Ileal sequencing of high fat diet fed Il22ra1fl/fl;Villin-cre mice

IL-22 is critical for ameliorating obesity-induced metabolic disorders. However, it is unknown where IL-22 acts to mediate these outcomes. Here we examine the importance of intestinal epithelium-specific IL-22RA1 signaling in mediating long-term high fat diet (HFD) driven metabolic disorders. We generated littermate control and knockout mice of the IL-22 receptor (IL-22RA1). Il22ra1fl/fl;Villin-cre- and cre+ mice were placed on long-term (16 weeks) of HFD. To assess how IL-22RA1 signaling mediates transcriptional programs post-HFD, we conducted RNA-sequencing on their ileal tissues at the end of this period. Overall, many key genes associated with lipid storage and metabolism were upregulated in the absence of IL-22RA1 signaling. These findings highlight the importance of tissue-specific IL-22RA1 signaling in mediating intestinal transcriptional metabolic programs post-HFD.