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- Title
Glucocorticoid-induced Fingerprints on Visceral Adipose Tissue Transcriptome and Epigenome.
- Authors
García-Eguren, Guillermo; González-Ramírez, Mar; Vizán, Pedro; Giró, Oriol; Vega-Beyhart, Arturo; Boswell, Laura; Mora, Mireia; Halperin, Irene; Carmona, Francisco; Gracia, Meritxell; Casals, Gregori; Squarcia, Mattia; Enseñat, Joaquim; Vidal, Oscar; Di Croce, Luciano; Hanzu, Felicia A.
- Abstract
Context: Chronic glucocorticoid (GC) overexposure, resulting from endogenous Cushing's syndrome (CS) or exogenous GC therapy, causes several adverse outcomes, including persistent central fat accumulation associated with a low-grade inflammation. However, no previous multiomics studies in visceral adipose tissue (VAT) from patients exposed to high levels of unsuppressed GC during active CS or after remission are available yet. Objective: To determine the persistent VAT transcriptomic alterations and epigenetic fingerprints induced by chronic hypercortisolism. Methods: We employed a translational approach combining high-throughput data on endogenous CS patients and a reversible CS mouse model. We performed RNA sequencing and chromatin immunoprecipitation sequencing on histone modifications H3K4me3, H3K27ac, and H3K27me3) to identify persistent transcriptional and epigenetic signatures in VAT produced during active CS and maintained after remission. Results: VAT dysfunction was associated with low-grade proinflammatory status, macrophage infiltration, and extracellular matrix remodeling. Most notably, chronic hypercortisolism caused a persistent circadian rhythm disruption in VAT through core clock genes modulation. Importantly, changes in the levels of 2 histone modifications associated to gene transcriptional activation (H3K4me3 and H3K27ac) correlated with the observed differences in gene expression during active CS and after CS remission. Conclusion: We identified for the first time the persistent transcriptional and epigenetic signatures induced by hypercortisolism in VAT, providing a novel integrated view of molecular components driving the long-term VAT impairment associated with CS.
- Subjects
ADIPOSE tissues; CUSHING'S syndrome; CLOCK genes; GENE expression; EPIGENOMICS; HUMAN fingerprints; TRANSCRIPTOMES; GENETIC regulation; CIRCADIAN rhythms
- Publication
Journal of Clinical Endocrinology & Metabolism, 2022, Vol 107, Issue 1, p150
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/clinem/dgab662