奥地利因斯布鲁克医科大学Timon E. Adolph团队宣布他们的研究开发出了上皮细胞RXRα代谢应激感应将饮食西化与克罗恩病联系起来。2025年12月8日出版的《细胞—代谢》杂志发表了这项成果。

通过CD的小肠转录谱分析，该研究组发现维甲酸X受体α (RXRα)的转录活性增加，特别是在肠上皮细胞（IECs）中。西方饮食中过量的ω-3和ω-6多不饱和脂肪酸（PUFA）可诱导小鼠IECs的RXRα转录活性。PUFA诱导的Paneth细胞中的RXRα活性通过激活CXCL1的表达来控制慢性跨壁肠炎。在两种小鼠模型中，口服异维甲酸可改善PUFA诱导的代谢性肠炎，在对170597名患者的电子医疗记录的分析中，异维甲酸治疗可降低发生CD的几率。总的来说，课题组人员发现Paneth细胞中的RXRα是一种代谢应激传感器，可引起肠炎，为预防和治疗CD提供了新的视角。

据悉，饮食西化，部分以长链脂肪酸过量为特征，扰乱了克罗恩病（CD）的肠道免疫反应。肠道炎症中脂质感知的细胞和分子框架仍然是谜。

附：英文原文

Title: Metabolic stress sensing by epithelial RXRα links westernization of diet with Crohn’s disease

Author: Moritz Meyer, Felix Grabherr, Christina Plattner, Michel V. Hadjihannas, Zhigang Rao, Valentin Marteau, Víctor Alonso López-Agudelo, Julian Schwrzler, Lisa Mayr, Almina Jukic, Laura Scheffauer, Luis Zundel, Barbara Enrich, Alexandra Pfister, Anna Simonini, Christoph Grander, Richard Hilbe, David Haschka, Andreas Zollner, Kathrin Vouk, Patrizia Moser, Michael W. Hess, Niloofar Nemati, Dietmar Rieder, Felix Sommer, Philip Rosenstiel, Qitao Ran, Richard S. Blumberg, Arthur Kaser, Florian Rieder, Andreas Koeberle, Christoph Becker, Raja Atreya, Anja A. Kühl, Britta Siegmund, Andre Franke, Herbert Tilg, Zlatko Trajanoski, Timon E. Adolph

Issue&Volume: 2025-12-08

Abstract: Westernization of diet, partly characterized by long-chain fatty acid excess, perturbs intestinal immune responses in Crohn’s disease (CD). The cellular and molecular framework of lipid sensing in intestinal inflammation remains enigmatic. By small intestinal transcriptional profiling of CD, we identified increased transcriptional activity of retinoid X receptor alpha (RXRα) specifically in intestinal epithelial cells (IECs). Transcriptional RXRα activity was induced in IECs of mice by ω-3 and ω-6 polyunsaturated fatty acid (PUFA) excess in a Western diet. PUFA-induced RXRα activity in Paneth cells governed chronic transmural enteritis by enabling the expression of CXCL1. Oral exposure to isotretinoin ameliorated PUFA-induced metabolic enteritis in two mouse models, and isotretinoin therapy reduced the odds of developing CD in an analysis of electronic health care records from 170,597 patients. Collectively, we identify RXRα in Paneth cells as a metabolic stress sensor that enables enteritis, providing novel perspectives for the prevention and treatment of CD.

DOI: 10.1016/j.cmet.2025.11.008

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00492-9