INS and obesity due to melanocortin 4 receptor deficiency: Another was that alteration of gut microbiota could damage the integrity of the intestinal epithelial barrier, change the intestinal permeability, and increase the lipopolysaccharide, a component of the cell wall of gram-negative bacteria in the intestinal tract, which entered circulation to cause an immune response, affected insulin signaling pathway, and thus promoted insulin resistance and obesity (Caricilli and Saad, 2014).