FIGURE 2.

Schematic representation of interglial crosstalk via chemokines and costimulatory molecules in hypothalamic inflammation under obese conditions. In the hypothalamus, glial cells such as astrocytes and microglia can directly respond to peripheral excess nutrient signals, such as FAs, through a unique vascular system (fenestrated capillaries) and damaged BBB and these glial cells become reactive to release inflammatory mediators. In obese environments rich in FAs, astrocytes accumulate lipid droplets, and they release the proinflammatory chemokine MCP-1, which promotes microglia migration, proliferation, and activation. The lipid-laden astrocytes can also directly interact with the migrated microglia through membrane-bound costimulatory receptors/ligands such as 4-1BB/4-1BBL, thus reinforcing the inflammation. This glial cell-mediated inflammatory crosstalk may be crucial for obesity-induced hypothalamic inflammation. BBB, blood–brain barrier; FFA, free fatty acid; MCP-1, monocyte chemoattractant protein-1; CCR2, C–C chemokine receptor type 2.