Acyl Chain Preference in Foam Cell Formation from Mouse Peritoneal Macrophages

Area of Science:

• Lipid Metabolism
• Atherosclerosis Research
• Cell Biology

Background:

• Macrophage foam cells are central to atherosclerosis development, primarily through cholesteryl ester accumulation.
• Previous research on foam cell lipid metabolism has largely overlooked the role of acyl chains, focusing instead on the sterol group.

Purpose of the Study:

• To investigate the impact of different acyl chain compositions in phosphatidylserine liposomes on macrophage foam cell formation.
• To elucidate the role of acyl chain characteristics in cholesterol metabolism and lipid droplet accumulation within macrophages.

Main Methods:

• Utilized a model system with liposomes containing specific acyl chains (unsaturated C18:1, saturated C16:0, C18:0) and phosphatidylserine.
• Employed [14C]cholesterol and [14C]fatty acyl chains to trace cholesterol uptake, esterification, and lipid synthesis.
• Conducted microscopic observations and metabolic analyses to assess lipid droplet formation and metabolic pathways.

Main Results:

• Unsaturated (C18:1) phosphatidylserine liposomes, but not saturated (C16:0, C18:0) ones, induced significant lipid droplet formation in macrophages.
• Cholesterol conversion to cholesteryl ester was essential for foam cell formation, occurring specifically with C18:1 phosphatidylserine liposomes.
• Cholesterol within C16:0 or C18:0 phosphatidylserine liposomes remained largely intact after endosomal uptake, while C18:1 liposomes facilitated cholesteryl ester and triacylglycerol synthesis.

Conclusions:

• The acyl chain composition of phosphatidylserine liposomes critically influences macrophage foam cell formation.
• Macrophage enzymatic machinery exhibits selectivity towards acyl chains, impacting cholesterol esterification and lipid droplet accumulation.
• These findings suggest that acyl chain preference plays a significant role in the progression of macrophages towards a foam cell phenotype.