Intestinal IL-22RA1 signaling regulates intrinsic and systemic lipid and glucose metabolism to alleviate obesity-associated disorders

Stephen J. Gaudino, Ankita Singh, Huakang Huang, Jyothi Padiadpu, Makheni Jean-Pierre, Cody Kempen, Tej Bahadur, Kiyoshi Shiomitsu, Richard Blumberg, Kenneth R. Shroyer, Semir Beyaz, Natalia Shulzhenko, Andrey Morgun and Pawan Kumar ()
Additional contact information
Stephen J. Gaudino: Stony Brook University
Ankita Singh: Stony Brook University
Huakang Huang: Stony Brook University
Jyothi Padiadpu: Oregon State University
Makheni Jean-Pierre: Stony Brook University
Cody Kempen: Stony Brook University
Tej Bahadur: Stony Brook University
Kiyoshi Shiomitsu: Stony Brook University
Richard Blumberg: Harvard Medical School
Kenneth R. Shroyer: Stony Brook University
Semir Beyaz: Cold Spring Harbor Laboratory
Natalia Shulzhenko: Oregon State University
Andrey Morgun: Oregon State University
Pawan Kumar: Stony Brook University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45568-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45568-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45568-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().