Acute effects of dietary fatty acids on osteclastogenesis via RANKL/RANK/OPG system

3 Figuras.-- 2 TablasScope: Postprandial state is directly linked with chronic diseases. We hypothesized that dietary fats may have acute effects on health status by modulating osteoclast differentiation and activation in a fatty acid-dependent manner. Methods and results: In healthy subjects, a fat-enriched meal increased plasma levels of the RANKL (receptor activator of nuclear factor κB ligand)/OPG (osteoprotegerin) ratio (SFAs > MUFAs = PUFAs) in the postprandial state. Postprandial TRL-SFAs enhanced tartrate-resistant acid phosphatase (TRAP) activity and the expression of osteoclast marker genes (TRAP, OSCAR, RANK, and CATHK) while downregulated the expression of OPG gene in human monocyte-derived osteoclasts. These effects were not observed with monounsaturated fatty acid (MUFA)-enriched postprandial triglyceride-rich lipoproteins (TRLs). Moreover, postprandial TRL-SFAs increased the release of osteoclastogenic cytokines (TNF-α, IL-1β, and IL-6) meanwhile TRL-MUFAs and TRL-PUFAs increased the release of anti-osteoclastogenic cytokines (IL-4 and IL-10) in the medium of human monocyte-derived osteoclasts. Conclusion: For the first time, we show that postprandial TRLs are metabolic entities with osteoclastogenic activity and that this property is related to the type of dietary fatty acid in the meal. The osteoclastogenic potency was as follows: SFAs >>> MUFAs = PUFAs. These exciting findings open opportunities for developing nutritional strategies with olive oil as the principal dietary source of MUFAs, notably oleic acid, to prevent development and progression of osteoclast-related diseases.This study was supported by the research Grant AGL2011‐29008 (Spanish Ministry of Science and Innovation, MICINN). S.M. has the benefit of a FPI fellowship (BES‐2012‐056104) of MICINN. B.B. and S.L. acknowledges financial support from “V Own Research Plan” (University of Seville) and the Spanish Research Council (CSIC)/Juan de la Cierva, respectively. We thank the students (Pablo de Olavide University) who participated in this study. We are also grateful to Arturo Navarro for his technical expertise