IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45568-6.html
   My bibliography  Save this article

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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Natali, 2024. "Intestinal IL-22RA1 signaling regulates intrinsic and systemic lipid and glucose metabolism to alleviate obesity-associated disorders," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45568-6
    DOI: 10.1038/s41467-024-45568-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45568-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-45568-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Toshiro Sato & Johan H. van Es & Hugo J. Snippert & Daniel E. Stange & Robert G. Vries & Maaike van den Born & Nick Barker & Noah F. Shroyer & Marc van de Wetering & Hans Clevers, 2011. "Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts," Nature, Nature, vol. 469(7330), pages 415-418, January.
    2. Evan D. Rosen & Bruce M. Spiegelman, 2006. "Adipocytes as regulators of energy balance and glucose homeostasis," Nature, Nature, vol. 444(7121), pages 847-853, December.
    3. Xiaoting Wang & Naruhisa Ota & Paolo Manzanillo & Lance Kates & Jose Zavala-Solorio & Celine Eidenschenk & Juan Zhang & Justin Lesch & Wyne P. Lee & Jed Ross & Lauri Diehl & Nicholas van Bruggen & Gan, 2014. "Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes," Nature, Nature, vol. 514(7521), pages 237-241, October.
    4. Wenjing Yang & Tianming Yu & Xiangsheng Huang & Anthony J. Bilotta & Leiqi Xu & Yao Lu & Jiaren Sun & Fan Pan & Jia Zhou & Wenbo Zhang & Suxia Yao & Craig L. Maynard & Nagendra Singh & Sara M. Dann & , 2020. "Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    5. Hung-Yu Chiang & Hsueh-Han Lu & Janaki N. Sudhakar & Yu-Wen Chen & Nien-Shin Shih & Yi-Ting Weng & Jr-Wen Shui, 2022. "IL-22 initiates an IL-18-dependent epithelial response circuit to enforce intestinal host defence," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    6. Caroline A. Lindemans & Marco Calafiore & Anna M. Mertelsmann & Margaret H. O’Connor & Jarrod A. Dudakov & Robert R. Jenq & Enrico Velardi & Lauren F. Young & Odette M. Smith & Gillian Lawrence & Juli, 2015. "Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration," Nature, Nature, vol. 528(7583), pages 560-564, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Marco Calafiore & Ya-Yuan Fu & Paola Vinci & Viktor Arnhold & Winston Y. Chang & Suze A. Jansen & Anastasiya Egorova & Shuichiro Takashima & Jason Kuttiyara & Takahiro Ito & Jonathan Serody & Susumu N, 2023. "A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Tianqun Lang & Runqi Zhu & Xiao Zhu & Wenlu Yan & Yu Li & Yihui Zhai & Ting Wu & Xin Huang & Qi Yin & Yaping Li, 2023. "Combining gut microbiota modulation and chemotherapy by capecitabine-loaded prebiotic nanoparticle improves colorectal cancer therapy," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Natalia Di Tommaso & Antonio Gasbarrini & Francesca Romana Ponziani, 2021. "Intestinal Barrier in Human Health and Disease," IJERPH, MDPI, vol. 18(23), pages 1-23, December.
    4. Melkaye G Melka & Michal Abrahamowicz & Gabriel T Leonard & Michel Perron & Louis Richer & Suzanne Veillette & Daniel Gaudet & Tomáš Paus & Zdenka Pausova, 2013. "Clustering of the Metabolic Syndrome Components in Adolescence: Role of Visceral Fat," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-7, December.
    5. Ravikanth Nanduri & Takashi Furusawa & Alexei Lobanov & Bing He & Carol Xie & Kimia Dadkhah & Michael C. Kelly & Oksana Gavrilova & Frank J. Gonzalez & Michael Bustin, 2022. "Epigenetic regulation of white adipose tissue plasticity and energy metabolism by nucleosome binding HMGN proteins," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Shuting Li & Chia-Wen Lu & Elia C. Diem & Wang Li & Melanie Guderian & Marc Lindenberg & Friederike Kruse & Manuela Buettner & Stefan Floess & Markus R. Winny & Robert Geffers & Hans-Hermann Richnow &, 2022. "Acetyl-CoA-Carboxylase 1-mediated de novo fatty acid synthesis sustains Lgr5+ intestinal stem cell function," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Meiqi Fan & Eun-Kyung Kim & Young-Jin Choi & Yujiao Tang & Sang-Ho Moon, 2019. "The Role of Momordica charantia in Resisting Obesity," IJERPH, MDPI, vol. 16(18), pages 1-17, September.
