Acute in vivo elevation of intravascular triacylglycerol lipolysis impairs peripheral T cell activation in humans.
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.


METHODS
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.
Larbi
Anis
A
Division of Geriatrics, University of Sherbrooke, Sherbrooke, Québec, Canada.
Grenier
Amélie
A
Frisch
Frédérique
F
Douziech
Nadine
N
Fortin
Carl
C
Carpentier
André C
AC
Fülöp
Tamas
T
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015153:Blotting, Western; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D005217:Fat Emulsions, Intravenous; D005260:Female; D005434:Flow Cytometry; D015309:Glucose Clamp Technique; D006801:Humans; D019787:Linoleic Acid / Q000097:blood; D008066:Lipolysis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D018613:Microscopy, Confocal; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D014280:Triglycerides / Q000008:administration & dosage / Q000494:pharmacology*
D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D005217:Fat Emulsions, Intravenous; D008563:Membrane Lipids; D014280:Triglycerides; D002784:Cholesterol; D019787:Linoleic Acid