scholarly journals Genome-Wide Profiling of Peroxisome Proliferator-Activated Receptor   in Primary Epididymal, Inguinal, and Brown Adipocytes Reveals Depot-Selective Binding Correlated with Gene Expression

2012 ◽  
Vol 32 (17) ◽  
pp. 3452-3463 ◽  
Author(s):  
M. S. Siersbaek ◽  
A. Loft ◽  
M. M. Aagaard ◽  
R. Nielsen ◽  
S. F. Schmidt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peroxisome Proliferator ◽  
Brown Adipocytes ◽  
Selective Binding ◽  
Peroxisome Proliferator Activated Receptor ◽  
Genome Wide

scholarly journals Defective thermoregulation, impaired lipid metabolism, but preserved adrenergic induction of gene expression in brown fat of mice lacking C/EBPβ

2005 ◽  
Vol 389 (1) ◽  
pp. 47-56 ◽  
Author(s):  
M. Carmen CARMONA ◽  
Elayne HONDARES ◽  
M. Luisa RODRÍGUEZ DE LA CONCEPCIÓN ◽  
Víctor RODRÍGUEZ-SUREDA ◽  
Julia PEINADO-ONSURBE ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uncoupling Protein ◽  
Marker Gene ◽  
Gene Promoter ◽  
Brown Fat ◽  
Specific Marker ◽  
Peroxisome Proliferator ◽  
Inhibitory Protein ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor

C/EBPβ (CCAAT/enhancer-binding protein β) is a transcriptional regulator of the UCP1 (uncoupling protein-1) gene, the specific marker gene of brown adipocytes that is responsible for their thermogenic capacity. To investigate the role of C/EBPβ in brown fat, we studied the C/EBPβ-null mice. When placed in the cold, C/EBPβ−/− mice did not maintain body temperature. This cold-sensitive phenotype occurred, although UCP1 and PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) gene expression was unaltered in brown fat of C/EBPβ−/− mice. The UCP1 gene promoter was repressed by the truncated inhibitory C/EBPβ isoform LIP (liver-enriched transcriptional inhibitory protein, the truncated inhibitory C/EBPβ isoform). Since C/EBPβ-null mice lack both C/EBPβ isoforms, active LAP (liver-enriched transcriptional activatory protein, the active C/EBPβ isoform) and LIP, the absence of LIP may have a stronger effect than the absence of LAP upon UCP1 gene expression. Gene expression for UCP2 and UCP3 was not impaired in all tissues analysed. In primary brown adipocytes from C/EBPβ−/− mice, induction of gene expression by noradrenaline was preserved. In contrast, the expression of genes related to lipid storage was impaired, as was the amount of triacylglycerol mobilized after acute cold exposure in brown fat from C/EBPβ−/− mice. LPL (lipoprotein lipase) activity was also impaired in brown fat, but not in other tissues of C/EBPβ−/− mice. LPL protein levels were also diminished, but this effect was independent of changes in LPL mRNA, suggesting that C/EBPβ is involved in the post-transcriptional regulation of LPL gene expression in brown fat. In summary, defective thermoregulation owing to the lack of C/EBPβ is associated with the reduced capacity to supply fatty acids as fuels to sustain brown fat thermogenesis.

scholarly journals Noradrenaline represses PPAR (peroxisome-proliferator-activated receptor) γ2 gene expression in brown adipocytes: intracellular signalling and effects on PPARγ2 and PPARγ1 protein levels

2004 ◽  
Vol 382 (2) ◽  
pp. 597-606 ◽  
Author(s):  
Eva M. LINDGREN ◽  
Ronni NIELSEN ◽  
Natasa PETROVIC ◽  
Anders JACOBSSON ◽  
Susanne MANDRUP ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Down Regulation ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Pparγ Gene ◽  
Kinase A