    8. Ihab Ansari & Llorenç Solé-Boldo & Meshi Ridnik & Julian Gutekunst & Oliver Gilliam & Maria Korshko & Timur Liwinski & Birgit Jickeli & Noa Weinberg-Corem & Michal Shoshkes-Carmel & Eli Pikarsky & Era, 2023. "TET2 and TET3 loss disrupts small intestine differentiation and homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Qi Liu & Charles A Herring & Quanhu Sheng & Jie Ping & Alan J Simmons & Bob Chen & Amrita Banerjee & Wei Li & Guoqiang Gu & Robert J Coffey & Yu Shyr & Ken S Lau, 2018. "Quantitative assessment of cell population diversity in single-cell landscapes," PLOS Biology, Public Library of Science, vol. 16(10), pages 1-29, October.
    10. Jina Yun & Simon Hansen & Otto Morris & David T. Madden & Clare Peters Libeu & Arjun J. Kumar & Cameron Wehrfritz & Aaron H. Nile & Yingnan Zhang & Lijuan Zhou & Yuxin Liang & Zora Modrusan & Michelle, 2023. "Senescent cells perturb intestinal stem cell differentiation through Ptk7 induced noncanonical Wnt and YAP signaling," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    11. Andrew K. Beppu & Juanjuan Zhao & Changfu Yao & Gianni Carraro & Edo Israely & Anna Lucia Coelho & Katherine Drake & Cory M. Hogaboam & William C. Parks & Jay K. Kolls & Barry R. Stripp, 2023. "Epithelial plasticity and innate immune activation promote lung tissue remodeling following respiratory viral infection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    12. Zahraa Al Bander & Marloes Dekker Nitert & Aya Mousa & Negar Naderpoor, 2020. "The Gut Microbiota and Inflammation: An Overview," IJERPH, MDPI, vol. 17(20), pages 1-21, October.
    13. Polychronis Pavlidis & Anastasia Tsakmaki & Eirini Pantazi & Katherine Li & Domenico Cozzetto & Jonathan Digby- Bell & Feifei Yang & Jonathan W. Lo & Elena Alberts & Ana Caroline Costa Sa & Umar Niazi, 2022. "Interleukin-22 regulates neutrophil recruitment in ulcerative colitis and is associated with resistance to ustekinumab therapy," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    14. Xingxing Ren & Qiuyuan Liu & Peirong Zhou & Tingyue Zhou & Decai Wang & Qiao Mei & Richard A. Flavell & Zhanju Liu & Mingsong Li & Wen Pan & Shu Zhu, 2024. "DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    15. Gregory Alexander Raciti & Francesca Fiory & Michele Campitelli & Antonella Desiderio & Rosa Spinelli & Michele Longo & Cecilia Nigro & Giacomo Pepe & Eduardo Sommella & Pietro Campiglia & Pietro Form, 2018. "Citrus aurantium L. dry extracts promote C/ebpβ expression and improve adipocyte differentiation in 3T3-L1 cells," PLOS ONE, Public Library of Science, vol. 13(3), pages 1-20, March.
    16. Yadong Qi & Jiamin He & Yawen Zhang & Qiwei Ge & Qiwen Wang & Luyi Chen & Jilei Xu & Lan Wang & Xueqin Chen & Dingjiacheng Jia & Yifeng Lin & Chaochao Xu & Ying Zhang & Tongyao Hou & Jianmin Si & Shuj, 2023. "Heat-inactivated Bifidobacterium adolescentis ameliorates colon senescence through Paneth-like-cell-mediated stem cell activation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    17. Liang Yang & Zifeng Ruan & Xiaobing Lin & Hao Wang & Yanmin Xin & Haite Tang & Zhijuan Hu & Yunhao Zhou & Yi Wu & Junwei Wang & Dajiang Qin & Gang Lu & Kerry M. Loomes & Wai-Yee Chan & Xingguo Liu, 2024. "NAD+ dependent UPRmt activation underlies intestinal aging caused by mitochondrial DNA mutations," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    18. Lu Jia & Yiyang Jiang & Lili Wu & Jingfei Fu & Juan Du & Zhenhua Luo & Lijia Guo & Junji Xu & Yi Liu, 2024. "Porphyromonas gingivalis aggravates colitis via a gut microbiota-linoleic acid metabolism-Th17/Treg cell balance axis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    19. Jong Hoon Won & Jacob S. Choi & Joon-Il Jun, 2022. "CCN1 interacts with integrins to regulate intestinal stem cell proliferation and differentiation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Simone Isling Pærregaard & Line Wulff & Sophie Schussek & Kristoffer Niss & Urs Mörbe & Johan Jendholm & Kerstin Wendland & Anna T. Andrusaite & Kevin F. Brulois & Robert J. B. Nibbs & Katarzyna Sitni, 2023. "The small and large intestine contain related mesenchymal subsets that derive from embryonic Gli1+ precursors," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45568-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.