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肠道 IL-22RA1 信号转导调节内在和全身脂质和葡萄糖代谢，以减轻肥胖相关疾病。

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

机构信息

Department of Microbiology and Immunology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA.

College of Pharmacy, Oregon State University, Corvallis, OR, USA.

出版信息

Nat Commun. 2024 Feb 21;15(1):1597. doi: 10.1038/s41467-024-45568-6.

DOI:10.1038/s41467-024-45568-6
PMID:38383607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10881576/
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.

摘要

IL-22 对于改善肥胖引起的代谢紊乱至关重要。然而，尚不清楚 IL-22 在何处发挥作用来介导这些结果。在这里，我们研究了组织特异性 IL-22RA1 信号在介导长期高脂肪饮食 (HFD) 驱动的代谢紊乱中的重要性。为此，我们生成了肠道上皮细胞、肝脏和白色脂肪组织 (WAT) 特异性 Il22ra1 敲除和同窝对照小鼠。肠道上皮细胞和肝脏特异性 IL-22RA1 信号上调了全身葡萄糖代谢。肠道 IL-22RA1 信号还以依赖于微生物组的方式调节肝脏和 WAT 代谢。我们发现了一个与肠道 Oscillibacter 和升高的 WAT 炎症之间的关联，可能是由表达 Mmp12 的巨噬细胞引起的。从机制上讲，肠道脂质代谢基因的转录受 IL-22 调节，可能还受 IL-22 诱导的 IL-18 调节。最后，我们表明 Paneth 细胞特异性 IL-22RA1 信号在 HFD 后部分介导了全身葡萄糖代谢。总的来说，这些结果阐明了肠道上皮细胞特异性 IL-22RA1 信号在调节肠道代谢和缓解全身肥胖相关疾病方面的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/8628507e845d/41467_2024_45568_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/b26b8e1d283b/41467_2024_45568_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/b23e536dc0d2/41467_2024_45568_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/fe8fb1185fe2/41467_2024_45568_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/4dafa77ff7bd/41467_2024_45568_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/3e40cb58a0c4/41467_2024_45568_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/6c6e18807e0e/41467_2024_45568_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/8628507e845d/41467_2024_45568_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/b26b8e1d283b/41467_2024_45568_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/b23e536dc0d2/41467_2024_45568_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/fe8fb1185fe2/41467_2024_45568_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/4dafa77ff7bd/41467_2024_45568_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/3e40cb58a0c4/41467_2024_45568_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/6c6e18807e0e/41467_2024_45568_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f7/10881576/8628507e845d/41467_2024_45568_Fig7_HTML.jpg

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[3]
Murine gut microbial interactions exert antihyperglycemic effects.

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[4]
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J Inflamm Res. 2024-11-30

[5]
Association analysis of gut microbiota with LDL-C metabolism and microbial pathogenicity in colorectal cancer patients.

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[6]
Pain, obesity, adenosine salvage disruption, and smoking behavior mediate the effect of gut microbiota on sleep disorders: results from network Mendelian randomization and 16S rDNA sequencing.

Front Microbiol. 2024-7-31

[7]
Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver.

Hepatology. 2025-5-1

[8]
IL-22 promotes mucin-type O-glycosylation and MATH1 cell-mediated amelioration of intestinal inflammation.

Cell Rep. 2024-5-28

本文引用的文献

[1]
Peptide YY: A Paneth cell antimicrobial peptide that maintains gut commensalism.

Science. 2023-8-4

[2]
GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology.

Immunity. 2023-1-10

[3]
Interleukin-18 in metabolism: From mice physiology to human diseases.

Front Endocrinol (Lausanne). 2022

[4]
Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation.

Cell Stem Cell. 2022-9-1

[5]
Microbiota and adipocyte mitochondrial damage in type 2 diabetes are linked by Mmp12+ macrophages.

J Exp Med. 2022-7-4

[6]
IL-22 initiates an IL-18-dependent epithelial response circuit to enforce intestinal host defence.

Nat Commun. 2022-2-15

[7]
IL-17RA-signaling in Lgr5 intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment.

Immunity. 2022-2-8

[8]
Cutting Edge: Intestinal IL-17A Receptor Signaling Specifically Regulates High-Fat Diet-Mediated, Microbiota-Driven Metabolic Disorders.

J Immunol. 2021-10-15

[9]
High-fat diet-activated fatty acid oxidation mediates intestinal stemness and tumorigenicity.

Cell Rep. 2021-6-8

[10]
Western diet induces Paneth cell defects through microbiome alterations and farnesoid X receptor and type I interferon activation.

Cell Host Microbe. 2021-6-9

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