Lipotoxicity- induced metabolic inflammation: potential role of ceramides in glial cells interaction and inflammatory-damage propagation

Abstract

Western diet is associated with the elevated rates of obesity and related metabolic disorders, also considered important risk factors for brain dysfunction. Chronic inflammation and insulin resistance comprise the most relevant shared pathways, promoting alterations in the plasticity of limbic structures such as the hippocampus. With the aim to study the impact of metabolic disturbances on the brain we focused on the role of glial cells in two different approaches: in vivo, in the hippocampus of C57BL/6 mice exposed to a high fat diet (HFD)and in vitro, emulating the lipotoxic context with the saturated fatty acid palmitate (PA) as an insult to microglia and astrocyte cell lines and the role of ceramide pathway. We have previously found that HFD mice exhibited decreased neurogenesis and structuralsynaptic alterations, together with spatial memory impairment and neuroinflammation, withincreased expression of hippocampal TNFα and IL1β cytokines and enlarged microglia.