scholarly journals Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1403 ◽  
Author(s):  
Gema Frühbeck ◽  
Inmaculada Balaguer ◽  
Leire Méndez-Giménez ◽  
Víctor Valentí ◽  
Sara Becerril ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Er Stress ◽  
Subcutaneous Fat ◽  
Subcellular Fractionation ◽  
Normal Weight ◽  
Compensatory Mechanism ◽  
Tissue Samples ◽  
Water Glycerol ◽  
Tgf Β1

Aquaporin-11 (AQP11) is expressed in human adipocytes, but its functional role remains unknown. Since AQP11 is an endoplasmic reticulum (ER)-resident protein that transports water, glycerol, and hydrogen peroxide (H2O2), we hypothesized that this superaquaporin is involved in ER stress induced by lipotoxicity and inflammation in human obesity. AQP11 expression was assessed in 67 paired visceral and subcutaneous adipose tissue samples obtained from patients with morbid obesity and normal-weight individuals. We found that obesity and obesity-associated type 2 diabetes increased (p < 0.05) AQP11 mRNA and protein in visceral adipose tissue, but not subcutaneous fat. Accordingly, AQP11 mRNA was upregulated (p < 0.05) during adipocyte differentiation and lipolysis, two biological processes altered in the obese state. Subcellular fractionation and confocal microscopy studies confirmed its presence in the ER plasma membrane of visceral adipocytes. Proinflammatory factors TNF-α, and particularly TGF-β1, downregulated (p < 0.05) AQP11 mRNA and protein expression and reinforced its subcellular distribution surrounding lipid droplets. Importantly, the AQP11 gene knockdown increased (p < 0.05) basal and TGF-β1-induced expression of the ER markers ATF4 and CHOP. Together, the downregulation of AQP11 aggravates TGF-β1-induced ER stress in visceral adipocytes. Owing to its “peroxiporin” properties, AQP11 overexpression in visceral fat might constitute a compensatory mechanism to alleviate ER stress in obesity.

scholarly journals Different Expression of Mitochondrial and Endoplasmic Reticulum Stress Genes in Epicardial Adipose Tissue Depends on Coronary Atherosclerosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4538
Author(s):  
Helena Kratochvílová ◽  
Miloš Mráz ◽  
Barbora J. Kasperová ◽  
Daniel Hlaváček ◽  
Jakub Mahrík ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Cardiac Surgery ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Mrna Expression ◽  
Coronary Atherosclerosis ◽  
Stress Genes ◽  
Valvular Surgery

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.

scholarly journals Acute Tissue Injury Caused by Subcutaneous Fat Biopsies Produces Endoplasmic Reticulum Stress

2009 ◽  
Vol 30 (7) ◽  
pp. 928-928
Author(s):  
Guenther Boden ◽  
Matthew Silviera ◽  
Brian Smith ◽  
Peter Cheung ◽  
Carol Homko
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Tissue Injury ◽  
Subcutaneous Fat ◽  
Whole Body ◽  
Monocyte Chemoattractant Protein 1 ◽  
Homologous Protein ◽  
Stress Markers ◽  
Acute Tissue Injury ◽  
Glucose Regulated Protein

Abstract Background It is not known whether acute tissue injury is associated with endoplasmic reticulum (ER) stress. Objective Our objective was to determine whether open, sc fat biopsies cause ER stress. Approach Five healthy subjects underwent three open sc fat biopsies. The first biopsy, taken from the lateral aspect of a thigh, was followed 4 h later by a second biopsy from the same incision site and a third biopsy from the contralateral leg. Expression markers of ER stress, inflammation, hypoxia, and adipokines were measured in these fat biopsies. In addition, we tested for signs of systemic ER stress and inflammation in plasma and in circulating monocytes. Results mRNA/18s ratios of IL-6, monocyte chemoattractant protein-1, CD-14, hypoxia-induced factor 1-α, the spliced form of Xbox protein-1, glucose-regulated protein 78, CEBP homologous protein, and activating factor-4 were all severalfold higher, whereas mRNA/18s ratios of adiponectin and leptin were lower in fat biopsies taken from the same site 4 h after the first biopsy but were unchanged in the second biopsy that was taken from the contralateral site. The biopsies were not associated with changes in plasma and monocyte IL-6 concentrations or in monocyte ER stress markers. Also, whole-body insulin-stimulated glucose uptake was the same in 15 subjects who had biopsies compared with 15 different subjects who did not. Conclusion Open, sc fat biopsies produced inflammation, hypoxia, ER stress, and decreased expression of adiponectin and leptin. These changes remained confined to the biopsy site for at least 4 h.