PPAR (peroxisome-proliferator-activated receptor) γ is expressed in brown and white adipose tissues and is involved in the control of differentiation and proliferation. Noradrenaline stimulates brown pre-adipocyte proliferation and brown adipocyte differentiation. The aim of the present study was thus to investigate the influence of noradrenaline on PPARγ gene expression in brown adipocytes. In primary cultures of brown adipocytes, PPARγ2 mRNA levels were 20-fold higher than PPARγ1 mRNA levels. PPARγ expression occurred during both the proliferation and the differentiation phases, with the highest mRNA levels being found at the time of transition between the phases. PPARγ2 mRNA levels were downregulated by noradrenaline treatment (EC50, 0.1 μM) in both proliferative and differentiating cells, with a lagtime of 1 h and lasting up to 4 h, after which expression gradually recovered. The down-regulation was β-adrenoceptor-induced and intracellularly mediated via cAMP and protein kinase A; the signalling pathway did not involve phosphoinositide 3-kinase, Src, p38 mitogen-activated protein kinase or extracellular-signal-regulated kinases 1 and 2. Treatment of the cells with the protein synthesis inhibitor cycloheximide not only abolished the noradrenaline-induced down-regulation of PPARγ2 mRNA, but also in itself induced PPARγ2 hyperexpression. The down-regulation was probably the result of suppression of transcription. The down-regulation of PPARγ2 mRNA resulted in similar down-regulation of PPARγ2 and phosphoPPARγ2 protein levels. Remarkably, the level of PPARγ1 protein was similar to that of PPARγ2 (despite almost no PPARγ1 mRNA), and the down-regulation by noradrenaline demonstrated similar kinetics to that of PPARγ2; thus PPARγ1 was apparently translated from the PPARγ2 template. It is suggested that β-adrenergic stimulation via cAMP and protein kinase A represses PPARγ gene expression, leading to reduction of PPARγ2 mRNA levels, which is then reflected in down-regulated levels of PPARγ2, phosphoPPARγ2 and PPARγ1.

scholarly journals Effect of Salusin-ß on Peroxisome Proliferator-Activated Receptor Gamma Gene Expression in Vascular Smooth Muscle Cells and its Possible Mechanism

2015 ◽  
Vol 36 (6) ◽  
pp. 2466-2479 ◽  
Author(s):  
XiaoLe Xu ◽  
Mengzi He ◽  
Tingting Liu ◽  
Yi Zeng ◽  
Wei Zhang
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Nuclear Translocation ◽  
Muscle Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Gene

Background/Aims: salusin-ß is considered to be a potential pro-atherosclerotic factor. Regulation and function of vascular smooth muscle cells (VSMCs) are important in the progression of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ) exerts a vascular protective role beyond its metabolic effects. Salusin-ß has direct effects on VSMCs. The aim of the present study was to assess the effect of salusin-ß on PPARγ gene expression in primary cultured rat VSMCs. Methods: Western blotting analysis, real-time PCR and transient transfection approach were used to determine expression of target proteins. Specific protein knockdown was performed with siRNA transfection. Cell proliferation was determined by 5-bromo-2'-deoxyuridine incorporation. The levels of inflammation indicators interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) were determined using enzyme-linked immunosorbent assay. Results: Salusin-ß negatively regulated PPARγ gene expression at protein, mRNA and gene promoter level in VSMCs. The inhibitory effect of salusin-ß on PPARγ gene expression contributed to salusin-ß-induced VSMCs proliferation and inflammation in vitro. IγBa-NF-γB activation, but not NF-γB p50 or p65, mediated the salusin-ß-induced inhibition of PPARγ gene expression. Salusin-ß induced nuclear translocation of histone deacetylase 3 (HDAC3). HDAC3 siRNA prevented salusin-ß-induced PPARγ reduction. Nuclear translocation of HDAC3 in response to salusin-ß was significantly reversed by an IγBa inhibitor BAY 11-7085. Furthermore, IγBa-HDAC3 complex was present in the cytosol of VSMCs but interrupted after salusin-ß treatment. Conclusion: IγBa-HDAC3 pathway may contribute to salusin-ß-induced inhibition of PPARγ gene expression in VSMCs.

