INS and obesity due to melanocortin 4 receptor deficiency: For example, genetic or pharmacological inhibition of IκB kinase β (IKKβ), a primary and canonical upstream mediator of the NF-κB pathway in innate immunity, can restore weight gain and insulin sensitivity in mice with high-fat diet (HFD)-induced obesity8–11, suggesting that NF-κB activation is essential for obesity-induced inflammation and insulin resistance.