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Oleate increase neutral lipid accumulation, cellular respiration and rescues palmitate-exposed GLP-1 secreting cells by reducing ceramide-induced ROS
Sodertalje Hosp, Dept Res, STS Biovat, SE-15286 Sodertalje, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
Sodertalje Hosp, Dept Res, STS Biovat, SE-15286 Sodertalje, Sweden.
Sodertalje Hosp, Dept Res, STS Biovat, SE-15286 Sodertalje, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
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2019 (English)In: Biochimie, ISSN 0300-9084, E-ISSN 1638-6183, Vol. 159, p. 23-35Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER , 2019. Vol. 159, p. 23-35
Keywords [en]
Type 2 diabetes, Unsaturated/saturated fatty acids, GLP-1 secretion, Lipotoxicity, Lipoprotection, Ceramide
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-381113DOI: 10.1016/j.biochi.2018.11.017ISI: 000461698100004PubMedID: 30513370OAI: oai:DiVA.org:uu-381113DiVA, id: diva2:1302437
Funder
Tore Nilsons Stiftelse för medicinsk forskningFredrik och Ingrid Thurings StiftelseAvailable from: 2019-04-04 Created: 2019-04-04 Last updated: 2019-04-04Bibliographically approved

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Kristinsson, HjaltiBergsten, Peter

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