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Adipocyte Glucocorticoid Receptor Inhibits Immune Regulatory Genes to Maintain Immune Cell Homeostasis in Adipose Tissue

TitleAdipocyte Glucocorticoid Receptor Inhibits Immune Regulatory Genes to Maintain Immune Cell Homeostasis in Adipose Tissue
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2023
AuthorsAmatya, Shripa, Tietje-Mckinney Dylan, Mueller Schaefer, Petrillo Maria Grazia, Woolard Matthew D., Bharrhan Sushma, Orr Anthony Wayne, Kevil Christopher G., Cidlowski John A., and Cruz-Topete Diana
JournalEndocrinology (United States)
Type of ArticleArticle
Keywords3T3-L1 cell line, adipocyte, Adipocytes, adipocytokine, adiponectin, adipose tissue, adipose tissue inflammation, albumin, animal, animal cell, animal experiment, animal tissue, Animals, article, body weight, brown adipose tissue, chemokine receptor CXCR2, cholinergic receptor, cholinergic receptor nicotinic alpha 9, cochlin, controlled study, cre recombinase, Deoxyribonuclease I, epididymis fat, Female, Flow cytometry, gene expression level, Genes, genetics, glucocorticoid, glucocorticoid receptor, haptoglobin, homeostasis, immobilization stress, immune-related gene, immunocompetent cell, Immunofluorescence, Immunoglobulin, immunoglobulin heavy constant mu, immunoregulation, in vivo study, inflammation, insulin sensitivity, isoflurane, Knockout, knockout mouse, Leptin, limit of detection, macrophage migration, male, mesenteric fat, Messenger, messenger RNA, metabolism, Mice, microarray analysis, mouse, nonhuman, programmed death 1 ligand 1, promoter region, prophylaxis, protein blood level, protein cemip, protein cleavage, protein expression, real time polymerase chain reaction, Receptors, Regulator, regulator gene, resistin, retroperitoneal fat, RNA, serine proteinase inhibitor, serpin family a member 3, sex difference, signal transduction, stromal vascular fraction, subcutaneous tissue, transcription factor Ets, unclassified drug, white adipose tissue

Glucocorticoids acting via the glucocorticoid receptors (GR) are key regulators of metabolism and the stress response. However, uncontrolled or excessive GR signaling adversely affects adipose tissue, including endocrine, immune, and metabolic functions. Inflammation of the adipose tissue promotes systemic metabolic dysfunction; however, the molecular mechanisms underlying the role of adipocyte GR in regulating genes associated with adipose tissue inflammation are poorly understood. We performed in vivo studies using adipocyte-specific GR knockout mice in conjunction with in vitro studies to understand the contribution of adipocyte GR in regulating adipose tissue immune homeostasis. Our findings show that adipocyte-specific GR signaling regulates adipokines at both mRNA and plasma levels and immune regulatory (Coch, Pdcd1, Cemip, and Cxcr2) mRNA gene expression, which affects myeloid immune cell presence in white adipose tissue. We found that, in adipocytes, GR directly influences Cxcr2. This chemokine receptor promotes immune cell migration, indirectly affecting Pdcd1 and Cemip gene expression in nonadipocyte or stromal cells. Our findings suggest that GR adipocyte signaling suppresses inflammatory signals, maintaining immune homeostasis. We also found that GR signaling in adipose tissue in response to stress is sexually dimorphic. Understanding the molecular relationship between GR signaling and adipose tissue inflammation could help develop potential targets to improve local and systemic inflammation, insulin sensitivity, and metabolic health. © 2023 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.


Cited by: 1

Citation KeyAmatya2023
PubMed ID37738419