scholarly journals 11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

2013 ◽  
Vol 93 (3) ◽  
pp. 1139-1206 ◽  
Author(s):  
Karen Chapman ◽  
Megan Holmes ◽  
Jonathan Seckl
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Cells ◽  
Selective Inhibition ◽  
Adult Brain ◽  
Metabolic Complications ◽  
Intact Cells ◽  
Apparent Mineralocorticoid Excess ◽  
Human Therapy ◽  
Multiple Metabolic Syndrome ◽  
Glucocorticoid Action

Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

Innate immunity orchestrates adipose tissue homeostasis

2017 ◽  
Vol 31 (1) ◽  
Author(s):  
Yi-Wei Lin ◽  
Li-Na Wei
Keyword(s):  
Insulin Resistance ◽  
Innate Immunity ◽  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Whole Body ◽  
M2 Macrophage ◽  
Low Grade ◽  
Metabolic Complications ◽  
M1 Macrophage

AbstractObesity is strongly associated with multiple diseases including insulin resistance, type 2 diabetes, cardiovascular diseases, fatty liver disease, neurodegenerative diseases and cancers, etc. Adipose tissue (AT), mainly brown AT (BAT) and white AT (WAT), is an important metabolic and endocrine organ that maintains whole-body homeostasis. BAT contributes to non-shivering thermogenesis in a cold environment; WAT stores energy and produces adipokines that fine-tune metabolic and inflammatory responses. Obesity is often characterized by over-expansion and inflammation of WAT where inflammatory cells/mediators are abundant, especially pro-inflammatory (M1) macrophages, resulting in chronic low-grade inflammation and leading to insulin resistance and metabolic complications. Macrophages constitute the major component of innate immunity and can be activated as a M1 or M2 (anti-inflammatory) phenotype in response to environmental stimuli. Polarized M1 macrophage causes AT inflammation, whereas polarized M2 macrophage promotes WAT remodeling into the BAT phenotype, also known as WAT browning/beiging, which enhances insulin sensitivity and metabolic health. This review will discuss the regulation of AT homeostasis in relation to innate immunity.

scholarly journals Exploring the Cell Stemness and the Complexity of theAdipose Tissue Niche

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1906
Author(s):  
Nadav Kislev ◽  
Roza Izgilov ◽  
Raizel Adler ◽  
Dafna Benayahu
Keyword(s):  
Adipose Tissue ◽  
Immune Cells ◽  
Inflammatory Cells ◽  
Regulatory State ◽  
Metabolic Complications ◽  
Mesenchymal Progenitors ◽  
Stem And Progenitor Cells ◽  
Combination Of Methods

Adipose tissue is a complex organ composed of different cellular populations, including mesenchymal stem and progenitor cells, adipocytes, and immune cells such as macrophages and lymphocytes. These cellular populations alter dynamically during aging or as a response to pathophysiology such as obesity. Changes in the various inflammatory cells are associated with metabolic complications and the development of insulin resistance, indicating that immune cells crosstalk with the adipocytes. Therefore, a study of the cell populations in the adipose tissue and the extracellular matrix maintaining the tissue niche is important for the knowledge on the regulatory state of the organ. We used a combination of methods to study various parameters to identify the composition of the resident cells in the adipose tissue and evaluate their profile. We analyzed the tissue structure and cells based on histology, immune fluorescence staining, and flow cytometry of cells present in the tissue in vivo and these markers’ expression in vitro. Any shift in cells’ composition influences self-renewal of the mesenchymal progenitors, and other cells affect the functionality of adipogenesis.

scholarly journals Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and impairs glucose tolerance in lean mice

2021 ◽  
pp. 101225
Author(s):  
Rachel Bell ◽  
Elisa Villalobos ◽  
Mark Nixon ◽  
Allende Miguelez-Crespo ◽  
Lee Murphy ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Carbonyl Reductase ◽  
Glucocorticoid Action

Expression of genes related to glucocorticoid action in human subcutaneous and omental adipose tissue

2010 ◽  
Vol 122 (1-3) ◽  
pp. 28-34 ◽  
Author(s):  
Alain Veilleux ◽  
Philippe Y. Laberge ◽  
Jacques Morency ◽  
Suzanne Noël ◽  
Van Luu-The ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Omental Adipose Tissue ◽  
Expression Of Genes ◽  
Glucocorticoid Action

Inflammation and impaired adipogenesis in hypertrophic obesity in man

2009 ◽  
Vol 297 (5) ◽  
pp. E999-E1003 ◽  
Author(s):  
Birgit Gustafson ◽  
Silvia Gogg ◽  
Shahram Hedjazifar ◽  
Lachmi Jenndahl ◽  
Ann Hammarstedt ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Preadipocyte Differentiation ◽  
Metabolic Complications ◽  
Adipose Cell ◽  
Subcutaneous Adipose ◽  
Adipose Cell Size

