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

Autor: Wang Y; Zhejiang Provincial Key Laboratory of Pancreatic Disease of The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.; School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China.; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310029, China.; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Wang M; Zhejiang Provincial Key Laboratory of Pancreatic Disease of The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China., Chen J; Department of Breast Surgery and Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China., Li Y; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Kuang Z; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Dende C; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Raj P; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Quinn G; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Hu Z; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Srinivasan T; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Hassell B; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Ruhn KA; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Behrendt CL; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Liang T; Zhejiang Provincial Key Laboratory of Pancreatic Disease of The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, China.; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310029, China., Dou X; School of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China., Song Z; Department of Colorectal Surgery and Key Laboratory of Biotherapy of Zhejiang Province, Sir Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, China., Hooper LV; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.; The Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2023 Aug 25; Vol. 381 (6660), pp. 851-857. Date of Electronic Publication: 2023 Aug 24.
DOI: 10.1126/science.ade0522
Abstrakt: 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.
Databáze: MEDLINE
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