Foamy Monocytes Are Enriched in cis -7-Hexadecenoic Fatty Acid (16:1n-9), a Possible Biomarker for Early Detection of Cardiovascular Disease

Abstract

Human monocytes respond to arachidonic acid, a secretory product of endothelial cells, by activating the de novo pathway of fatty acid biosynthesis, resulting in the acquisition of a foamy phenotype due to accumulation of cytoplasmic lipid droplets. Recruitment of foamy monocytes to endothelium is a key step in the formation of atherosclerotic plaques. Here we describe that lipid droplets of foamy monocytes are enriched in a rather uncommon fatty acid, cis-7-hexadecenoic acid (16:1n-9), a positional isomer of palmitoleic acid. 16:1n-9 was found to possess an anti-inflammatory activity both in vitro and in vivo that is comparable with that of omega-3 fatty acids and clearly distinguishable from the effects of palmitoleic acid. Selective accumulation in neutral lipids of phagocytic cells of an uncommon fatty acid reveals an early phenotypic change that may provide a biomarker of proatherogenicity, and a potential target for intervention in the early stages of cardiovascular disease.

Fatty Acids in Membranes as Homeostatic, Metabolic and Nutritional Biomarkers: Recent Advancements in Analytics and Diagnostics

“…0.07%–0.1% [26,27]. Recently, a high level of this fatty acid was reported in human foamy monocytes, particularly in membrane phospholipids, suggesting its possible development as a biomarker for early detection of cardiovascular disease [28]. In this case, GC analysis was performed with dimethyloxazoline (DMOX) derivatives of cell membrane fatty acids, and in the GC run only one peak was detected for the delta-7 cis isomer superimposing with the delta-6 cis isomer (sapienic acid).…”

Small Drops Get Fat: Unexpected Fatty Acid in Cytoplasmic Lipid Droplets

“…Hence, Guijas et al (2016) have not only discovered an unexpected fatty acid in lipid droplets from human monocytes imprinted by extracellular arachidonic acid, but they also raised stimulating questions for biochemists, immunologists, and physicians to consider about the role of 16:1n9 in atherogenesis and its usefulness as a biomarker in early disease detection and possibly also as a therapeutic target.…”

“…In the present study, the Balsinde team therefore applied an improved chromatographic protocol and thus recognized that the 16:1 fatty acid accumulating in neutral lipids of activated monocytes is actually not 16:1n7 but an unidentified isomer (Guijas et al, 2016). A side-by-side comparison of the unidentified fatty acid with a number of known 16:1 isomers was first performed to strongly reduce the number of candidates and dimethyloxazoline (DMOX)-based fatty acid derivatization was subsequently used to demonstrate that the fatty acid accumulating in neutral lipids of arachidonic acid-pulsed monocytes is 16:1n9.…”

“…In a model of transcellular lipid biosynthesis, Guijas et al (2016), in this issue of Cell Chemical Biology, demonstrate that lipid droplet-containing ''foamy'' monocytes unexpectedly accumulate 16:1n9-palmitoleic acid, which has anti-inflammatory function in vitro and in vivo. This uncommon positional isomer of 16:1n7-palmitoleic acid represents a candidate biomarker for early cardiovascular disease detection.…”

“…Another intriguing aspect of the study by Guijas et al (2016) relates to the metabolic constellation where de novo fatty acid synthesis with concurrent fatty acid oxidation stimulates the generation of an unusual lipid with anti-inflammatory function. Such a metabolic scenario is reminiscent of the ''futile cycle'' recently described for T lymphocytes (O'Sullivan et al, 2014).…”