Document Detail


Omega-3 fatty acid deficiency increases constitutive pro-inflammatory cytokine production in rats: relationship with central serotonin turnover.
MedLine Citation:
PMID:  20817496     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Omega-3 (n-3) fatty acid deficiency, elevated inflammatory signaling, and central serotonin (5-HT) turnover have separately been implicated in the pathophysiology of major depressive disorder (MDD). In the present study we investigated the interrelationship between n-3 fatty acid status, pro-inflammatory signaling activity, and central 5-HT turnover in vivo. Rats were fed diets with or without the n-3 fatty acid precursor α-linolenic acid (ALA) during perinatal development (E0-P100), and a subset of rats fed the ALA- diet were switched to the ALA+ diet post-weaning (P21-P100, repletion). In adulthood (P100), plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) levels were measured. Additionally, indices of liver n-6 fatty acid biosynthesis, erythrocyte fatty acid composition, and regional brain monoamine turnover were determined. Indices of liver delta-6 desaturase activity were up-regulated in n-3-deficient rats, and were associated with greater erythrocyte membrane arachidonic acid (AA, 20:4 n-6) composition. Plasma IL-6 (p=0.001), TNFα (p=0.02), and CRP (p=0.001) concentrations were significantly greater in n-3-deficient rats relative to controls. The 5-HIAA/5-HT ratio was significantly greater in frontal cortex, hypothalamus, and ventral striatum of n-3-deficient rats relative to controls. Changes in membrane n-3 and n-6 fatty acid composition, elevations in plasma IL-6 and TNFα, and increased central 5-HT turnover were all prevented by normalization of n-3 fatty acid status. Erythrocyte docosahexaenoic acid (DHA, 22:6 n-3) was inversely correlated, and AA and the AA/DHA and AA/eicosapentaenoic acid ratios were positively correlated, with plasma IL-6, TNFα, and CRP levels. Plasma IL-6 levels were positively correlated with 5-HIAA/5-HT ratios in all brain regions. These preclinical data provide evidence for a functional link between n-3 fatty acid deficiency, elevated peripheral inflammatory signaling, and increased central 5-HT turnover.
Authors:
Robert K McNamara; Ronald Jandacek; Therese Rider; Patrick Tso; Allyson Cole-Strauss; Jack W Lipton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Prostaglandins, leukotrienes, and essential fatty acids     Volume:  83     ISSN:  1532-2823     ISO Abbreviation:  Prostaglandins Leukot. Essent. Fatty Acids     Publication Date:    2010 Oct-Dec
Date Detail:
Created Date:  2010-11-29     Completed Date:  2011-03-18     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  8802730     Medline TA:  Prostaglandins Leukot Essent Fatty Acids     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  185-91     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Psychiatry, University of Cincinnati College of Medicine, 260 Stetson Street, Suite 3306, Cincinnati, OH 45219-0516, USA. robert.mcnamara@uc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
C-Reactive Protein / metabolism
Cytokines / biosynthesis*
Fatty Acids, Omega-3 / metabolism*
Female
Inflammation Mediators / metabolism*
Interleukin-6 / metabolism
Lipids / deficiency
Male
Rats
Rats, Long-Evans
Serotonin / metabolism*
Tumor Necrosis Factor-alpha / metabolism
alpha-Linolenic Acid / metabolism
Grant Support
ID/Acronym/Agency:
DA017399/DA/NIDA NIH HHS; DK59630/DK/NIDDK NIH HHS; MH073704/MH/NIMH NIH HHS; MH074858/MH/NIMH NIH HHS; R21 MH073704-01A1/MH/NIMH NIH HHS; R21 MH074858-01A1/MH/NIMH NIH HHS; U24 DK059630-01/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Fatty Acids, Omega-3; 0/Inflammation Mediators; 0/Interleukin-6; 0/Lipids; 0/Tumor Necrosis Factor-alpha; 463-40-1/alpha-Linolenic Acid; 50-67-9/Serotonin; 9007-41-4/C-Reactive Protein
Comments/Corrections

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