Acute dietary saturated fat intake suppresses human monocyte subset inflammatory and chemokine responses

Abstract

Abstract Background Dietary saturated fat (SF) intake is implicated in increasing cardiovascular risk. Studies suggest SF may incite an inflammatory immune response yet the mechanisms for this remain unclear. Circulating blood monocyte subsets (classical “CD16low” and non-classical/intermediate “CD16high”) are thought to differentially contribute to the macrophage foam cell burden in atherosclerotic plaque, yet they are heterogenous and much is still unknown about their response to dietary lipid. Purpose This dietary intervention study hypothesised that a subset-specific monocyte response occurs following acute SF intake in healthy individuals.Top of Form Methods 10 healthy participants were fed a coconut oil, lauric acid-rich meal. Monocyte subsets were purified from fasting and 4h postprandial blood by fluorescence activated cytometry (FACS) into CD16low and CD16high subsets. Surface marker expression was recorded by FACS, gene expression by qPCR, lipid loading by fluorescence microscopy, cytokine responses by ELISA and mass spectrometry was utilised to trace dietary fat into circulating monocytes. Triglyceride rich lipoprotein (TGRL) was obtained through ultracentrifugation of postprandial blood. TLR agonists LPS (TLR4) and R848 (TLR7/8) were used to replicate infectious stimuli to provoke a cytokine response. Results SF meal intake resulted in a 4h postprandial rise in serum triglycerides (TG). Other than a small rise in HLA-DR in postprandial CD16low monocytes, no changes in CD14, CD16 or CD11c levels were noted. Inflammatory gene expression was downregulated although a rise in lipid handling gene ABCA1 was noted in both subsets. Postprandial monocytes accumulated cytoplasmic neutral lipid droplets (larger and more numerate droplets in CD16low). Mass-spectrometry confirmed entry of dietary lipid into circulating monocytes. Postprandial monocyte functional responses were impaired; lipid-loaded postprandial monocytes were less able to migrate towards a chemokine gradient. Following TLR challenge, the inflammatory response was abrogated in postprandial monocytes, further suppressed by in vitro postprandial TGRL addition. Lipidomic analyses confirmed postprandial monocyte lauric acid accumulation in the form of free fatty acid and TG trilaurin, and 9(S)-, 13(S)-HODE and 17(S)-HDoHE, that are metabolites of docosahexanoic acid (DHA) and possess anti-inflammatory properties. The attached graphical abstract summarises the pertinent findings. Conclusions Acute dietary SF intake of a lauric acid-rich meal results in postprandial monocyte suppression of inflammatory TLR responses, a reduction in the ability to migrate towards a chemokine gradient whilst accumulating cytoplasmic neutral lipid droplets. The immunosuppression may be caused by accumulation of anti-inflammatory metabolites of DHA. Graphical Abstract Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation, UK