The metabolic dysfunctions induced by high fat diet (HFD) consumption are not limited to organs involved in energy metabolism but cause also a chronic low-grade systemic
inflammation that affects the whole body including the central nervous system. The brain has been considered for a long time to be protected from systemic
inflammation by the blood-brain barrier, but more recent data indicated an association between
obesity and neurodegeneration. Moreover,
obesity-related consequences, such as
insulin and
leptin resistance,
mitochondrial dysfunction and
reactive oxygen species (ROS) production, may anticipate and accelerate the physiological aging processes characterized by systemic
inflammation and higher susceptibility to
neurological disorders. Here, we discussed the link between
obesity-related metabolic dysfunctions and
neuroinflammation, with particular attention to molecules regulating the interplay between energetic impairment and altered synaptic plasticity, for instance
AMP-activated protein kinase (AMPK) and
Brain-derived neurotrophic factor (
BDNF). The effects of HFD-induced
neuroinflammation on neuronal plasticity may be mediated by altered brain mitochondrial functions. Since mitochondria play a key role in synaptic areas, providing energy to support synaptic plasticity and controlling ROS production, the negative effects of HFD may be more pronounced in synapses. In conclusion, it will be emphasized how HFD-induced metabolic alterations, systemic
inflammation, oxidative stress,
neuroinflammation and impaired brain plasticity are tightly interconnected processes, implicated in the pathogenesis of neurological diseases.