Figure 3.

Proposed role of neuroinflammation in obesity-associated cognitive and emotional alterations. Obesity is characterized by metabolic alterations (hyperinsulinemia, hyperleptinemia, increased activation of the hypothalamo-pituitary-adrenal (HPA) axis…) and peripheral low-grade inflammation, which originates from alterations in adipose tissue and gut functions. These obesity-associated alterations are well-known to promote brain inflammatory processes that represent key players in the development of behavioral alterations associated with obesity. By sustaining neuroinflammation, as manifested by chronic activation of microglia, brain production of inflammatory cytokines, and local activation of indoleamine 2,3-dioxygenase (IDO) and guanosine-triphosphate-cyclohydrolase-1 (GTP-CH1), obesity may impair monoaminergic neurotransmission, neurogenesis, and synaptic plasticity, and concomitantly promote neurotoxicity. Such alterations of brain function induced by neuroinflammation likely represent major pathophysiological pathways to cognitive and emotional alterations in obesity.