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Exposure to the Saturated Free Fatty Acid Palmitate AltersBV-2 Microglia Inflammatory Response
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0002-6668-1094
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0002-1007-747X
Stockholm University, Faculty of Science, Department of Neurochemistry.
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2013 (English)In: Journal of Molecular Neuroscience, ISSN 0895-8696, E-ISSN 1559-1166, Vol. 51, no 3, 805-812 p.Article in journal (Refereed) Published
Abstract [en]

Elevated levels of free fatty acids (FFAs) in plasma and increased incidence of chronic systemic inflammation are associated with obesity. In the brain, activated microglia are believed to play different roles during inflammation that may either be neuroprotective or promote neurodegeneration. Here, we have investigated the effects of FFAs on microglial response to inflammatory stimuli. Our results indicate that the saturated FFA palmitate on its own induces alternative activation of BV-2 microglia cells. Further, pre-exposure to palmitate changed the response of microglia to lipopolysaccharide (LPS). We show that palmitate affects the mRNA levels of the pro-inflammatory cytokines interleukin-1β and interleukin-6. The transcription factor CCAAT/enhancer-binding protein δ is also affected by pre-exposure to palmitate. Furthermore, the phagocytic activity of microglia was investigated using fluorescent beads. By analyzing the bead uptake by fluorescence-activated cell sorting, we found that palmitate alone, as well as together with LPS, stimulated the phagocytic activity of microglia. Taken together, our results suggest that exposure of microglia to increased levels of free fatty acids may alter the consequences of classical inflammatory stimuli.

Place, publisher, year, edition, pages
2013. Vol. 51, no 3, 805-812 p.
National Category
Biochemistry and Molecular Biology Neurosciences
Identifiers
URN: urn:nbn:se:su:diva-95103DOI: 10.1007/s12031-013-0068-7ISI: 000325710500021OAI: oai:DiVA.org:su-95103DiVA: diva2:658298
Available from: 2013-10-21 Created: 2013-10-21 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Neuroinflammation in Alzheimer’s disease and obesity
Open this publication in new window or tab >>Neuroinflammation in Alzheimer’s disease and obesity
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Alzheimer’s disease (AD) and obesity are both major problems in the western world. Although they may appear to have little in common at first glance, they are both characterized by chronic inflammation. Exactly how inflammation affects these disorders is far from clear. Microglia, the resident immune cells of the brain, can take on different phenotypes in response to inflammatory stimuli. They can become classically or alternatively activated, where they secrete pro- or anti-inflammatory cytokines respectively. The inflammatory response is to a large part regulated by transcription factors, such as C/EBPδ, which regulate gene expression. The aim of this thesis was to investigate 1) effects of the Alzheimer’s related peptide amyloid-β (Aβ) on C/EBPδ in astrocytes and microglia during inflammatory conditions, 2) how microglia is affected by elevated levels of free fatty acids (FFAs) occurring in obesity and 3) possible cellular sources of the neuroprotective peptide GLP-1 in the brain. In paper I we found that IL-1β-induced C/EBPδ appears to be blocked by Aβ fibrils but not Aβ oligomers in mixed glial cells. In paper II we found that the decreased levels of C/EBPδ were limited to astrocytes under inflammatory conditions and that there was no blocking of IL-1β-induced C/EBPδ in microglia. In paper III we found that the FFA palmitate induces an alternative activation in microglia with no effect on the expression of C/EBPδ or the pro-inflammatory cytokines TNF-α, IL-1β and IL-6. However, pre-exposure to palmitate potentiated microglia phagocytosis and changed the mRNA expression profile of some pro-inflammatory cytokines in response to inflammatory stimuli. In paper IV we found microglia to be a novel source of secreted GLP-1. Further, we found that the GLP-1 secretion could be decreased by inflammatory stimuli. In summary, the inflammatory response of C/EBPδ in AD appears to be disturbed. In addition, palmitate affects the response to inflammatory stimuli in microglia.

Place, publisher, year, edition, pages
Stockholm: Department of Neurochemistry, Stockholm University, 2013. 56 p.
Keyword
Alzheimer's disease, obesity, neuroinflammation
National Category
Natural Sciences
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
urn:nbn:se:su:diva-95104 (URN)978-91-7447-731-3 (ISBN)
Public defence
2013-11-22, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 13:00 (English)
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Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 2: Manuscript.

Available from: 2013-10-31 Created: 2013-10-21 Last updated: 2015-03-16Bibliographically approved

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