Mitochondria-associated ER membranes in glucose homeostasis and insulin resistance

2020 ◽  
Vol 319 (6) ◽  
pp. E1053-E1060
Author(s):  
Logan K. Townsend ◽  
Henver S. Brunetta ◽  
Marcelo A. S. Mori
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Glucose Homeostasis ◽  
Calcium Homeostasis ◽  
Adenine Nucleotides ◽  
Current Controversy

Obesity and insulin resistance (IR) are associated with endoplasmic reticulum (ER) stress and mitochondrial dysfunction in several tissues. Although for many years mitochondrial and ER function were studied separately, these organelles also connect to produce interdependent functions. Communication occurs at mitochondria-associated ER membranes (MAMs) and regulates lipid and calcium homeostasis, apoptosis, and the exchange of adenine nucleotides, among other things. Recent evidence suggests that MAMs contribute to organelle, cellular, and systemic metabolism. In obesity and IR models, metabolic tissues such as the liver, skeletal muscle, pancreas, and adipose tissue present alterations in MAM structure or function. The purpose of this mini review is to highlight the MAM disruptions that occur in each tissue during obesity and IR and its relationship with glucose homeostasis and IR. We also discuss the current controversy that surrounds MAMs’ role in the development of IR.

scholarly journals TGF-β1 Activates Nasal Fibroblasts through the Induction of Endoplasmic Reticulum Stress

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 942
Author(s):  
Jae-Min Shin ◽  
Ju-Hyung Kang ◽  
Joo-Hoo Park ◽  
Hyun-Woo Yang ◽  
Heung-Man Lee ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Inflammatory Diseases ◽  
Upper Airway ◽  
Tissue Remodeling ◽  
Organ Cultures ◽  
Stress Marker ◽  
Stress Markers ◽  
Collagen Contraction ◽  
Tgf Β1

(1) Background: Tissue remodeling and extracellular matrix (ECM) accumulation contribute to the development of chronic inflammatory diseases of the upper airway. Endoplasmic reticulum (ER) stress is considered to be the key signal for triggering tissue remodeling in pathological conditions. The present study aimed to investigate the role of ER-stress in TGF-β1-stimulated nasal fibroblasts and inferior turbinate organ cultures; (2) Methods: Fibroblasts and organ cultures were pretreated with 4-phenylbutyric acid (PBA) and stimulated with TGF-β1 or thapsigargin (TG). Expression of ER-stress markers, myofibroblast marker, and ECM components was measured by Western blotting and real-time PCR. Reactive oxygen species (ROS) were quantified using 2′,7′-dichlorofluorescein diacetate. Cell migration was evaluated using Transwell assays. Contractile activity was measured by collagen contraction assay; (3) Results: 4-PBA inhibited TGF-β1 or TG-induced ER-stress marker expression, phenotypic changes, and ECM. Pre-treatment with ROS scavengers inhibited the expression of TGF-β1-induced ER-stress markers. Migration and collagen contraction of TGF-β1 or TG-stimulated fibroblasts were ameliorated by 4-PBA treatment. These findings were confirmed in ex vivo organ cultures; (4) Conclusions: 4-PBA downregulates TGF-β1-induced ER-stress marker expression, migration, and collagen contraction via ROS in fibroblasts and organ cultures. These results suggest that ER-stress may play an important role in progression of chronic upper airway inflammatory diseases by aiding pathological tissue remodeling.

