Postprandial triglyceride-rich lipoproteins regulate perilipin-2 and perilipin-3 lipid-droplet-associated proteins in macrophages

J Nutr Biochem. 2015 Apr;26(4):327-36. doi: 10.1016/j.jnutbio.2014.11.007. Epub 2014 Dec 15.


Lipid accumulation in macrophages contributes to atherosclerosis. Within macrophages, lipids are stored in lipid droplets (LDs); perilipin-2 and perilipin-3 are the main LD-associated proteins. Postprandial triglyceride (TG)-rich lipoproteins induce LD accumulation in macrophages. The role of postprandial lipoproteins in perilipin-2 and perilipin-3 regulation was studied. TG-rich lipoproteins (TRLs) induced the levels of intracellular TGs, LDs and perilipin-2 protein expression in THP-1 macrophages and in Apoe(-/-) mice bone-marrow-derived macrophages with low and high basal levels of TGs. Perilipin-3 was only synthesized in mice macrophages with low basal levels of TGs. The regulation was dependent on the fatty acid composition of the lipoproteins; monounsaturated and polyunsaturated fatty acids (PUFAs) more strongly attenuated these effects compared with saturated fatty acids. In THP-1 macrophages, immunofluorescence microscopy and freeze-fracture immunogold labeling indicated that the lipoproteins translocated perilipin-3 from the cytoplasm to the LD surface; only the lipoproteins that were rich in PUFAs suppressed this effect. Chemical inhibition showed that lipoproteins induced perilipin-2 protein expression through the peroxisome proliferator-activated nuclear receptor (PPAR) PPARα and PPARγ pathways. Overall, our data indicate that postprandial TRLs may be involved in atherosclerotic plaque formation through the regulation of perilipin-2 and perilipin-3 proteins in macrophages. Because the fatty acid composition of the lipoproteins is dependent on the type of fat consumed, the ingestion of olive oil, which is rich in monounsaturated fatty acids, and fish oil, which is rich in omega-3 fatty acids, can be considered a good nutritional strategy to reduce the risk of atherosclerosis by LD-associated proteins decrease.

Keywords: Fatty acids; Lipid droplets; Macrophages; Perilipin-2; Perilipin-3; Triglyceride-rich lipoproteins.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Butter
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cross-Over Studies
  • Fatty Acids / administration & dosage
  • Fatty Acids / blood
  • Fatty Acids, Monounsaturated / administration & dosage
  • Fatty Acids, Monounsaturated / blood
  • Fatty Acids, Unsaturated / administration & dosage
  • Fatty Acids, Unsaturated / blood
  • Fish Oils / administration & dosage
  • Gene Expression Regulation
  • Humans
  • Lipoproteins / blood*
  • Macrophages / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Olive Oil / administration & dosage
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Perilipin-2
  • Perilipin-3
  • Postprandial Period*
  • Triglycerides / blood*
  • Young Adult


  • Carrier Proteins
  • Fatty Acids
  • Fatty Acids, Monounsaturated
  • Fatty Acids, Unsaturated
  • Fish Oils
  • Lipoproteins
  • Membrane Proteins
  • Olive Oil
  • PPAR alpha
  • PPAR gamma
  • Perilipin-2
  • Perilipin-3
  • Plin3 protein, mouse
  • Triglycerides
  • lipoprotein triglyceride
  • Butter