Structural Brain Changes Associated with Overweight and Obesity

Figure 1

Pathogenesis of obesity-associated brain damage. Outside CNS: adipose tissue macrophages infiltrate the adipose tissue in obesity and contribute to insulin resistance. M1 or “classically activated” macrophages are induced by proinflammatory mediators, such as lipopolysaccharides and IFN-γ. M1 macrophages enhance proinflammatory cytokine production (TNF-α, IL-6, and IL-12), which can block the effects of insulin action on adipocytes (link between inflammation and insulin resistance) and generate reactive oxygen species (ROS), such as nitric oxide, via activation of iNOS (Nos2). Inside CNS: local and systemic inflammation induced by obesity can cause breakdown of the blood-brain barrier (BBB), a decrease in waste removal, and an increase in infiltration of immune cells. Microglia: activated microglia secrete proinflammatory cytokines (IL-1β, IL-6, TNF-α, and INF-γ), which stimulate inflammatory signaling in adjacent neurons, which in turn induces insulin and leptin resistance of neurons.