Accordingly, tissue-specific loss of p85α in BAT is able to prevent HFD-induced obesity in mice by promoting the activation of BAT, the amelioration of the proinflammatory profile, and consequently leading to the improvement of systemic insulin sensitivity due in part to increased IRB/IRS-1 association and insulin signaling, as well as decreased JNK activation [142]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.