NFKB1 and obesity due to melanocortin 4 receptor deficiency: Considering that UPR may promote HIF through inositol-requiring enzyme 1α (IRE1α)-X box-binding protein 1 (XBP1) (69, 70), while IKK/NF-κB and ER stress promote each other and induce energy imbalance leading to obesity during HFD feeding (68), it can be inferred that HIF can act as downstream negative feedback to inhibit NF-κB in the process of ER stress, so as to reduce the adverse effects of this stress.