Differential effects of palmitoleic acid on human lymphocyte proliferation and function

Abstract

BackgroundPalmitoleic acid (PA) is a n-7 monounsaturated fatty acid (MUFA) secreted by adipose tissue and related to decreased insulin resistance in peripheral tissues. Evidences have been shown that PA also decreased proinflammatory cytokine expression in cultured macrophages. Although studies have shown that other fatty acids (FAs) modulate several lymphocyte functions, the specific effect of PA on these cells is unknown. The aim of the present study was to evaluate the possible influence of PA on activation and differentiation of human lymphocytes in comparison to oleic acid (OA).MethodsHuman lymphocytes were isolated from peripheral blood of health men and cultured in the presence of growing concentrations of PA or OA (5 to 200 μM), for 24 h. After that, cells were collected and cytotoxicity evaluated by flow cytometry. Then, we analyzed proliferative capacity in lymphocytes treated with non toxic concentrations of PA and OA (25 and 50 μM, respectively), in the presence or absence of concanavalin A (ConA). The Th1/Th2/Th17 cytokine production was determined by the Cytometric Bead Array. CD28 and CD95 surface expression and T regulatory cell percentage were determined by flow cytometry.ResultsWe observed that PA is toxic to lymphocytes above 50 μM. PA promoted a decrease of lymphocyte proliferation stimulated by ConA in both concentrations. PA also decreased CD28 externalization and increased CD95. On the other hand, OA did not alter these parameters. In the same way, PA reduced IL6, IFN-gamma, TNF-alpha and IL17A production in both concentration and IL2 only at 50 μM (in the presence of ConA). OA promoted IFN-gamma reduction in both concentrations and an increase of IL-2, IL4 and IL10 at 25 μM. Both fatty acids decreased the percentage of T regulatory cells.ConclusionIn conclusion, PA promoted a suppressive effect on lymphocyte proliferation characterized by a decrease of Th1 and Th17 response, and co-stimulatory molecule (CD28). However, OA increased lymphocyte proliferation through IL2 production and Th2 response. These results also show a more suppressive effect of PA on lymphocytes in comparison to OA.

Effect of Free Fatty Acids on Inflammatory Gene Expression and Hydrogen Peroxide Production by Ex Vivo Blood Mononuclear Cells

“…Dietary lipids modulate the innate and adaptive responses of immune system components [26][27][28][29]. In the present study, we showed that some FAs modulated proinflammatory gene expression in PBMCs and their ability to produce H 2 O 2 after 2 h stimulation with LPS.…”

“…In addition, omega-3 FAs can reverse low-grade inflammation in obesity by increasing the synthesis of pro-resolving mediators, such as resolvins, and decreasing proinflammatory mediators [33]. The mechanisms of FA effects on gene expression in PBMCs are not yet known, but it is probable that FAs can directly bind to membrane receptors or change intracellular protein activation [29], modulating TLRs [34] and NFκB [35] signaling pathways and, consequently, the inflammatory response.…”

Effects of high-oleic peanuts within a hypoenergetic diet on inflammatory and oxidative status of overweight men: a randomised controlled trial

“…Contrary to our results, Rocha et al demonstrate that MUFA high-fat meal consumption leads to a significant reduction in IL-17A postprandial response in healthy women with a high percentage of body fat (38) . Similarly, an in vitro study demonstrated an increase in IL-4 concentration after incubation with oleic acid, but not with palmitoleic acid (39) . Monocytes extracted from healthy men exhibit a higher concentration of IL-4 after acute consumption of a fat-enriched meal with MUFA and PUFA in comparison with the meal rich in SFA (40) .…”

Oleic acid Induces Tissue Resident FoxP3 Regulatory T cell Lineage Stability and Suppressive Functions

“…In animal tissues, oleic acid is one of the most abundant free fatty acids regardless of tissue or species ( 41–44 ), implying that tissue-resident T regs are sensing oleic acid, and that oleic acid may be an important signal for tissue-resident T regs . LCFAs can alter cellular proliferation and viability in a dose dependent manner ( 3, 45–51 ). However, at a concentration of 10μM of oleic acid, we observe increases in FOXP3 expression (Supplemental Figure 1A-B), but do not find any differences in T reg viability (Supplemental Figure 1C) or proliferation (Supplemental Figure 1D) in the presence of either oleic acid or arachidonic acid compared to vehicle.…”