Figure 3.

Hypothetical model for the regulation of feeding, metabolic rate, and sickness behavior by hypothalamic cytokine signaling. In chronic disease elevated circulating cytokines stimulate the production of pro-inflammatory cytokines, including IL-1β and LIF, in the hypothalamus. These molecules then increase melanocortin signaling by directly activating POMC neurons and inhibiting AgRP neurons. This leads to decreased appetite and increased energy expenditure, primarily as basal metabolic rate, by increasing activation of MC4-R. Other elements of sickness behavior, including insulin resistance, lethargy, anhedonia, and reproductive axis failure may also result from inflammation-induced changes in melanocortin signaling