j.biochi.2018.11.017 |
| Popis: | Background Fatty acids (FAs), and especially monounsaturated FAs (MUFAs) stimulate GLP-1 release. However, lipotoxicity is indicated in GLP-1 secreting cells following long-term exposure to elevated levels of saturated FAs (SFAs) in vivo and in vitro, where in vitro studies indicate that cosupplementation with MUFAs confers lipoprotection. SFAs and MUFAs differentially affect the fate of cells in ways that depend on the cell type, concentration and ratio of the FAs. The present study was designed to further elucidate the mechanisms underlying the effects of SFAs/MUFAs on GLP-1-producing cells in terms of lipotoxicity/lipoprotection and GLP-1 secretion. Methods Cultured GLP-1 secreting cells were exposed to hyperlipidemia simulated by SFA-albumin complexes where the molar ratio was 2:1. The cellular response to simulated hyperlipidemia was assessed in the presence/absence of MUFA cosupplementation by determining intracellular ceramide, ROS, neutral lipid accumulation, and cellular respiration. The role for cellular respiration in GLP-1 secretion in response to SFAs/MUFAs was assessed. Results Generation of intracellular ceramide mediate a detrimental increased in ROS production following long term exposure to SFAs in GLP-1-secreting cells. Cosupplementation with MUFAs increases cellular respiration, triglyceride synthesis, and the expression of ceramide kinase, while reducing ceramide synthesis and attenuating ROS production, caspase-3 activity and DNA fragmentation. Further, acute secretory effects of unsaturated FAs are independent of FAO, but mediated by a FFAR1 induced increase in cellular respiration. Conclusion This study demonstrates novel data supporting effects of MUFAs on the ceramide biosynthetic pathway, triglyceride storage respiration and secretion in GLP-1 secreting cells. These findings may be of value for nutritional interventions, as well as for identification of novel targets, to help preserve L-cell mass and potentiate GLP-1 secretion in diabesity. |
| Databáze: | OpenAIRE |
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