Obesity is associated mainly with adipose cell enlargement in adult man (hypertrophic obesity), whereas the formation of new fat cells (hyperplastic obesity) predominates in the prepubertal age. Adipose cell size, independent of body mass index, is negatively correlated with whole body insulin sensitivity. Here, we review recent findings linking hypertrophic obesity with inflammation and a dysregulated adipose tissue, including local cellular insulin resistance with reduced IRS-1 and GLUT4 protein content. In addition, the number of preadipocytes in the abdominal subcutaneous adipose tissue capable of undergoing differentiation to adipose cells is reduced in hypertrophic obesity. This is likely to promote ectopic lipid accumulation, a well-known finding in these individuals and one that promotes insulin resistance and cardiometabolic risk. We also review recent results showing that TNFα, but not MCP-1, resistin, or IL-6, completely prevents normal adipogenesis in preadipocytes, activates Wnt signaling, and induces a macrophage-like phenotype in the preadipocytes. In fact, activated preadipocytes, rather than macrophages, may completely account for the increased release of chemokines and cytokines by the adipose tissue in obesity. Understanding the molecular mechanisms for the impaired preadipocyte differentiation in the subcutaneous adipose tissue in hypertrophic obesity is a priority since it may lead to new ways of treating obesity and its associated metabolic complications.

scholarly journals Puerarin Attenuates Obesity-Induced Inflammation and Dyslipidemia by Regulating Macrophages and TNF-Alpha in Obese Mice

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 175
Author(s):  
Ji-Won Noh ◽  
Hee-Kwon Yang ◽  
Min-Soo Jun ◽  
Byung-Cheol Lee
Keyword(s):  
Adipose Tissue ◽  
In Silico ◽  
Tolerance Test ◽  
Low Grade ◽  
Adipocyte Size ◽  
Metabolic Complications ◽  
Immunological Mechanisms ◽  
Tnf Α ◽  
Test Serum

Obesity causes low-grade inflammation that results in dyslipidemia and insulin resistance. We evaluated the effect of puerarin on obesity and metabolic complications both in silico and in vivo and investigated the underlying immunological mechanisms. Twenty C57BL/6 mice were divided into four groups: normal chow, control (HFD), HFD + puerarin (PUE) 200 mg/kg, and HFD + atorvastatin (ATO) 10 mg/kg groups. We examined bodyweight, oral glucose tolerance test, serum insulin, oral fat tolerance test, serum lipids, and adipocyte size. We also analyzed the percentage of total, M1, and M2 adipose tissue macrophages (ATMs) and the expression of F4/80, tumor necrosis factor-α (TNF-α), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, and C-X-C motif chemokine receptor 4. In silico, we identified the treatment-targeted genes of puerarin and simulated molecular docking with puerarin and TNF, M1, and M2 macrophages based on functionally enriched pathways. Puerarin did not significantly change bodyweight but significantly improved fat pad weight, adipocyte size, fat area in the liver, free fatty acids, triglycerides, total cholesterol, and HDL-cholesterol in vivo. In addition, puerarin significantly decreased the ATM population and TNF-α expression. Therefore, puerarin is a potential anti-obesity treatment based on its anti-inflammatory effects in adipose tissue.

scholarly journals Inflammatory cells in perivascular adipose tissue and the integrity of the tunica media in atherosclerotic coronary arteries

2019 ◽  
Author(s):  
Ruda Zorc-Pleskovič ◽  
Marjeta Zorc ◽  
Dušan Šuput ◽  
Aleksandra Milutinović
Keyword(s):  
Adipose Tissue ◽  
Coronary Arteries ◽  
Obstructive Coronary Artery Disease ◽  
Inflammatory Cells ◽  
Elastic Membrane ◽  
Inflammatory Infiltration ◽  
Perivascular Adipose Tissue ◽  
Tunica Media ◽  
External Elastic Membrane ◽  
The Media

Obstructive coronary artery disease (CAD) is characterized by inflammation within the atherosclerotic coronary arteries. Infiltration of inflammatory cells into muscular media can lead to remodeling and weakening of the arterial wall. We examined the relationship between inflammatory infiltration in perivascular adipose tissue (PVAT), state of the external elastic membrane, and the intensity of inflammatory infiltration in the tunica media of coronary arteries obtained by endarterectomy from symptomatic patients with diffuse CAD. We analyzed endarterectomy sequesters from 22 coronary arteries that contained the intima, media, a part of the adventitia, and PVAT in at least one part of the sequester. The coronary arteries were divided into two groups according to the presence or absence of inflammatory infiltration in PVAT. Staining with hematoxylin-eosin and by the Movat's method showed atherosclerotic changes in the intima and media. Immunohistochemistry (anti-leukocyte common antigen [LCA] antibody) was used for the detection of leukocytes. We found a significant positive correlation between inflammatory infiltration in PVAT and preservation of the external elastic membrane of coronary arteries. Furthermore, we found a significant negative correlation between inflammatory infiltration in PVAT and the intensity of inflammatory infiltration in the media. It seems that the integrity of the external elastic membrane and the proinflammatory properties of PVAT restrain inflammatory cells within PVAT. Both effects may prevent the migration of inflammatory cells into the media and delay the development of CAD.

