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

Autor: Gaudino SJ; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA., Singh A; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA., Huang H; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA., Padiadpu J; College of Pharmacy, Oregon State University, Corvallis, OR, USA., Jean-Pierre M; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA., Kempen C; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA., Bahadur T; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA., Shiomitsu K; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA., Blumberg R; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Shroyer KR; Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA., Beyaz S; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA., Shulzhenko N; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA., Morgun A; College of Pharmacy, Oregon State University, Corvallis, OR, USA., Kumar P; Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA. pawan.kumar@stonybrook.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 21; Vol. 15 (1), pp. 1597. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1038/s41467-024-45568-6
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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