Gaudino, Stephen J, Singh, Ankita, Huang, Huakang, Padiadpu, Jyothi, Jean-Pierre, Makheni, Kempen, Cody, Bahadur, Tej, Shiomitsu, Kiyoshi, Blumberg, Richard, Shroyer, Kenneth R, Beyaz, Semir, Shulzhenko, Natalia, Morgun, Andrey, Kumar, Pawan (February 2024) Intestinal IL-22RA1 signaling regulates intrinsic and systemic lipid and glucose metabolism to alleviate obesity-associated disorders. Nature Communications, 15 (1). p. 1597. ISSN 2041-1723 (Public Dataset)
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Abstract
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 tissue-specific IL-22RA1 signaling in mediating long-term high fat diet (HFD) driven metabolic disorders. To do so, we generated intestinal epithelium-, liver-, and white adipose tissue (WAT)-specific Il22ra1 knockout and littermate control mice. Intestinal epithelium- and liver-specific IL-22RA1 signaling upregulated systemic glucose metabolism. Intestinal IL-22RA1 signaling also mediated liver and WAT metabolism in a microbiota-dependent manner. We identified an association between Oscillibacter and elevated WAT inflammation, likely induced by Mmp12 expressing macrophages. Mechanistically, transcription of intestinal lipid metabolism genes is regulated by IL-22 and potentially IL-22-induced IL-18. Lastly, we show that Paneth cell-specific IL-22RA1 signaling, in part, mediates systemic glucose metabolism after HFD. Overall, these results elucidate a key role of intestinal epithelium-specific IL-22RA1 signaling in regulating intestinal metabolism and alleviating systemic obesity-associated disorders.
| Item Type: | Paper |
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| Subjects: | diseases & disorders organism description > animal diseases & disorders > inflammation organs, tissues, organelles, cell types and functions > organs types and functions > liver organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions > organs types and functions organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Shared Resources > Sequencing Technology & Analysis Service CSHL labs > Beyaz lab CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 21 February 2024 |
| Date Deposited: | 01 Mar 2024 13:33 |
| Last Modified: | 29 Apr 2024 17:44 |
| PMCID: | PMC10881576 |
| Related URLs: | |
| Dataset ID: |
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| URI: | https://repository.cshl.edu/id/eprint/41449 |
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