For example, HFD feeding-induced activation of IKKβ/NF-κB proinflammatory pathway in the hypothalamus [34-37;40], whether its upstream signaling event being ER stress [34;36], autophagy defect [40], or TLR activation [36;37], ultimately leads to increased energy intake, decreased energy expenditure, and the development of obesity. The gene discussed is IKBKB; the disease is obesity due to melanocortin 4 receptor deficiency.