Model depicting the hypothalamic response to an HFD in animals predisposed to DIO. A: AgRP and POMC neurons are integral components of energy balance neurocircuitry located in the ARC nucleus, situated adjacent
to the third cerebral ventricle (3V) along the floor of the hypothalamus. Activity of these neurons is sensitive to input
from circulating hormones (e.g., leptin and insulin) and nutrients, and it plays an important role to establish the defended
level of body weight. B: Recent evidence suggests that during HFD feeding, these neurons may be injured via unknown mechanisms, and that this injury
triggers activation of local glial cell populations (astrocytes and microglia). This neuron injury and reactive gliosis can
in turn impair homeostatic control of body fat stores, leading to increased body weight.