Outlining the human monocyte inflammatory cytokine response to dietary fat intake

Abstract

Whilst mounting evidence implicates innate immune cells such as monocytes and macrophages in the development of atherosclerotic cardiovascular disease, evidence supporting dietary saturated fat intake as an established risk factor has been a topic of recent controversy. Little however, is understood about the effects of acute dietary saturated fat intake on monocytes and their subsets. A dietary interventional study with a coconut oil meal, rich in lauric acid was utilised to investigate human monocyte subset responses to saturated fat intake, comparing fasting and postprandial monocytes in healthy human donors. Utilising ex vivo and in vitro experiments, monocyte subsets differed at baseline in terms of surface marker expression and that the CD16low subset accumulates cytoplasmic lipid droplets to a greater extent than their CD16high counterparts, but that neither subset mounts an inflammatory response to dietary saturated fat exposure at either surface protein or gene expression level. Somewhat unexpectedly however, both subsets of postprandial monocytes lost relative migratory ability towards a chemokine gradient following postprandial lipids exposure and downregulated their inflammatory responses when stimulated by bacterial or viral TLR cues. The effects were augmented further when utilising higher concentrations of postprandial triglycerides in the form of triglyceride-rich lipoproteins and replicated with other dietary lipid sources such as palm and olive oil. Utilising gas and liquid chromatography mass spectrometry, I demonstrated that this surprising immunoparetic phenotype may in part be due to intracellular changes in lipid metabolism and the accumulation of isomers of docosahexaenoic acid (DHA), a polyunsaturated fat with anti- inflammatory properties. Although a significant body of work suggests intake of dietary saturated fat may provoke an inflammatory response, ingestion of lauric and other fatty acids used in this study, in fact resulted in an immunoparetic response, which may be of importance in understanding atherogenesis and healthy eating in the context of immunity.