scholarly journals Pathways regulated by glucocorticoids in omental and subcutaneous human adipose tissues: a microarray study

2011 ◽  
Vol 300 (3) ◽  
pp. E571-E580 ◽  
Author(s):  
Mi-Jeong Lee ◽  
Da-Wei Gong ◽  
Bryan F. Burkey ◽  
Susan K. Fried
Keyword(s):  
Adipose Tissue ◽  
Transcription Factors ◽  
Gene Networks ◽  
Human Adipose Tissue ◽  
Endocrine Function ◽  
Upper Body ◽  
Adipose Tissues ◽  
Severely Obese ◽  
Fat Stores ◽  
Upregulated Genes

Glucocorticoids (GC) are powerful regulators of adipocyte differentiation, metabolism, and endocrine function and promote the development of upper body obesity, especially visceral fat stores. To provide a comprehensive understanding of how GC affect adipose tissue and adipocyte function, we analyzed patterns of gene expression (HG U95 Affymetrix arrays) after culture of abdominal subcutaneous (Abd sc) and omental (Om) adipose tissues from severely obese subjects (3 F, 1 M) in the presence of insulin or insulin (7 nM) plus dexamethasone (Dex, 25 nM) for 7 days. About 20% (561 genes in Om and 569 genes in sc) of 2,803 adipose expressed genes were affected by long-term GC. While most of the genes (90%) were commonly regulated by Dex in both depots, 26 in Om and 34 in Abd sc were affected by Dex in only one depot. 60% of the commonly upregulated genes were involved in metabolic pathways and were expressed mainly in adipocytes. Dex suppressed genes in immune/inflammatory (IL-6, IL-8, and MCP-1, expressed in nonadipocytes) and proapoptotic pathways, yet induced genes related to the acute-phase response (SAA, factor D, haptoglobin, and RBP4, expressed in adipocytes) and stress/defense response. Functional classification analysis showed that Dex also induced expression levels of 22 transcription factors related to insulin action and lipogenesis (LXRα, STAT5α, SREBP1, and FoxO1) and immunity/adipogenesis (TSC22D3) while suppressing 17 transcription factors in both depots. Overall, these studies reveal the powerful effects of GC on gene networks that regulate many key functions in human adipose tissue.

scholarly journals Expression profiling of 11β-hydroxysteroid dehydrogenase type-1 and glucocorticoid-target genes in subcutaneous and omental human preadipocytes

2006 ◽  
Vol 37 (2) ◽  
pp. 327-340 ◽  
Author(s):  
I J Bujalska ◽  
M Quinkler ◽  
J W Tomlinson ◽  
C T Montague ◽  
D M Smith ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Target Genes ◽  
Adipocyte Differentiation ◽  
Human Adipose Tissue ◽  
Fat Accumulation ◽  
Visceral Fat Accumulation ◽  
Human Preadipocytes ◽  
Upregulated Genes ◽  
Microarray Technique

Obesity is associated with increased morbidity and mortality from cardiovascular disease, diabetes and cancer. Although obesity is a multi-factorial heterogeneous condition, fat accumulation in visceral depots is most highly associated with these risks. Pathological glucocorticoid excess (i.e. in Cushing’s syndrome) is a recognised, reversible cause of visceral fat accumulation. The aim of this study was to identify depot-specific glucocorticoid-target genes in adipocyte precursor cells (preadipocytes) using Affymetrix microarray technique. Confluent preadipocytes from subcutaneous (SC) and omental (OM) adipose tissue collected from five female patients were treated for 24 h with 100 nM cortisol (F), RNA was pooled and hybridised to the Affymetrix U133 microarray set. We identified 72 upregulated and 30 downregulated genes by F in SC cells. In OM preadipocytes, 56 genes were increased and 19 were decreased. Among the most interesting were transcription factors, markers of adipocyte differentiation and glucose metabolism, cell adhesion and growth arrest protein factors involved in G-coupled and Wnt signalling. The Affymetrix data have been confirmed by quantitative real-time PCR for ten specific genes, including HSD11B1, GR, C/EBPα, C/EBPβ, IL-6, FABP4, APOD, IRS2, AGTR1 and GHR. One of the most upregulated genes in OM but not in SC cells was HSD11B1. The GR was similarly expressed and not regulated by glucocorticoids in SC and OM human preadipocytes. C/EBPα was expressed in SC preadipocytes and upregulated by F, but was below the detection level in OM cells. C/EBPβ was highly expressed both in SC and in OM preadipocytes, but was not regulated by F. Our results provide insight into the genes involved in the regulation of adipocyte differentiation by cortisol, highlighting the depot specifically in human adipose tissue.

