TLR4 and obesity due to melanocortin 4 receptor deficiency: In obesity and insulin resistance, dysbiosis with increased intestinal permeability has been proposed to drive “metabolic endotoxemia”, whereby gut-derived lipopolysaccharides activate Toll-like receptor-4 and NF-κB, increase IL-6, TNF-α, IL-1β and hepatic C-reactive protein, disrupt tight junction proteins such as ZO-1 and promote low-grade inflammation and adipose-tissue insulin resistance; concomitantly, reduced short-chain fatty acid production and altered bile-acid and branched-chain amino-acid metabolism may reinforce adipocyte dysfunction and ectopic fat storage [52,53,59].