The gut microbiota reprograms intestinal lipid metabolism through long noncoding RNA Snhg9

• 成果类型: Article
• 署名作者: Wang, Yuhao; Wang, Meng; Chen, Jiaxin; Li, Yun; Kuang, Zheng; Dende, Chaitanya; Raj, Prithvi; Quinn, Gabriella; Hu, Zehan; Srinivasan, Tarun; Hassell, Brian; Ruhn, Kelly A.; Behrendt, Cassie L.; Liang, Tingbo; Dou, Xiaobing; Song, Zhangfa; Hooper, Lora V.
• 署名单位: Zhejiang University; Zhejiang Chinese Medical University; Zhejiang University; University of Texas System; University of Texas Southwestern Medical Center; Zhejiang University; Zhejiang University; Zhejiang University; Zhejiang University; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; Carnegie Mellon University; Shanghai Jiao Tong University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8419
• DOI: 10.1126/science.ade0522
• 发表日期: 2023-08-25
• 页码: 851-856
• 关键词: white adipose-tissue; host; sirt1; mice; expression; resistance; promotes; cells; differentiation; receptors

摘要

The intestinal microbiota regulates mammalian lipid absorption, metabolism, and storage. We report that the microbiota reprograms intestinal lipid metabolism in mice by repressing the expression of long noncoding RNA (lncRNA) Snhg9 (small nucleolar RNA host gene 9) in small intestinal epithelial cells. Snhg9 suppressed the activity of peroxisome proliferator-activated receptor ? (PPAR?)-a central regulator of lipid metabolism-by dissociating the PPAR? inhibitor sirtuin 1 from cell cycle and apoptosis protein 2 (CCAR2). Forced expression of Snhg9 in the intestinal epithelium of conventional mice impaired lipid absorption, reduced body fat, and protected against diet-induced obesity. The microbiota repressed Snhg9 expression through an immune relay encompassing myeloid cells and group 3 innate lymphoid cells. Our findings thus identify an unanticipated role for a lncRNA in microbial control of host metabolism.