scholarly journals Endoplasmic Reticulum Stress in Subepithelial Myofibroblasts Increases the TGF-β1 Activity That Regulates Fibrosis in Crohn’s Disease

2020 ◽  
Vol 26 (6) ◽  
pp. 809-819 ◽  
Author(s):  
Chao Li ◽  
John R Grider ◽  
Karnam S Murthy ◽  
Jaime Bohl ◽  
Emily Rivet ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Direct Interaction ◽  
Binding Activity ◽  
Luciferase Reporter ◽  
Stress Components ◽  
Tgf Β1

Abstract Background Endoplasmic reticulum (ER) stress is an essential response of epithelial and immune cells to inflammation in Crohn’s disease. The presence and mechanisms that might regulate the ER stress response in subepithelial myofibroblasts (SEMFs) and its role in the development of fibrosis in patients with Crohn’s disease have not been examined. Methods Subepithelial myofibroblasts were isolated from the affected ileum and normal ileum of patients with each Montreal phenotype of Crohn’s disease and from normal ileum in non-Crohn’s subjects. Binding of GRP78 to latent TGF-β1 and its subcellular trafficking was examined using proximity ligation-hybridization assay (PLA). The effects of XBP1 and ATF6 on TGF-β1 expression were measured using DNA-ChIP and luciferase reporter assay. Endoplasmic reticulum stress components, TGF-β1, and collagen levels were analyzed in SEMF transfected with siRNA-mediated knockdown of DNMT1 and GRP78 or with DNMT1 inhibitor 5-Azacytidine or with overexpression of miR-199a-5p. Results In SEMF of strictured ileum from patients with B2 Crohn’s disease, expression of ER stress sensors increased significantly. Tunicamycin elicited time-dependent increase in GRP78 protein levels, direct interaction with latent TGF-β1, and activated TGF-β1 signaling. The TGFB1 DNA-binding activity of ATF-6α and XBP1 were significantly increased and elicited increased TGFB1 transcription in SEMF-isolated from affected ileum. The levels of ER stress components, TGF-β1, and collagen expression in SEMF were significantly decreased following knockdown of DNMT1 or GRP78 by 5-Azacytidine treatment or overexpression of miR-199a-5p. Conclusions Endoplasmic reticulum stress is present in SEMF of patients susceptible to fibrostenotic Crohn’s disease and can contribute to development of fibrosis. Targeting ER stress may represent a novel therapeutic target to prevent fibrosis in patients with fibrostenotic Crohn’s disease.

scholarly journals The effect of royal jelly and tocotrienol-rich fraction along with calorie restriction on hypothalamic endoplasmic reticulum stress and adipose tissue inflammation in diet-induced obese rats

2020 ◽  
Author(s):  
Pardis Irandoost ◽  
Naimeh Mesri Alamdari ◽  
Atoosa Saidpour ◽  
Farzad Shidfar ◽  
Farnaz Farsi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Er Stress ◽  
Calorie Restriction ◽  
Inflammatory Markers ◽  
Royal Jelly ◽  
Adipose Tissue Inflammation ◽  
Adipose Tissue Dysfunction ◽  
Obese Rats ◽  
Tocotrienol Rich Fraction

