linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability
Marcella E. O’Reilly,
Sebastian Ho,
Johana Coronel,
Lucie Zhu,
Wen Liu,
Chenyi Xue,
Eunyoung Kim,
Esther Cynn,
Caio V. Matias,
Rajesh Kumar Soni,
Chen Wang,
Iuliana Ionita-Laza,
Robert C. Bauer,
Leila Ross,
Yiying Zhang,
Silvia Corvera,
Susan K. Fried,
Muredach P. Reilly
Affiliations
Marcella E. O’Reilly
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Sebastian Ho
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Johana Coronel
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Lucie Zhu
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Wen Liu
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Chenyi Xue
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Eunyoung Kim
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Esther Cynn
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Caio V. Matias
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Rajesh Kumar Soni
Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA
Chen Wang
Department of Statistics, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA
Iuliana Ionita-Laza
Department of Statistics, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA
Robert C. Bauer
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Leila Ross
Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA
Yiying Zhang
Division of Molecular Genetics, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA
Silvia Corvera
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
Susan K. Fried
Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Muredach P. Reilly
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; Corresponding author
Summary: 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.
