Dietary Fatty Acids in Postprandial Triglyceride-Rich Lipoproteins Modulate Human Monocyte-Derived Dendritic Cell Maturation and Activation

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.

An exploratory study on the role of serum fatty acids in the short-term dietary therapy of gingivitis

“…Besides omega-3 fatty acids, a large number of other serum fatty acids may influence inflammatory processes. Saturated fatty acids were shown to significantly increase post-prandial dendritic cell circulation (as a sign of innate immunity) in healthy volunteers in contrast to omega-3 poly-unsaturated fatty acids 25 . In a study published in 2010, by Ramirez-Tortosa et al, the levels of a broader spectrum of fatty acids were analyzed with regard to periodontitis 26 .…”

MUFAs in High‐Fat Diets Protect against Obesity‐Induced Bias of Hematopoietic Cell Lineages

“…[ 15 ] This mechanism would not be relevant, despite the role of macrophages and particularly dendritic cells as potent antigen presenting cells in adipose tissue, [ 51 ] as it has been demonstrated that HFDs enriched in MUFAs promote a surrounding lipid environment dominated by oleic acid and the prevalence of alternatively activated macrophages in eWAT [ 38 ] and that triglyceride‐rich lipoproteins isolated from volunteers after the ingestion of a high‐fat meal rich in olive oil impede maturation and pro‐inflammatory activation of monocyte‐derived dendritic cells. [ 52 ] In fact, the repression of the Elane gene in the visceral adipose depot may suggest that HFDs enriched in MUFAs did not induce the recruitment of neutrophils into eWAT. The lower cell death background in the spleen after HFDs enriched in MUFAs compared to HFD‐SFAs, which may be another proof of decreased inflammatory tone, [ 20 ] could have contributed to maintaining the survival of immune cells within this organ.…”

Mechanisms of Atherosclerosis Induced by Postprandial Lipemia

“…The endothelium plays a role in preventing the formation and development of AS through platelet aggregation, vascular tension, coagulation, and fibrinolysis ( 39 ). The activation of white blood cells and oxidative stress produced by monodietary fat meal may lead to endothelial dysfunction and form the early stages of AS ( 40 , 41 ).…”

“…The instability of lipid metabolism and chronic postprandial inflammation are the underlying pathogenesis of AS-induced CVD ( 41 ). ApoB100-containing lipoproteins enter the arterial subendothelium and are retained by interaction with membrane proteoglycans through charge-based interactions and sphingolipases.…”