Abstract Objectives: Endoplasmic reticulum (ER) stress causes adipose tissue dysfunction and chronic inflammation in obesity. Royal jelly (RJ) and tocotrienol-rich fraction (TRF) are reported to ameliorate inflammation. However, the improving effects of RJ and TRF on inflammation from ER stress modulating view have not been assessed so far. Hence, we investigated the effect of RJ and TRF on ER stress and some adipose tissue-derived inflammatory markers in the high-fat diet (HFD)-induced obesity. Wistar obese rats randomly allocated into 5 groups: HFD, calorie restriction diet (CRD), RJ+CRD, TRF+CRD, RJ+TRF+CRD. After 8-week intervention, adipose tissues and hypothalamus were dissected and serum was collected. Results: RJ reduced glucose-regulated protein-78 (GRP78) expression as ER stress indicator in WAT and hypothalamus compared to CRD. Besides, RJ diminished the expression of inflammatory markers in white adipose tissue (WAT) and also decreased the serum concentration of them. TRF reduced inflammatory markers in the serum without remarkable effects on ER stress. Overall, RJ has protective effect against adipose tissue dysfunction and inflammation then suggested as a therapeutic approach to reduce some obesity-related complications. The impact of TRF in this regard is lower than RJ and limited to systemic inflammation improvement without remarkable changes in adipose tissue inflammation.

scholarly journals Fibroblast growth factor 21 reverses suppression of adiponectin expression via inhibiting endoplasmic reticulum stress in adipose tissue of obese mice

2016 ◽  
Vol 242 (4) ◽  
pp. 441-447 ◽  
Author(s):  
Qinyue Guo ◽  
Lin Xu ◽  
Jiali Liu ◽  
Huixia Li ◽  
Hongzhi Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Growth Factor ◽  
Er Stress ◽  
Insulin Signaling ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Obese Mice

Fibroblast growth factor 21 (FGF21) has recently emerged as a novel endocrine hormone involved in the regulation of glucose and lipid metabolism. However, the exact mechanisms whereby FGF21 mediates insulin sensitivity remain not fully understood. In the present study, FGF21was administrated in high-fat diet-induced obese mice and tunicamycin-induced 3T3-L1 adipocytes, and metabolic parameters, endoplasmic reticulum (ER) stress indicators, and insulin signaling molecular were assessed by Western blotting. The administration of FGF21 in obese mice reduced body weight, blood glucose and serum insulin, and increased insulin sensitivity, resulting in alleviation of insulin resistance. Meanwhile, FGF21 treatment reversed suppression of adiponectin expression and restored insulin signaling via inhibiting ER stress in adipose tissue of obese mice. Additionally, suppression of ER stress via the ER stress inhibitor tauroursodeoxycholic acid increased adiponectin expression and improved insulin resistance in obese mice and in tunicamycin-induced adipocytes. In conclusion, our results showed that the administration of FGF21 reversed suppression of adiponectin expression and restored insulin signaling via inhibiting ER stress under the condition of insulin resistance, demonstrating the causative role of ER stress in downregulating adiponectin levels.

scholarly journals Role of microRNA 690 in Mediating Angiotensin II Effects on Inflammation and Endoplasmic Reticulum Stress

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1327
Author(s):  
Kalhara R. Menikdiwela ◽  
Latha Ramalingam ◽  
Mostafa M. Abbas ◽  
Halima Bensmail ◽  
Shane Scoggin ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Angiotensin Ii ◽  
Er Stress ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Small Rna Sequencing ◽  
Ang Ii ◽  
Protective Function

Overactivation of the renin–angiotensin system (RAS) during obesity disrupts adipocyte metabolic homeostasis and induces endoplasmic reticulum (ER) stress and inflammation; however, underlying mechanisms are not well known. We propose that overexpression of angiotensinogen (Agt), the precursor protein of RAS in adipose tissue or treatment of adipocytes with Angiotensin II (Ang II), RAS bioactive hormone, alters specific microRNAs (miRNA), that target ER stress and inflammation leading to adipocyte dysfunction. Epididymal white adipose tissue (WAT) from B6 wild type (Wt) and transgenic male mice overexpressing Agt (Agt-Tg) in adipose tissue and adipocytes treated with Ang II were used. Small RNA sequencing and microarray in WAT identified differentially expressed miRNAs and genes, out of which miR-690 and mitogen-activated protein kinase kinase 3 (MAP2K3) were validated as significantly up- and down-regulated, respectively, in Agt-Tg, and in Ang II-treated adipocytes compared to respective controls. Additionally, the direct regulatory role of miR-690 on MAP2K3 was confirmed using mimic, inhibitors and dual-luciferase reporter assay. Downstream protein targets of MAP2K3 which include p38, NF-κB, IL-6 and CHOP were all reduced. These results indicate a critical post-transcriptional role for miR-690 in inflammation and ER stress. In conclusion, miR-690 plays a protective function and could be a useful target to reduce obesity.

