Document Detail

Saturated long-chain fatty acids activate inflammatory signaling in astrocytes.
MedLine Citation:
PMID:  22248073     Owner:  NLM     Status:  MEDLINE    
This study describes the effects of long-chain fatty acids on inflammatory signaling in cultured astrocytes. Data show that the saturated fatty acid palmitic acid, as well as lauric acid and stearic acid, trigger the release of TNFα and IL-6 from astrocytes. Unsaturated fatty acids were unable to induce cytokine release from cultured astrocytes. Furthermore, the effects of palmitic acid on cytokine release require Toll-like receptor 4 rather than CD36 or Toll-like receptor 2, and do not depend on palmitic acid metabolism to palmitoyl-CoA. Inhibitor studies revealed that pharmacologic inhibition of p38 or p42/44 MAPK pathways prevents the pro-inflammatory effects of palmitic acid, whereas JNK and PI3K inhibition does not affect cytokine release. Depletion of microglia from primary astrocyte cultures using the lysosomotropic agent l-leucine methyl ester revealed that the ability of palmitic acid to trigger cytokine release is not dependent on the presence of microglia. Finally, data show that the essential ω-3 fatty acid docosahexaenoic acid acts in a dose-dependent manner to prevent the actions of palmitic acid on inflammatory signaling in astrocytes. Collectively, these data demonstrate the ability of saturated fatty acids to induce astrocyte inflammation in vitro. These data thus raise the possibility that high levels of circulating saturated fatty acids could cause reactive gliosis and brain inflammation in vivo, and could potentially participate in the reported adverse neurologic consequences of obesity and metabolic syndrome.
Sunita Gupta; Alecia G Knight; Shruti Gupta; Jeffrey N Keller; Annadora J Bruce-Keller
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-02-06
Journal Detail:
Title:  Journal of neurochemistry     Volume:  120     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-07     Completed Date:  2012-06-01     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1060-71     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
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MeSH Terms
Animals, Newborn
Astrocytes / drug effects*
Brain / cytology
Cells, Cultured
Cytokines / metabolism*
Dose-Response Relationship, Drug
Drug Interactions
Enzyme Inhibitors / pharmacology
Enzyme-Linked Immunosorbent Assay
Fatty Acids / metabolism,  pharmacology*
Gene Expression Regulation / drug effects
Oleic Acid / pharmacology
Palmitic Acid / pharmacology
Rats, Sprague-Dawley
Signal Transduction / drug effects*
Toll-Like Receptor 2 / metabolism
Toll-Like Receptor 4 / metabolism
Grant Support
Reg. No./Substance:
0/Cytokines; 0/Enzyme Inhibitors; 0/Fatty Acids; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 112-80-1/Oleic Acid; 57-10-3/Palmitic Acid

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