Regional differences and up-regulation of progesterone receptors in adipose tissues from oestrogen-treated sheep

1996 ◽  
Vol 148 (1) ◽  
pp. 19-25 ◽  
Author(s):  
J S Mayes ◽  
J P McCann ◽  
T C Ownbey ◽  
G H Watson
Keyword(s):  
Adipose Tissue ◽  
Sex Steroids ◽  
Sucrose Gradient ◽  
Metabolic Diseases ◽  
Specific Binding ◽  
Regional Distribution ◽  
Upper Body ◽  
Adipose Tissues ◽  
Oestrogen Treatment ◽  
Omental Adipose Tissue

Abstract Differing risk factors between men and women for a number of vascular and metabolic diseases have been linked to regional obesity. The differences in the distribution of adipose tissues between men (abdominal or upper-body obesity) and women (gluteal/femoral or lower body obesity) suggest a role for sex steroids in the regional distribution of fat. Previous work from this laboratory has shown the presence of oestrogen receptor (ER) in gluteal, perirenal and omental adipose tissues of ewes with similar physical characteristics to the ER in uterine tissue. The concentration profile for adipose ER was gluteal> perirenal>omental. In this report, we determined the physiological significance of adipose ERs by showing an up-regulation of the progesterone receptor (PR) in adipose tissues after oestrogen treatment in a fashion similar to that seen in a major responsive tissue such as uterus. Using PR antibodies (PR-6 and C-262), Western blot analysis of PR from oestrogen-treated sheep indicated that PR was induced in uterus>>>gluteal adipose>perirenal adipose consistent with the concentration of ER contained in these tissues. PR could not be detected by Western blotting in omental adipose tissue from oestrogen-treated animals or in gluteal, perirenal and omental adipose tissues from untreated animals. Sucrose gradient profiles of progestin (R-5020) binding from uterus and gluteal adipose tissues of oestrogen-treated ewes showed specific binding in both the 5S and 9S regions of the gradient, while perirenal and omental adipose tissue had only the 5S peak. The amount of specific binding was increased with oestrogen treatment in all the tissues. When gluteal adipose tissue cytosol was preincubated with PR antibody (C-262) to prevent binding of ligand and subjected to sucrose gradient analysis, both the 5S and 9S regions were diminished, suggesting that both peaks contained PR. Dilution of uterine cytosol resulted in an increase in the ratio of the 5S to the 9S peak, indicating that the 9S PR complex dissociates at low concentrations; this may be the reason why only the 5S peak was observed in perirenal and omental adipose tissues. These data offer further support for a direct role of sex steroids in regional adipose accretion and metabolism. Journal of Endocrinology (1996) 148, 19–25

Measuring committed preadipocytes in human adipose tissue from severely obese patients by using adipocyte fatty acid binding protein

2004 ◽  
Vol 287 (5) ◽  
pp. R1132-R1140 ◽  
Author(s):  
Yourka D. Tchoukalova ◽  
Michael G. Sarr ◽  
Michael D. Jensen
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Droplets ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Human Adipose Tissue ◽  
Cell Number ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Severely Obese

To understand the significance of the reported depot differences in preadipocyte dynamics, we developed a procedure to identify committed preadipocytes in the stromovascular fraction of fresh human adipose tissue. We documented that adipocyte fatty acid binding protein (aP2) is expressed in human preadipocyte clones capable of replication, indicating that can be used as a marker of committed preadipocytes. Because aP2 expression can be induced in macrophages, stromovascular cells were also stained for the macrophage marker CD68. We found aP2+CD68− cells (designated as committed preadipocytes) that did not have lipid droplets (true preadipocytes) and that did have lipid droplets <6.5 μm in diameter (very immature adipocytes). Adipose tissue from subcutaneous, omental, and mesenteric depots was obtained from nine patients undergoing bariatric surgery for measurement of stromovascular cell number, the number of committed preadipocytes (aP2+CD68−), aP2+ macrophages (aP2+CD68+), and aP2− macrophages (aP2−CD68+). The number of committed preadipocytes did not differ significantly between depots but varied >20-fold among individuals. Total cell number, stromovascular cell number, and the number of aP2− macrophages was less ( P < 0.05) in subcutaneous than in omental fat (means ± SE, in millions: subcutaneous, 2.3 ± 0.3, 1.4 ± 0.3, and 0.17 ± 0.08; and omental, 4.8 ± 0.7, 3.8 ± 0.5, and 0.34 ± 0.06); mesenteric depot was intermediate. These data indicate that the cellular composition of adipose tissue varies between depots and between individuals. The ability to quantify committed preadipocytes in fresh adipose tissue should facilitate study of adipose tissue biology.

