scholarly journals MiR-122-5p: A Novel Biomarker of Glucocorticoid Action

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A89-A89
Author(s):  
Dimitrios Chantzichristos ◽  
Per-Arne Svensson ◽  
Terence Garner ◽  
Camilla A M Glad ◽  
Brian Robert Walker ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Network Analysis ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Isotonic Saline ◽  
Learning Approaches ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Glucocorticoid Action

Abstract Background: Glucocorticoids are among the most prescribed medications for various indications, and treatment with glucocorticoids is associated with increased morbidity and mortality. A biomarker allowing quantification of glucocorticoid action could improve treatment safety and efficacy. Objective: To identify and validate circulating biomarkers of glucocorticoid action using a clinical experimental study and multi-omic network analysis. Methods: In a randomized, controlled, crossover, single-blind trial, 10 subjects without endogenous glucocorticoid production (Addison’s disease) received intravenous hydrocortisone infusion in a circadian pattern (physiological glucocorticoid exposure) or isotonic saline (glucocorticoid withdrawal) over 22 hours. Food intake and sample collections were standardized during both treatment periods. The transcriptomes of peripheral blood mononuclear cells and adipose tissue, plasma miRNAome and serum metabolome were collected at 7 AM (end of infusion). These multi-omic data were compared between the two interventions, within and between subjects, using network analysis of higher order interactions along with statistical and machine learning approaches. Samples from 120 subjects with varying glucocorticoid exposure from independent studies were used for the replication of the miRNA findings. The study was pre-registered at ClinicalTrials.gov with identifier NCT02152553. Results: We identified a transcriptomic profile derived from both peripheral blood mononuclear cells and adipose tissue, and a multi-omic signature including genes, miRNAs and metabolites that were associated with glucocorticoid exposure. Within the multi-omic signature we identified a single microRNA (miR-122-5p, p=0.009) regulated by glucocorticoid exposure, which we then replicated as a novel biomarker of glucocorticoid action in 120 subjects from independent studies (0.01 ≤ p ≤ 0.05). Conclusions: The discovery of miR-122-5p as a novel circulating biomarker of glucocorticoid action may have a significant impact on clinical practice. Our data also improves the understanding of glucocorticoid action and may have impact on future studies on the mechanistic understanding for the role of glucocorticoids in the etiology of common diseases, such as cardiovascular disease and obesity.

scholarly journals Effects of cold exposure revealed by global transcriptomic analysis in ferret peripheral blood mononuclear cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bàrbara Reynés ◽  
Evert M. van Schothorst ◽  
Jaap Keijer ◽  
Andreu Palou ◽  
Paula Oliver
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Peripheral Blood Mononuclear Cells ◽  
Cold Exposure ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Cycle Gene ◽  
Peripheral Blood Mononuclear ◽  
Brown Adipose ◽  
Blood Mononuclear Cells

AbstractAnimal studies, mostly performed in rodents, show the beneficial anti-obesity effects of cold studies. This is due to thermogenic activation of brown adipose tissue (BAT), a tissue also recently discovered in adult humans. Studies in humans, however, are hampered by the accessibility of most tissues. In contrast, peripheral blood mononuclear cells (PBMC) are accessible and share the expression profile of different sets of genes with other tissues, including those that reflect metabolic responses. Ferrets are an animal model physiologically closer to humans than rodents. Here, we investigated the effects on ferrets of one-week acclimation to 4 °C by analysing the PBMC transcriptome. Cold exposure deeply affected PBMC gene expression, producing a widespread down-regulation of genes involved in different biological pathways (cell cycle, gene expression regulation/protein synthesis, immune response, signal transduction, and genes related to extracellular matrix/cytoskeleton), while thermogenic and glycogenolysis-related processes were increased. Results obtained in PBMC reflected those of adipose tissue, but hardly those of the liver. Our study, using ferret as a model, reinforce PBMC usefulness as sentinel biological material for cold-exposure studies in order to deepen our understanding of the general and specific pathways affected by cold acclimation. This is relevant for future development of therapies to be used clinically.

scholarly journals Effect of high-fat diet on peripheral blood mononuclear cells and adipose tissue in early stages of diet-induced weight gain

2019 ◽  
Vol 122 (12) ◽  
pp. 1359-1367 ◽  
Author(s):  
Jake E. Lowry ◽  
Batbayar Tumurbaatar ◽  
Claudia D’Agostino ◽  
Erika Main ◽  
Traver J. Wright ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
High Fat Diet ◽  
Time Course ◽  
Mononuclear Cells ◽  
High Fat ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Inflammatory Changes

AbstractSubcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.

scholarly journals Impaired alternative macrophage differentiation of peripheral blood mononuclear cells from obese subjects

2011 ◽  
Vol 9 (3) ◽  
pp. 189-195 ◽  
Author(s):  
Gael Bories ◽  
Robert Caiazzo ◽  
Bruno Derudas ◽  
Corinne Copin ◽  
Violeta Raverdy ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
The Metabolic Syndrome ◽  
Blood Mononuclear Cells ◽  
Obese Subjects ◽  
Anti Inflammatory

