The role of the intestinal microbiota in the latter pathway has not been proved directly; however, evidence shows that altered intestinal microbiota and consequently altered metabolites, including short-chain fatty acids (SCFAs) and amino acid, are associated with peripheral insulin sensitivity and circulating insulin levels in patients with obesity or T2DM 69, which emphasizes the potential of the intestinal microbiota to induce central insulin resistance. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.