Abstract
Dietary fatty acids have been demonstrated to modulate systemic inflammation and induce the postprandial inflammatory response of circulating immune cells. We hypothesized that postprandial triglyceride-rich lipoproteins (TRLs) may have acute effects on immunometabolic homeostasis by modulating dendritic cells (DCs), sentinels of the immunity that link innate and adaptive immune systems. In healthy volunteers, saturated fatty acid (SFA)-enriched meal raised serum levels of granulocyte/macrophage colony-stimulating factor GM-CSF (SFAs > monounsaturated fatty acids (MUFAs) = polyunsaturated fatty acids (PUFAs)) in the postprandial period. Autologous TRL-SFAs upregulated the gene expression of DC maturation (CD123 and CCR7) and DC pro-inflammatory activation (CD80 and CD86) genes while downregulating tolerogenic genes (PD-L1 and PD-L2) in human monocyte-derived DCs (moDCs). These effects were reversed with oleic acid-enriched TRLs. Moreover, postprandial SFAs raised IL-12p70 levels, while TRL-MUFAs and TRL-PUFAs increased IL-10 levels in serum of healthy volunteers and in the medium of TRL-treated moDCs. In conclusion, postprandial TRLs are metabolic entities with DC-related tolerogenic activity, and this function is linked to the type of dietary fat in the meal. This study shows that the intake of meals enriched in MUFAs from olive oil, when compared with meals enriched in SFAs, prevents the postprandial production and priming of circulating pro-inflammatory DCs, and promotes tolerogenic response in healthy subjects. However, functional assays with moDCs generated in the presence of different fatty acids and T cells could increase the knowledge of postprandial TRLs’ effects on DC differentiation and function.
Highlights
The emerging research topic called immunometabolism investigates mutual interactions between the immune system and the metabolism [1]
After an overnight fasting period of 12 h, all of them were given, over three different occasions, an oral fat emulsion containing cow’s milk cream, refined olive oil or refined olive oil plus a dose of omega-3 long-chain polyunsaturated fatty acids (PUFAs), which consisted of 920 mg of eicosapentaenoic acid (EPA) and 760 mg of docosahexaenoic acid (DHA)
The total area under the curve (AUCTOTAL ) values for serum granulocyte/macrophage colony-stimulating factor (GM-CSF) were significantly higher (p = 0.0170) only after the ingestion of the high-fat meal enriched in saturated fatty acid (SFA) in healthy volunteers (Figure 1b)
Summary
The emerging research topic called immunometabolism investigates mutual interactions between the immune system and the metabolism [1]. Contrariwise, the dysfunctional remodeling of intracellular metabolic pathways plays a critical role for the functions of immune cells [3]. The human-derived DC family are typically classified into two phenotypically and functionally subsets, plasmacytoid DCs (pDCs) and myeloid. In vitro homologous monocyte-derived DCs (moDCs), require the influence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for differentiation [5]. MoDCs undergo an activation process that, depending on their membrane receptors and secreted cytokines, means that moDCs may have either a pro-inflammatory or tolerogenic function. Pro-inflammatory activation is with CD80 and CD86 surface marker expression and IL-12p70 cytokine secretion, whereas PD-L1 and PD-L2 surface marker expression and IL-10 cytokine secretion are considered to prompt tolerogenic or anti-inflammatory activation of moDCs [6]
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