AGRP and overnutrition: Furthermore, Zhang et al. also demonstrated that IKKβ/NF-κB remains inactive in hypothalamic neurons; however, overnutrition atypically activates hypothalamic IKKβ/NF-κB through elevated endoplasmic reticulum stress in the hypothalamus and activates hypothalamic AGRP neurons, leading to increased production of orexigenic hormones [37].