Visceral obesity is a chronic, low-grade inflammatory disease that predisposes people to the metabolic syndrome, type 2 diabetes and its cardiovascular complications. Adipose tissue is not a passive storehouse for fat, but an endocrine organ synthesizing and releasing a variety of bioactive molecules, some of which are produced by infiltrated immune-inflammatory cells including macrophages. Two different subpopulations of macrophages have been identified in adipose tissue: pro-inflammatory ‘classical’ M1 and anti-inflammatory ‘alternative’ M2 macrophages, and their ratio is suggested to influence the metabolic complications of obesity. These macrophages derive primarily from peripheral blood mononuclear cells (PBMCs). We hypothesised that obesity and the metabolic syndrome modulate PBMC functions. Therefore, alteration of the monocyte response, and more specifically their ability to differentiate toward alternative anti-inflammatory macrophages, was assessed in PBMCs isolated from lean and obese subjects with or without alterations in glucose homeostasis. Our results indicate that PBMCs from obese subjects have an altered expression of M2 markers and that their monocytes are less susceptible to differentiate toward an alternative phenotype. Thus PBMCs in obesity are programmed, which may contribute to the inflammatory dysregulation and increased susceptibility to inflammatory diseases in these patients.

scholarly journals Associations between dietary patterns and gene expression pattern in peripheral blood mononuclear cells: a cross-sectional study

2020 ◽  
Author(s):  
Jacob J. Christensen ◽  
Stine M. Ulven ◽  
Magne Thoresen ◽  
Kenneth Westerman ◽  
Kirsten B. Holven ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Peripheral Blood Mononuclear Cells ◽  
Dietary Patterns ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Gene Clusters ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

AbstractBackgroundDiet may alter gene expression in immune cells involved in cardio-metabolic disease susceptibility. However, we still lack a robust understanding of the association between diet and immune cell-related gene expression in humans.ObjectiveOur objective was to examine the associations between dietary patterns (DPs) and gene expression profiles in peripheral blood mononuclear cells (PBMCs) in a population of healthy, Norwegian adults.MethodsWe used factor analysis to define a posteriori DPs from food frequency questionnaire-based dietary assessment data. In addition, we derived interpretable features from microarray-based gene expression data (13 967 transcripts) using two algorithms: CIBERSORT for estimation of cell subtype proportions, and weighted gene co-expression network analysis (WGCNA) for cluster discovery. Finally, we associated DPs with either CIBERSORT-predicted PBMC leukocyte distribution or WGCNA gene clusters using linear regression models. All analyses were gender-stratified (n = 130 women and 105 men).ResultsWe detected three DPs that broadly reflected Western, Vegetarian, and Low carbohydrate diets. CIBERSORT-predicted percentage of monocytes associated strongly and negatively with the Vegetarian DP in both women and men. For women, the Vegetarian DP associated most strongly with a large gene cluster consisting of 600 genes mainly involved in regulation of DNA transcription. For men, the Western DP inversely associated most strongly with a smaller cluster of 36 genes mainly involved in regulation of metabolic and inflammatory processes. In subsequent protein-protein interaction network analysis, the most important driver genes within these WGCNA gene clusters seemed to physically interact in biological networks.ConclusionsDPs may affect percentage monocytes and regulation of key biological processes within the PBMC pool. Although the present findings are exploratory, our analysis pipeline serves a useful framework for studying the association between diet and gene expression.

Gene expression of peripheral blood mononuclear cells is affected by cold exposure

2015 ◽  
Vol 309 (8) ◽  
pp. R824-R834 ◽  
Author(s):  
Bàrbara Reynés ◽  
Estefanía García-Ruiz ◽  
Paula Oliver ◽  
Andreu Palou
Keyword(s):  
Adipose Tissue ◽  
Peripheral Blood Mononuclear Cells ◽  
Cold Exposure ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Fat Depots ◽  
Brown Adipose ◽  
Blood Mononuclear Cells ◽  
Retroperitoneal White Adipose Tissue

Because of the discovery of brown adipose tissue (BAT) in humans, there is increased interest in the study of induction of this thermogenic tissue as a basis to combat obesity and related complications. Cold exposure is one of the strongest stimuli able to activate BAT and to induce the appearance of brown-like (brite) adipocytes in white fat depots (browning process). We analyzed the potential of peripheral blood mononuclear cells (PBMCs) to reflect BAT and retroperitoneal white adipose tissue (rWAT) response to 1-wk cold acclimation (4°C) at different ages of rat development (1, 2, 4, and 6 mo). As expected, cold exposure increased fatty acid β-oxidation capacity in BAT and rWAT (increased Cpt1a expression), explaining increased circulating nonesterified free fatty acids and decreased adiposity. Cold exposure increased expression of the key thermogenic gene, Ucp1, in BAT and rWAT, but only in 1-mo-old animals. Additionally, other brown/brite markers were affected by cold during the whole developmental period studied in BAT. However, in rWAT, cold exposure increased studied markers mainly at early age. PBMCs did not express Ucp1, but expressed other brown/brite markers, which were cold regulated. Of particular interest, PBMCs reflected adipose tissue-increased Cpt1a mRNA expression in response to cold (in older animals) and browning induction occurring in rWAT of young animals (1 mo) characterized by increased Cidea expression and by the appearance of a high number of multilocular CIDE-A positive adipocytes. These results provide evidence pointing to PBMCs as an easily obtainable biological material to be considered to perform browning studies with minimum invasiveness.

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