title: Role of macrophage activation in the lipid metabolism of postprandial triacylglycerol-rich lipoproteins.
abstract: The potential link between the inflammatory effects of postprandial lipemia and the induction of macrophage foam cell formation by triacylglycerol-rich lipoproteins (TGRL) was studied using postprandial triacylglycerol-rich lipoproteins (ppTGRL) derived from human volunteers and primary human monocyte-derived macrophages (HMDM). Subjects were fed a test meal high in dairy fat, followed three hours later by isolation of serum ppTGRL. Pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes were induced in HMDM by treatment with lipopolysaccharide (LPS) or dexamethasone (DEX), respectively. ppTGRL caused a dose-dependent increase in both triacylglycerol (TG) and cholesterol (CH) accumulation in the cells. TG accumulation was unaffected by LPS or DEX treatment, but LPS as compared with DEX-treated HMDM were found to accumulate more CH, and this effect was greater than that induced by ppTGRL in untreated cells. LPS-treatment had no effect on lipid uptake from ppTGRL (via the LDLr, scavenger receptors or SR-B1) or on CH efflux, but the CH synthesis inhibitor mevinolin abolished the difference between CH accumulation in LPS-and DEX-treated cells, suggesting that CH synthesis is enhanced in the inflammatory state. Phospholipid (PL) synthesis was increased in inflammatory M1 as compared with anti-inflammatory M2 HMDM. Moreover, TG synthesis was decreased by ppTGRL in DEX-treated as compared with untreated cells. We conclude, therefore, inflammation causes a greater increase in the accumulation of neutral lipids than ppTGRL in macrophages, and that this effect is related to modulation of PL metabolism and possibly also CH synthesis. Thus, the inflammatory phenotype of macrophages influences their lipid metabolism, and is, therefore, likely to modulate the induction of macrophage lipid accumulation by lipoproteins associated with foam cell formation.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Napolitano
authors.forename: Simona
authors.initials: S
authors.lastname: Sennato
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Botham
authors.forename: Federico
authors.initials: F
authors.lastname: Bordi
authors.forename: Elena
authors.initials: E
authors.lastname: Bravo
mesh_terms: D000328:Adult; D001782:Blood Donors; D002478:Cells, Cultured; D004032:Diet / Q000379:methods; D005260:Female; D006805:Human Experimentation; D006801:Humans; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D008297:Male; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D008074:Lipoproteins; D014280:Triglycerides