Fatty acids from very low-density lipoprotein lipolysis products induce lipid droplet accumulation in human monocytes.
One mechanism by which monocytes become activated postprandially is by exposure to triglyceride-rich lipoproteins such as very low-density lipoproteins (VLDL). VLDL are hydrolyzed by lipoprotein lipase at the blood-endothelial cell interface, releasing free fatty acids. In this study, we examined postprandial monocyte activation in more detail, and found that lipolysis products generated from postprandial VLDL induce the formation of lipid-filled droplets within cultured THP-1 monocytes, characterized by coherent antistokes Raman spectroscopy. Organelle-specific stains revealed an association of lipid droplets with the endoplasmic reticulum, confirmed by electron microscopy. Lipid droplet formation was reduced when lipoprotein lipase-released fatty acids were bound by BSA, which also reduced cellular inflammation. Furthermore, saturated fatty acids induced more lipid droplet formation in monocytes compared with mono- and polyunsaturated fatty acids. Monocytes treated with postprandial VLDL lipolysis products contained lipid droplets with more intense saturated Raman spectroscopic signals than monocytes treated with fasting VLDL lipolysis products. In addition, we found that human monocytes isolated during the peak postprandial period contain more lipid droplets compared with those from the fasting state, signifying that their development is not limited to cultured cells but also occurs in vivo. In summary, circulating free fatty acids can mediate lipid droplet formation in monocytes and potentially be used as a biomarker to assess an individual's risk of developing atherosclerotic cardiovascular disease.
den Hartigh
Laura J
LJ
Division of Endocrinology, Department of Internal Medicine, University of California, Davis, Davis, CA 95616, USA.
Connolly-Rohrbach
Jaime E
JE
Fore
Samantha
S
Huser
Thomas R
TR
Rutledge
John C
JC
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D004797:Enzyme-Linked Immunosorbent Assay; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008066:Lipolysis / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000648:ultrastructure; D019518:Postprandial Period / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D055815:Young Adult
D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D014409:Tumor Necrosis Factor-alpha