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

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 γ (PPARγ)-a central regulator of lipid metabolism-by dissociating the PPARγ 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:381

Enthalten in:

Science (New York, N.Y.) - 381(2023), 6660 vom: 25. Aug., Seite 851-857

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Apoptosis Regulatory Proteins
CCAR1 protein, mouse
Cell Cycle Proteins
EC 3.5.1.-
Journal Article
PPAR gamma
RNA, Long Noncoding
Sirtuin 1

Anmerkungen:

Date Completed 28.08.2023

Date Revised 02.12.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1126/science.ade0522

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM361147333