Our findings demonstrate that IKKβ deficiency in VTA DNs (i) suppresses binge eating of HFD in female mice; (ii) suppresses HFD-induced inflammation accompanied by suppression of glial cell activation in the VTA of female mice; (iii) improves insulin resistance induced by HFD in the VTA of female mice; (iv) alters the dopamine-related gene expressions in female mice; and (v) does not affect energy balance. Here, IKBKB is linked to Insulin resistance.