To achieve this, we used the previously reported WT and mutants of Jak3 [29] to characterize the role of global Jak3 in the gut–brain communication and used a novel tissue-specific Jak3-KO mouse model to confirm the IEC-specific role of Jak3 in gut–brain communication and obesity/diabetes-associated cognitive impairment characteristic. This evidence concerns the gene JAK3 and obesity due to melanocortin 4 receptor deficiency.