Unsaponifiable and phenolic fractions from virgin olive oil prevent neuroinflammation skewing microglia polarization toward M2 phenotype

[Display omitted] •The minor compounds from virgin olive oil prevent microglia activation toward M1 phenotype.•The minor compounds from virgin olive oil prevent neuroinflammation in obese mice.•Dietary virgin olive oil could prevent development and progression of neuroinflammation-related diseases. Inhibiting M1 microglia phenotype while stimulating M2 microglia phenotype has been suggested as potential therapeutic approach for the treatment of neuroinflammation-related diseases. Our aim was to evaluate the anti-neuroinflammatory effects of minor compounds found in unsaponifiable fraction (UF) and in phenolic fraction (PF) of virgin olive oil (VOO) in BV-2 microglial cells and in brain of mice with high-fat diet (HFD)-induced obesity by RT-qPCR, ELISA and flow cytometry techniques. We observed that UF and PF enhance M2 microglia polarization, whereas LPS polarized microglia prone to M1 phenotype. In addition, in contrast to dietary SFAs, dietary VOO primed for a reduced pro-inflammatory profile in the brain of mice. These findings unveil a potential beneficial role for minor compounds of VOO in regulating the plasticity of microglia. These exciting findings open opportunities for developing nutraceutical strategies with olive oil as principal source of fat to prevent development and progression of neuroinflammation-related diseases.