Metabolic lipotoxicity-induced neuroinflammation: potential role of glial cells interaction via extracellular vesicles.

ANGELES VINUESA; MELINA BELLOTTO; MELISA BENTIVEGNA; AMAL GREGOSA; CARLOS POMILIO; JESSICA PRESA; JUAN BEAUQUIS; FLAVIA SARAVIA

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2020

Obesity and related metabolic disorders are important risk factors for brain aging, promotingalterations in the plasticity of limbic structures such as the hippocampus. Among the underlyingmechanisms, chronic inflammation and insulin resistance are crucial factors, also associated withalterations of sphingolipid metabolism. Taking this into account, we intend to study mechanismsassociated with the impact of metabolic disturbances on the brain. We aim to assessthe inflammatoryresponse induced by a lipotoxic context and the communication between glial cells mediated by therelease of extracellular vesicles (EVs) as vehicles of damage propagation.We previously found that C57BL/6 mice exposed to a high fat diet (HFD) presentedneuroinflammation, decreased neurogenesis and structural synaptic alterations, together with spatialmemory impairment. To assess potential mechanisms involved, we used an in vitro approachemulating the lipotoxic context with the saturated fatty acid palmitate (PA). Microglial culturesexposed to PA showed a pro-inflammatory profile and, after purification of EVs from the conditionedmedia (CM), we found that exosomes altered dendritic spine morphology of hippocampal neurons.Here, we show that in the presence of ceramide synthesis inhibitor Cambinol, the induced expressionof IL1β in PA-exposed BV2 microglial cells was diminished (p