Indeed, previously, Schertzer showed that Nod1 ligands directly reduced insulin sensitivity in isolated primary hepatocytes at a concentration as low as 100 ng/mL of iE-DAP in a Nod1-dependent manner.7 We found that the level of Nod1 ligands in SPF mice was equivalent to approximately 1 μg/mL of iE-DAP, and thus in a similar range to a previous report.43 It is possible that Nod1 ligands circulating in blood in WT mice on normal chow was sufficient to produce relative insulin resistance. This evidence concerns the gene INS and Insulin resistance.