Dietary carbohydrates as a means to prevent obesity and adipose tissue inflammation

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Ellen Vercalsteren ◽  
Christine Vranckx ◽  
Liesbeth Frederix ◽  
Max Gooijen ◽  
Ilse Scroyen
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Adipose Tissue ◽  
Plasma Cholesterol ◽  
Inflammatory Cells ◽  
Mannose Receptor ◽  
Foxp3 Expression ◽  
Blood Stream ◽  
Dietary Carbohydrates ◽  
High Fructose

AbstractWhen obesity arises, adipose tissue (AT) expands and shifts to an influx of pro-inflammatory cells, leading to a state of chronic AT-inflammation.Furthermore, a western diet (WD) modulates the gut microbiome, increasing intestinal permeability. This facilitates the translocation of endotoxins and even entire bacteria into the blood stream, further contributing to the pro-inflammatory state. Even though it is evident a WD, high in fat and carbohydrates (CHO), can cause AT-inflammation, it is still unclear if fat or CHO is the main inducer. Therefore, we are currently investigating the effect of different CHO-types on AT-inflammation.During 15 weeks, male C57BL/6JRj mice were kept on several diets, consisting of high-fructose (HFRD), high-sucrose-high-fructose (HCFD), high-starch (HSTD) or a WD (n = 10 per group). Weekly monitoring of body weight and food intake was followed by analyses of visceral AT-inflammation. Kruskal-wallis tests were used for statistical analysis.Mice on HSTD and HCD had gained significantly less body weight compared to mice on WD after 15 weeks of diet. Mice on HSTD also gained significantly less body weight compared to mice on HFRD and HCFD. Moreover, mice on HSTD and HCD also had significantly smaller AT-depots as compared to mice on WD. Total plasma cholesterol as well as HDL and LDL levels were significantly lower in mice on HSTD and on HCD as compared to mice on WD. Gene expression analysis revealed a significantly lower expression of several pro-inflammatory markers (F4/80, Arg1, Mannose receptor, TNF, MCP1 and Saa3) in AT of mice on HSTD and on HCD compared to a WD. A HSTD also induced lower AT-expression of MCP1 and Saa3 than a HCFD and Saa3 expression was also significantly lower in the HSTD-group compared to the HFRD-group. Furthermore, Foxp3 expression, a marker for anti-inflammatory Treg cells, was significantly increased in AT of all CHO-diet fed mice as compared to the WD-group.In conclusion, these data suggest that certain dietary carbohydrates, in contrast to a WD, do not induce obesity or AT-inflammation, including lower gene expression of Saa3. It is stated that a WD induces Saa3 expression not only in AT, but also in the colon. Furthermore, since Saa3 is able to bind bacteria and is associated with inflammation, further research is necessary to investigate Saa3 as a possible link between disturbances in the gut microbiota and AT-inflammation.

scholarly journals Regulation of Na+ transport in brown adipose tissue

1986 ◽  
Vol 235 (2) ◽  
pp. 545-552 ◽  
Author(s):  
K F LaNoue ◽  
C Koch ◽  
D Strzelecka ◽  
T P Kobylski
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Membrane Vesicle ◽  
Membrane Vesicles ◽  
Fat Cell ◽  
Isolated Cells ◽  
Intact Cells ◽  
Dependent Atpase ◽  
Brown Adipose ◽  
Active Transport System

In order to test the hypothesis that Na+, K+-ATPase (Na+,K+-dependent ATPase) is involved in the noradrenaline-mediated stimulation of respiration in brown adipose tissue, the effects of noradrenaline on Na+,K+-ATPase in isolated brown-fat-cell membrane vesicles, and on 22Na+ and K+ (86Rb+) fluxes across the membranes of intact isolated cells, were measured. The ouabain-sensitive fraction of the K+-dependent ATPase activity in the isolated membrane-vesicle preparation was small and was not affected by the presence of noradrenaline in the incubation media. The uptake of 86Rb+ into intact hormone-sensitive cells was inhibited by 80% by ouabain, but it was insensitive to the presence of noradrenaline. 22Na+ uptake and efflux measured in the intact cells were 8 times more rapid than the 86Rb+ fluxes and were unaffected by ouabain. This indicated the presence of a separate, more active, transport system for Na+ than the Na+,K+-ATPase. This is likely to be a Na+/Na+ exchange activity under normal aerobic conditions. However, under anaerobic conditions, or conditions simulating anaerobiosis (2 mM-NaCN), the unidirectional uptake of Na+ increased dramatically, while efflux was unaltered.

Fructose consumption enhances glucocorticoid action in rat visceral adipose tissue

2013 ◽  
Vol 24 (6) ◽  
pp. 1166-1172 ◽  
Author(s):  
Biljana N. Bursać ◽  
Ana D. Djordjevic ◽  
Ana D. Vasiljević ◽  
Danijela D. Vojnović Milutinović ◽  
Nataša A. Veličković ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Visceral Adipose ◽  
Glucocorticoid Action
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