Oleanolic Acid-Enriched Olive Oil Alleviates the Interleukin-6 Overproduction Induced by Postprandial Triglyceride-Rich Lipoproteins in THP-1 Macrophages

Abstract

Oleanolic acid (OA), a triterpene that is highly present in olive leaves, has been proposed as a component of functional foods for the prevention of metabolic syndrome, due to its anti-inflammatory activity. We analyzed the effects of OA on inflammatory parameters and signaling proteins in LPS-stimulated THP-1 macrophages. Thus, THP-1 macrophages were incubated with LPS for 48 h after pretreatment with OA at different concentrations. Pretreatment with OA was significantly effective in attenuating IL-6 and TNF-α overproduction induced by LPS in macrophages, and also improved the levels of AMPK-α. We also evaluated the effects of human triglyceride-rich lipoproteins (TRLs) derived from individuals consuming an OA-enriched functional olive oil. For this purpose, TRLs were isolated from healthy adolescents before, 2 and 5 h postprandially after the intake of a meal containing the functional olive oil or common olive oil, and were incubated with THP-1 macrophages. THP-1 macrophages incubated with TRLs isolated at 2 h after the consumption of the OA-enriched olive oil showed significant lower levels of IL-6 compared to the TRLs derived from olive oil. Our results suggest that OA might have potential to be used as a lipid-based formulation in functional olive oils to prevent inflammatory processes underlying metabolic syndrome in adolescents.

Keywords: THP-1 macrophages; adolescents; functional foods; human triglyceride-rich lipoproteins; insulin resistance; metabolic syndrome; obesity; oleanolic acid; olive oil; postprandial trial.

Figure 1

Effects of OA on proinflammatory cytokines production by THP-1 macrophages induced by LPS. Control cells were incubated with DMSO. Experiments performed in triplicate. (a) IL-1β; (b) IL-6; (c) TNF-α. Different letters indicate significant difference (p < 0.05) by one-way ANOVA analysis and Tukey’s post hoc test.

Figure 2

Effects of OA on AMPK-α (a) and Akt (b) in THP-1 macrophages induced by LPS. Control cells were incubated with DMSO. Experiments performed in triplicate. Different letters indicate significant difference (p < 0.05) by one-way ANOVA analysis and Tukey’s post hoc test.

Figure 3

TRL production of proinflammatory cytokines by THP-1 macrophages incubated with TRLs obtained from healthy adolescents before, and at 2 and 5 h after the intake an OA-enriched olive oil or non-functional olive oil. Control cells incubated with PBS. (a) IL-1β; (b) IL-6; (c) TNF-α. * p < 0.05.

Figure 4

Levels of AMPK-α (a), Akt (b) and NF-κB (c) in THP-1 macrophages incubated with TRL obtained from healthy adolescents before, and at 2 and 5 h after the intake an OA-enriched olive oil or non-functional olive oil. Control cells incubated with PBS. * p < 0.05.

Figure 5

Oil red O microphotographs of THP-1 macrophages incubated for 48 h in the presence or absence (control) of TRLs obtained before, and at 2 and 5 h after the consumption of the olive oils. (a) Control; (b) 0 h TRL; (c) 2 h TRL; (d) 5 h TRL.