scholarly journals Plant Bioactive Molecules Reduces Endoplasmic Reticulum Stress in Liver and Adipose Tissue of Obese Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 482-482
Author(s):  
Ivan Torre-Villalvazo ◽  
Armando Tovar ◽  
Claudia Tovar-Palacio ◽  
Nimbe Torres ◽  
Erik Alejandro Torre ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Low Dose ◽  
Control Diet ◽  
Bioactive Molecules ◽  
Obese Mice ◽  
Funding Sources ◽  
Stress Markers

Abstract Objectives To determine if diferent plant bioactive compounds can ammelirate endoplasmic reticulum stress markers in liver and adipose tissue of obese mice and mice administered with a low dose of tunicamicin. Methods C57BL6 mice were fed a control diet (7% fat) or a high-fat diet (21% fat) with and without genistein or resveratrol supplementation (0.1%) for 12 weeks. Pharmacologic ER stress was induced in mice fed the control diet by an ip injection of a low dose of tunicamycin and euthanized 8 or 24 h after tunicamycin administration. Adipose tissues and liver were harvested to determine the abundance of ER stress markers by western blot and real time PCR. Results Genistein and resveratrol reduced the abundance of phospho JNK and phospho PERK in liver and subcutaneous adipose tissue of obese mice and lean mice administered with tunicamycin. Both polyphenols increased the mRNA abundance of XBP1s and BiP and reduced that of CHOP in both organs. These changes in proten phosphorylation and gene expression were accompanied with reduced hepatic steatosis and adipocyte hypertrophy. Conclusions The supplementation with plant polyphenols such as genistein or resveratrol reduced ER stress markers in liver and adipose tissue of obese mice and lean mice administerd with tunicamycin. Funding Sources This work is supported by a grant from CONACYT, Mexico to ITV Grant No. A1-S-41,077.

scholarly journals Comparative Analysis of Mesenchymal Stromal Cells Biological Properties

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Angela De Luca ◽  
Rosanna Verardi ◽  
Arabella Neva ◽  
Patrizia Benzoni ◽  
Elisabetta Crescini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Subcutaneous Fat ◽  
Biological Properties ◽  
Human Mscs ◽  
Differentiation Potential ◽  
Tissue Samples

The stromal progenitors of mesodermal cells, mesenchymal stromal cells (MSCs), are a heterogeneous population of plastic adherent fibroblast-like cells with extensive proliferative capacity and differentiation potential. Human MSCs have now been isolated from various tissues including bone marrow, muscle, skin, and adipose tissue, the latter being one of the most suitable cell sources for cell therapy, because of its easy accessibility, minimal morbidity, and abundance of cells. Bone marrow and subcutaneous or visceral adipose tissue samples were collected, digested with collagenase if needed, and seeded in Iscove's medium containing 5% human platelet lysate. Nonadherent cells were removed after 2-3 days and the medium was replaced twice a week. Confluent adherent cells were detached, expanded, and analyzed for several biological properties such as morphology, immunophenotype, growth rate, senescence, clonogenicity, differentiation capacity, immunosuppression, and secretion of angiogenic factors. The results show significant differences between lines derived from subcutaneous fat compared to those derived from visceral fat, such as the higher proliferation rate of the first and the strong induction of angiogenesis of the latter. We are convinced that the identification of the peculiarities of MSCs isolated from different tissues will lead to their more accurate use in cell therapy.

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