In our current study (Fig. 7g), we utilized novel IEC monolayers and organoid ex vivo models derived from mice, including Nts- and Ntsr1-deficient mice, as well as human tissue to demonstrate that NTS contributes to impaired AMPK signaling in IECs associated with HFD-induced obesity. Here, PRKAA2 is linked to obesity due to melanocortin 4 receptor deficiency.