دورية أكاديمية
P029 Loss of adipose tissue protects mice from intestinal inflammation
| العنوان: | P029 Loss of adipose tissue protects mice from intestinal inflammation |
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| المؤلفون: | Omar, T, Letizia, M, Siegmund, B, Weidinger, C |
| المصدر: | Journal of Crohn's and Colitis ; volume 18, issue Supplement_1, page i285-i285 ; ISSN 1873-9946 1876-4479 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Gastroenterology, General Medicine |
| الوصف: | Background Crohn’s disease (CD) is associated with creeping fat, characterized by hyperplasia of mesenteric adipocytes and increased secretion of various adipokines, including leptin. Leptin can promote intestinal inflammation by inducing pro-inflammatory cytokines such as TNFα in murine and human lymphocytes. Recent meta-analyses have shown that increased body mass index (BMI) increases the risk of developing CD. However, whether the surgical removal of mesenteric fat could improve the outcome of CD patients and the impact of fat-derived signals on intestinal autoimmunity remain elusive. Methods To decipher the role of adipose tissue in the regulation of intestinal autoimmunity, we investigated here how the absence of adipose tissue affects epithelial barrier functions and immune cell homeostasis. Therefore, we studied lipoatrophic Ppargfl/fl-Adipoq-Cre mice, that completely lack adipose tissue, under steady-state conditions and after induction of chronic dextran sodium sulfate (DSS)-mediated inflammation, as well as in allogeneic fat transplantation models. We characterized our models using flow cytometry, RNA sequencing, immunohistochemistry, western blot analyses, ELISA and calcium measurements. Results At steady state, lipoatrophic mice showed a decrease in CD4 IL-17+ T cells in the ileum, and lower frequencies of CD8 T cells and CD4 FoxP3+ cells in the colon, suggesting that fat-derived signals are required for proper T cell homeostasis in mice. To understand how the absence of adipose tissue affects the severity of intestinal inflammation, we challenged lipoatrophic or WT littermates with 3 cycles of 1.5% DSS, which induced weight loss in both WT and lipoatrophic mice. However, only fat-proficient WT mice developed severe colitis, whereas lipoatrophic animals had significantly reduced intestinal inflammation and displayed disturbances in the differentiation and function of pro-inflammatory T cells including Th1 and Th17 cells. Importantly, these defects in T cell function could be rescued by ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/ecco-jcc/jjad212.0159 |
| الإتاحة: | https://doi.org/10.1093/ecco-jcc/jjad212.0159Test https://academic.oup.com/ecco-jcc/article-pdf/18/Supplement_1/i285/56347547/jjad212.0159.pdfTest |
| حقوق: | https://academic.oup.com/pages/standard-publication-reuse-rightsTest |
| رقم الانضمام: | edsbas.C55B6A74 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/ecco-jcc/jjad212.0159 |
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