Postprandial triglyceride-rich lipoproteins promote M1/M2 microglia polarization in a fatty-acid-dependent manner

Inhibiting M1 microglia phenotype while stimulating the M2 microglia has been suggested as a potential therapeutic approach for the treatment of neuroinflammatory diseases. Our hypothesis is that the type of dietary fatty acids (FAs) into human postprandial triglyceride-rich lipoproteins (TRLs) could modulate the plasticity of microglia. We isolated TRLs at the postprandial hypertriglyceridemic peak from blood samples of healthy volunteers after the ingestion of a meal rich in saturated FAs (SFAs), monounsaturated FAs (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated FAs. We observed that postprandial TRL-MUFAs enhance M2 microglia polarization, whereas postprandial TRL-SFAs made polarized microglia prone to an M1 phenotype. In addition, in contrast to dietary SFAs, dietary MUFAs primed for a reduced proinflammatory profile in the brain of mice fed with the different FA-enriched diets. Our study underlines a role of postprandial TRLs as a metabolic entity in regulating the plasticity of microglia and brings an understanding of the mechanisms by which dietary FAs are environmental factors fostering the innate immune responsiveness. These exciting findings open opportunities for developing nutraceutical strategies with olive oil as the principal source of MUFAs, notably oleic acid, to prevent development and progression of neuroinflammation-related diseases.