Figure 3. Microglia in HFD-induced obesity and IL-1β/LPS-induced activation.

(a) In HFD-induced obesity, ARH microglia are activated, leading to hypothalamic inflammation with increased release of proinflammatory cytokines, increased expression of microglial UCP2, increased number of microglia and altered microglial morphology (microgliosis)^151,155,157. Of note, invalidating IKKB/ NF-_KB signalling selectively in AgRP neurons results in an anti-obesity and anti-diabetic phenotype in mice fed a HFD⁵⁸. (b) Anorexia induced by systemic administration of IL-1β prominently activates NF-_KB in tanycytes and microglia. This increases Cox2 expression and prostaglandin release mediating weight loss⁸⁵. NF-_KB activation also directly stimulates POMC transcription in LPS-induced illness¹⁴⁶. (c) Microglia of the ARH are sensitive to LPS (used to model sickness-induced anorexia) and saturated fatty acids (SFAs, which stimulate dietary inflammation), activating TLR4 to stimulate the release of proinflammatory cytokines and microglial activation¹⁴⁴. ARH, arcuate nucleus of hypothalamus; HFD, high fat diet; LPS, lipopolysaccharide; POMC, pro-opiomelanocortin; SFA, saturated fatty acids; TLR4, toll-like receptor; UCP2, uncoupled protein 2.