Phenol-Enriched Virgin Olive Oil Promotes Macrophage-Specific Reverse Cholesterol Transport In Vivo

Abstract

The intake of olive oil (OO) enriched with phenolic compounds (PCs) promotes ex vivo HDL-mediated macrophage cholesterol efflux in humans. We aimed to determine the effects of PC-enriched virgin OO on reverse cholesterol transport (RevCT) from macrophages to feces in vivo. Female C57BL/6 mice were given intragastric doses of refined OO (ROO) and a functional unrefined virgin OO enriched with its own PC (FVOO) for 14 days. Our experiments included two independent groups of mice that received intragastric doses of the phenolic extract (PE) used to prepare the FVOO and the vehicle solution (saline), as control, for 14 days. FVOO intake led to a significant increase in serum HDL cholesterol and its ability to induce macrophage cholesterol efflux in vitro when compared with ROO group. This was concomitant with the enhanced macrophage-derived [3H]cholesterol transport to feces in vivo. PE intake per se also increased HDL cholesterol levels and significantly promoted in vivo macrophage-to-feces RevCT rate when compared with saline group. PE upregulated the expression of the main macrophage transporter involved in macrophage cholesterol efflux, the ATP binding cassettea1. Our data provide direct evidence of the crucial role of OO PCs in the induction of macrophage-specific RevCT in vivo.

This work was partly funded by the Instituto de Salud Carlos III and FEDER “Una manera de hacer Europa” grants PI14-01648 and PI18-00164 (to F.B.-V.), PI16-00139 and PI19-00136 (to J.C.E-G), and CB06/03/0028 (to M.F. (Montserrat Fitó)); by the Ministerio de Economía, Indústria y Competitividad and FEDER AppleCOR Project (subproject AGL2016-76943-C2-2-R and subproject AGL2016- 76943-C2-1-R) (to R.S.), AGL2009-13517-C03-01 and AGL2012-40144-C03-01 (to M.F. (Montserrat Fitó)); by the Agència de Gestió d’Ajuts Universitaris i de Recerca 2014-SGR-240, 2017-SGR-522, 2017-SGR-222, and 2017-BP-00021; by the Jane and Aatos Erkko Foundation (to M.J. and J.M.); and the Finnish Foundation for Cardiovascular Research (to M.J.). M.F. (Marta Farràs) has a Sara Borrell contract (CD17/00233). CIBERDEM and CIBEROBN are initiatives of the Instituto de Salud Carlos III.