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

Yuhao Wang, Meng Wang, Jiaxin Chen, Yun Li, Zheng Kuang, Chaitanya Dende, Prithvi Raj, Gabriella Quinn, Zehan Hu, Tarun Srinivasan, Brian Hassell, Kelly A. Ruhn, Cassie L. Behrendt, Tingbo Liang, Xiaobing Dou, Zhangfa Song, Lora V. Hooper

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

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 g (PPARg)—a central regulator of lipid metabolism—by dissociating the PPARg 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.

Original languageEnglish (US)
Pages (from-to)851-857
Number of pages7
JournalScience
Volume381
Issue number6660
DOIs
StatePublished - Aug 25 2023

ASJC Scopus subject areas

  • General

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