scholarly journals Molecular and cellular mechanisms of adipogenesis

2015 ◽  
Vol 18 (2) ◽  
pp. 12-19 ◽  
Author(s):  
Alexander Dmitrievich Egorov ◽  
Dmitry Nikolaevich Penkov ◽  
Vsevolod Arsen'evich Tkachuk
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Transcription Factors ◽  
Drug Targets ◽  
Adenosine Monophosphate ◽  
Endocrine Function ◽  
Peroxisome Proliferator ◽  
Cellular Mechanisms ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Impact

The main components of metabolic syndrome include insulin resistance, hypertriglyceridemia and arterial hypertension. Obesity is the cause of metabolic syndrome, mainly as a consequence of the endocrine function of adipose tissue. The volume of adipose tissue depends on the size of individual adipocytes and on their number. The number of adipocytes increases as a result of enhanced adipocyte differentiation. The transcriptional cascade that regulates this differentiation has been well studied. The major adipogenic transcription factor peroxisome proliferator-activated receptor gamma is a ligand-activated nuclear receptor with essential roles in adipogenesis. Its ligands are used to treat metabolic syndrome and type 2 diabetes mellitus. . The present article describes the basic molecular and cellular mechanisms of adipogenesis and discusses the impact of insulin, glucocorticoids, cyclic adenosine monophosphate-activating agents, nuclear receptors and transcription factors on the process of adipogenesis. New regulatory regions of the genome that are capable of binding multiple transcription factors are described, and the most promising drug targets for the treatment of metabolic syndrome and obesity, including the homeodomain proteins Pbx1 and Prep1, are discussed..

In vitro lipid synthesis in human adipose tissue from three abdominal sites

1993 ◽  
Vol 265 (3) ◽  
pp. E374-E379 ◽  
Author(s):  
N. K. Edens ◽  
S. K. Fried ◽  
J. G. Kral ◽  
J. Hirsch ◽  
R. L. Leibel
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Lipid Synthesis ◽  
Human Adipose Tissue ◽  
Obese Women ◽  
Cellular Mechanisms ◽  
Severely Obese ◽  
Fatty Acid Release ◽  
Subcutaneous Adipose

The association between abdominal deposition of adipose tissue and morbidities accompanying obesity may be related to high rates of free fatty acid release from enlarged intra-abdominal stores. To investigate cellular mechanisms that might contribute to enlargement of intra-abdominal adipocytes, lipolysis, triacylglycerol (TG), and diacylglycerol (DG) synthesis from [14C]glucose was measured in abdominal subcutaneous, omental, and mesenteric adipose tissue from severely obese women and men. Subcutaneous adipose tissue from women showed the highest rates of TG synthesis compared with the intra-abdominal site, or any site in men. isoproterenol stimulated TG synthesis more in intra-abdominal than subcutaneous adipose tissue. In the basal state, intra-abdominal adipose tissue from both men and women showed rates of [14C]DG accumulation approximately 50% total [14C]acylglyceride accumulation, whereas, in subcutaneous adipose tissue, [14C]DG accumulation was approximately 25% of total. Basal lipolysis was lower in intra-abdominal than subcutaneous adipocytes. Stimulation of lipolysis reduced [14C]DG accumulation more in intra-abdominal than subcutaneous adipose tissue. Low rates of acylglyceride synthesis in intra-abdominal adipocytes may prevent accumulation of large intra-abdominal fat stores in women.

Regional differences in protein production by human adipose tissue

2001 ◽  
Vol 29 (2) ◽  
pp. 72-75 ◽  
Author(s):  
P. Arner
Keyword(s):  
Adipose Tissue ◽  
Regional Differences ◽  
Protein Production ◽  
Human Adipose Tissue ◽  
Upper Body ◽  
Metabolic Disturbances ◽  
Regional Variations ◽  
Factor Α ◽  
Visceral Adipose ◽  
Activator Inhibitor

Human adipose tissue has an important protein secretory function. Cytokines, hormones, prohormones and enzymes are secreted from fat cells and act in an endocrine or paracrine fashion. The production of several of these proteins is affected by obesity; normally there is an increase in the obese state. Protein production is, as a metabolic activity, subject to regional variations. In particular, the production of leptin, angiotensinogen, interleukin-6 and plasmin activator inhibitor-1 differs between subcutaneous and visceral adipose tissue sites, but no regional differences have been reported in the production of tumour necrosis factor α. It is possible that regional variations in protein production by adipose tissue are of importance in some of the endocrine and metabolic disturbances seen in various forms of obesity, such as visceral and upper-body obesity.

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