We previously showed that gut microbial imbalance (i.e., dysbiosis) controls a state of metabolic endotoxemia during obesity and that bacterial factors from the gut, such as lipopolysaccharide (LPS), accumulated in the blood and contributed to inflammation and insulin intolerance through CD14/TLR4 pathogen-sensing systems (Cani et al, 2007, 2008; Poggi et al, 2007; Luche et al, 2013). Here, TLR4 is linked to obesity due to melanocortin 4 receptor deficiency.