Document Detail


Acute in vivo elevation of intravascular triacylglycerol lipolysis impairs peripheral T cell activation in humans.
MedLine Citation:
PMID:  16280424     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Previous studies have shown suppressive effects of polyunsaturated fatty acids (PUFAs) on T cell proliferation, but the precise mechanism for this effect has not been fully investigated in vivo in humans. OBJECTIVE: The objective was to determine whether this effect is the result of altered T cell membrane properties and impaired CD3- and CD28-mediated signaling in vivo in humans. DESIGN: Peripheral T cells were isolated from healthy subjects before and 2 h after an intravenous infusion of heparin plus a PUFA-rich lipid emulsion during a euglycemic hyperinsulinemic clamp to induce a 2.5-fold elevation in plasma linoleic acid concentration without significant change in plasma total free fatty acid concentrations. RESULTS: Intravenous infusion of heparin plus the lipid emulsion reduced peripheral T cell membrane fluidity and altered lipid raft organization, both of which were associated with reduced T cell proliferation after stimulation with CD3 plus CD28. Tyrosine phosphorylation of linker of activated T cells and activation of protein kinase B in T cells were also impaired without a reduction in T cell receptor expression. In addition, acute PUFA elevation was associated with a reduction in T cell membrane cholesterol exchange with the cellular milieu ex vivo. CONCLUSIONS: A selective increase in plasma linoleic acid concentration and in intravascular lipolysis has a suppressive effect on peripheral T cell CD28-dependent activation, and this effect is associated with changes in plasma membrane properties. Our results have important implications for nutritional therapy in patients at high risk of septic complications and may also be of relevance to postprandial lipid metabolism disorders such as insulin resistance and type 2 diabetes.
Authors:
Anis Larbi; Amélie Grenier; Frédérique Frisch; Nadine Douziech; Carl Fortin; André C Carpentier; Tamas Fülöp
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of clinical nutrition     Volume:  82     ISSN:  0002-9165     ISO Abbreviation:  Am. J. Clin. Nutr.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-11-10     Completed Date:  2005-12-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376027     Medline TA:  Am J Clin Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  949-56     Citation Subset:  AIM; IM    
Affiliation:
Division of Geriatrics, University of Sherbrooke, Sherbrooke, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antigens, CD28 / immunology
Antigens, CD3 / immunology
Antigens, Differentiation, T-Lymphocyte / immunology*
Blotting, Western
Cell Division / drug effects
Cholesterol / metabolism
Fat Emulsions, Intravenous
Female
Flow Cytometry
Glucose Clamp Technique
Humans
Linoleic Acid / blood
Lipolysis / immunology
Lymphocyte Activation / drug effects*,  physiology
Male
Membrane Fluidity / drug effects
Membrane Lipids / chemistry,  metabolism*
Microscopy, Confocal
Middle Aged
T-Lymphocytes / immunology*,  ultrastructure
Triglycerides / administration & dosage,  pharmacology*
Chemical
Reg. No./Substance:
0/Antigens, CD28; 0/Antigens, CD3; 0/Antigens, Differentiation, T-Lymphocyte; 0/Fat Emulsions, Intravenous; 0/Membrane Lipids; 0/Triglycerides; 2197-37-7/Linoleic Acid; 57-88-5/Cholesterol
Comments/Corrections
Comment In:
Am J Clin Nutr. 2006 Apr;83(4):918; author reply 918-9   [PMID:  16600947 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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