linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability.

Autor:	O'Reilly ME; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Ho S; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Coronel J; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Zhu L; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Liu W; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Xue C; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Kim E; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Cynn E; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Matias CV; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Soni RK; Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA., Wang C; Department of Statistics, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA., Ionita-Laza I; Department of Statistics, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA., Bauer RC; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Ross L; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA., Zhang Y; Division of Molecular Genetics, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA., Corvera S; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA., Fried SK; Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Reilly MP; Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA; Irving Institute for Clinical and Translational Research, Columbia University, New York, NY 10032, USA. Electronic address: mpr2144@cumc.columbia.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 May 28; Vol. 43 (5), pp. 114240. Date of Electronic Publication: 2024 May 14.
DOI:	10.1016/j.celrep.2024.114240
Abstrakt:	Adipose tissue remodeling and dysfunction, characterized by elevated inflammation and insulin resistance, play a central role in obesity-related development of type 2 diabetes (T2D) and cardiovascular diseases. Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular functions. Here, we describe the functions of linc-ADAIN (adipose anti-inflammatory), an adipose lincRNA that is downregulated in white adipose tissue of obese humans. We demonstrate that linc-ADAIN knockdown (KD) increases KLF5 and interleukin-8 (IL-8) mRNA stability and translation by interacting with IGF2BP2. Upregulation of KLF5 and IL-8, via linc-ADAIN KD, leads to an enhanced adipogenic program and adipose tissue inflammation, mirroring the obese state, in vitro and in vivo. KD of linc-ADAIN in human adipose stromal cell (ASC) hTERT adipocytes implanted into mice increases adipocyte size and macrophage infiltration compared to implanted control adipocytes, mimicking hallmark features of obesity-induced adipose tissue remodeling. linc-ADAIN is an anti-inflammatory lincRNA that limits adipose tissue expansion and lipid storage. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu