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.

scholarly journals PKA regulatory subunit R2B is required for murine and human adipocyte differentiation

2013 ◽  
Vol 2 (4) ◽  
pp. 196-207 ◽  
Author(s):  
Erika Peverelli ◽  
Federica Ermetici ◽  
Sabrina Corbetta ◽  
Ettore Gozzini ◽  
Laura Avagliano ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fetal Development ◽  
Adipocyte Differentiation ◽  
Human Adipose Tissue ◽  
Regulatory Subunit ◽  
Regulatory Subunits ◽  
Triglyceride Accumulation ◽  
Human Preadipocytes ◽  
Pka Regulatory Subunit ◽  
Intracellular Triglyceride

Adipogenesis is a complex process modulated by several factors, including cAMP signaling. The main cAMP target is protein kinase A (PKA), a tetrameric enzyme with four regulatory subunits showing tissue-specific expression and function: PRKAR2B is the main regulatory subunit in adipose tissue in mice and in adult humans. This study aimed to evaluate the expression of PKA regulatory subunits in human adipose tissue during fetal development and to investigate their role in the differentiation of 3T3-L1 and primary human preadipocytes. The expression of PKA regulatory subunits was evaluated in fetal adipose tissue (immunohistochemistry) and in cultured 3T3-L1 and primary human preadipocytes (western blot analysis). Cultured cells were transiently transfected with siRNA against PRKAR2B and induced to differentiate. Differentiation was evaluated by intracellular triglyceride staining (Oil Red O) and expression of molecular markers of adipocyte differentiation. In this study, we found that PRKAR2B is the main regulatory subunit in human adipose tissue during fetal development, from 12 weeks of gestation to the end of gestation, as well as in 3T3-L1 and primary human preadipocytes. The expression of PRKAR2B increases progressively during in vitro differentiation. The silencing of PRKAR2B abolishes the increase in the expression of peroxisome proliferator-activated receptor gamma (PPARγ (PPARG)), fatty acid synthase, aP2 (FABP4), and lipoprotein lipase, as well as intracellular triglyceride accumulation, resulting in impaired adipocyte differentiation in both mouse and human cell systems. In conclusion, PRKAR2B is the key PKA regulatory subunit involved in mouse and human adipose tissue development. The physiological increase in the expression of PRKAR2B is an essential event in adipogenesis in both mice and humans, and it might represent a possible target for future strategies for obesity treatment.

Adipocyte differentiation of multipotent cells established from human adipose tissue

2004 ◽  
Vol 315 (2) ◽  
pp. 255-263 ◽  
Author(s):  
Anne-Marie Rodriguez ◽  
Christian Elabd ◽  
Frédéric Delteil ◽  
Julien Astier ◽  
Cécile Vernochet ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Human Adipose Tissue ◽  
Multipotent Cells

scholarly journals Hypoxia Alters the Expression of Dipeptidyl Peptidase 4 and Induces Developmental Remodeling of Human Preadipocytes

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Helena H. Chowdhury ◽  
Jelena Velebit ◽  
Nataša Radić ◽  
Vito Frančič ◽  
Marko Kreft ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Transmembrane Protein ◽  
Human Adipose Tissue ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Hypoxic Conditions ◽  
Human Preadipocytes ◽  
Developmental Remodeling

Dipeptidyl peptidase 4 (DPP4), a transmembrane protein, has been identified in human adipose tissue and is considered to be associated with obesity-related type 2 diabetes. Since adipose tissue is relatively hypoxic in obese participants, we investigated the expression of DPP4 in human preadipocytes (hPA) and adipocytes in hypoxia, during differentiation and upon insulin stimulation. The results show that DPP4 is abundantly expressed in hPA but very sparsely in adipocytes. During differentiationin vitro, the expression of DPP4 in hPA is reduced on the addition of differentiation medium, indicating that this protein can be hPA marker. Long term hypoxia altered the expression of DPP4 in hPA. Inin vitrohypoxic conditions the protease activity of shed DPP4 is reduced; however, in the presence of insulin, the increase in DPP4 expression is potentiated by hypoxia.

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 CD90 Is Dispensable for White and Beige/Brown Adipocyte Differentiation

2020 ◽  
Vol 21 (21) ◽  
pp. 7907
Author(s):  
Meike Dahlhaus ◽  
Julian Roos ◽  
Daniel Engel ◽  
Daniel Tews ◽  
Daniel Halbgebauer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Stromal Cells ◽  
Adipocyte Differentiation ◽  
Human Adipose Tissue ◽  
Brown Adipocyte ◽  
White Adipocyte ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Adipose Tissue Stromal Cells ◽  
Flow Cytometric Sorting

Brown adipose tissue (BAT) is a thermogenic organ in rodents and humans. In mice, the transplantation of BAT has been successfully used to combat obesity and its comorbidities. While such beneficial properties of BAT are now evident, the developmental and cellular origins of brown, beige, and white adipocytes have remained only poorly understood, especially in humans. We recently discovered that CD90 is highly expressed in stromal cells isolated from human white adipose tissue (WAT) compared to BAT. Here, we studied whether CD90 interferes with brown or white adipogenesis or white adipocyte beiging. We applied flow cytometric sorting of human adipose tissue stromal cells (ASCs), a CRISPR/Cas9 knockout strategy in the human Simpson-Golabi-Behmel syndrome (SGBS) adipocyte model system, as well as a siRNA approach in human approaches supports the hypothesis that CD90 affects brown or white adipogenesis or white adipocyte beiging in humans. Taken together, our findings call the conclusions drawn from previous studies, which claimed a central role of CD90 in adipocyte differentiation, into question.

scholarly journals Adipocyte differentiation impairment as well as lipid metabolism and transport problems – major causes of genetic lipodystrophies

2019 ◽  
Vol 73 ◽  
pp. 741-761
Author(s):  
Agnieszka Dettlaff-Pokora
Keyword(s):  
Adipose Tissue ◽  
Primary Care Physicians ◽  
Adipocyte Differentiation ◽  
Plasma Cholesterol ◽  
Correct Diagnosis ◽  
Hdl Cholesterol ◽  
Diagnostic Methods ◽  
Tissue Loss ◽  
Ectopic Fat ◽  
Fat Accumulation

Lipodystrophies are heterogenic group of adipose tissue disorders with its general or partial atrophy. In case of congenital lipodystrophies disturbances of adipogenesis or/and alterations of adipocyte differentiation often occur leading to thermogenic adipocytes formation. Basic adipocyte functions can be perturbed, including improper synthesis of triacylglycerols and phospholipids of lipid droplet, but also impaired fatty acids release and intracellular lipid traffic. Lipodystrophy can result from weakening of adipose tissue structure, but also from improper function of both cytoskeleton and nuclear lamina leading to cell dysfunction. Lack of adipose tissue leads to a) increased plasma triacylglycerols level and ectopic fat accumulation in other tissues; b) total plasma cholesterol increase; c) plasma HDL-cholesterol decrease. Ectopic fat accumulation in liver can cause fatty liver and with time can lead to hepatomegaly and liver cirrhosis. Dysfunctions are proportional to the extent of fat tissue loss with generalized lipodystrophies patients developing complications at early ages. Diabetes and insulin resistance are common comorbidities. Improvement of diagnostic methods of medical genetics allows precise determination of their genotypes and correct diagnosis of patients suffering from lipodystrophy. For that reason number of described cases increased in recent years, also in Poland. New lipodystrophy types were described. Therefore there is a need to bring lipodystrophy syndromes for the attention of primary care physicians, pediatricians and endocrinologists.

Direct attenuation of plasminogen activator inhibitor type-1 expression in human adipose tissue by thiazolidinediones

2004 ◽  
Vol 91 (04) ◽  
pp. 674-682 ◽  
Author(s):  
Anne Leugers ◽  
Jens Lohrmann ◽  
Sandra Ernst ◽  
Burton Sobel ◽  
Christoph Bode ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cardiovascular Risk ◽  
Plasminogen Activator Inhibitor ◽  
Human Adipose Tissue ◽  
Ppar Γ ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Pai 1

SummaryAdipose tissue produces substantial amounts of plasminogen activator inhibitor type-1 (PAI-1), an established cardiovascular risk factor. This study evaluated PAI-1 expression in human adipose tissue in response to thiazolidinediones, insulin sensitising drugs activating peroxisome proliferator-activated receptorgamma (PPAR-γ). Troglitazone, rosiglitazone, and ciglitazone significantly reduced PAI-1 protein expression in human preadipocytes under basal conditions and after stimulation of the cells with TGF-β. Pioglitazone had no effect. In human adipocytes all four thiazolidinediones significantly attenuated PAI-1 expression. Signalling appeared to be mediated via PPAR-γ and effects reflected, at least in part, changes in transcription. Accordingly, patients with insulin resistance may benefit from treatment with thiazolidinediones with respect to diminution of PAI-1 expression in adipose tissue and consequent potential reduction of cardiovascular risk.

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