scholarly journals Opposing Roles of Peroxisome Proliferator-activated Receptor α and Growth Hormone in the Regulation of CYP4A11 Expression in a Transgenic Mouse Model

2009 ◽  
Vol 284 (24) ◽  
pp. 16541-16552 ◽  
Author(s):  
Üzen Savas ◽  
Daniel E. W. Machemer ◽  
Mei-Hui Hsu ◽  
Pryce Gaynor ◽  
Jerome M. Lasker ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone ◽  
Transgenic Mice ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Peroxisome Proliferator ◽  
Sexually Dimorphic ◽  
Peroxisome Proliferator Activated Receptor ◽  
Liver And Kidney

CYP4A11 transgenic mice (CYP4A11 Tg) were generated to examine in vivo regulation of the human CYP4A11 gene. Expression of CYP4A11 in mice yields liver and kidney P450 4A11 levels similar to those found in the corresponding human tissues and leads to an increased microsomal capacity for ω-hydroxylation of lauric acid. Fasted CYP4A11 Tg mice exhibit 2–3-fold increases in hepatic CYP4A11 mRNA and protein, and this response is absent in peroxisome proliferator-activated receptor α (PPARα) null mice. Dietary administration of either of the PPARα agonists, fenofibrate or clofibric acid, increases hepatic and renal CYP4A11 levels by 2–3-fold, and these responses were also abrogated in PPARα null mice. Basal liver CYP4A11 levels are reduced differentially in PPARα−/− females (>95%) and males (<50%) compared with PPARα−/+ mice. Quantitative and temporal differences in growth hormone secretion are known to alter hepatic lipid metabolism and to underlie sexually dimorphic gene expression, respectively. Continuous infusion of low levels of growth hormone reduced CYP4A11 expression by 50% in PPARα-proficient male and female transgenic mice. A larger decrease was observed for the expression of CYP4A11 in PPARα−/− CYP4A11 Tg male mice to levels similar to that of female PPARα-deficient mice. These results suggest that PPARα contributes to the maintenance of basal CYP4A11 expression and mediates CYP4A11 induction in response to fibrates or fasting. In contrast, increased exposure to growth hormone down-regulates CYP4A11 expression in liver.

Abstract 290: Proliferation of Cardiac Fibroblasts Defines Early Stages of Genetic Dilated Cardiomyopathy and Precedes Myocardial Metabolic Derangement

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Michael A Burke ◽  
Stephen Chang ◽  
Danos C Christodoulou ◽  
Joshua M Gorham ◽  
Hiroko Wakimoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Fibroblasts ◽  
Expression Patterns ◽  
Molecular Networks ◽  
Peroxisome Proliferator ◽  
Metabolic Derangement ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Remodeling ◽  
Ppar Signaling ◽  
Myocyte Proliferation

The complex molecular networks underpinning DCM remain poorly understood. To study distinct pathways and networks in the longitudinal development of DCM we performed RNAseq on LV tissue from mice carrying a human DCM mutation in phospholamban (PLN R9C/+ ) before phenotype onset (pre-DCM), with DCM, and during overt heart failure (HF), and also on isolated myocytes and non-myocytes from DCM hearts. PLN R9C/+ mice show progressive fibrosis (20% vs. 1% control, p=6x10 −33 ; n=3) associated with proliferation of cardiac non-myocytes (33% increase over control, p=6x10 −4 ; n=3). Consistent with this, cardiac non-myocytes have upregulated gene expression and pathways, while these are generally downregulated in myocytes. Non-myocytes were enriched in fibrosis, inflammation, and cell remodeling pathways, from pre-DCM to HF. In contrast, myocytes were enriched for metabolic pathways only with overt DCM and HF. Myocytes showed profound derangement of oxidative phosphorylation with DCM (p=2.5x10 −41 ; 44% (53/120) of pathway genes downregulated), suggesting mitochondrial dysfunction. Additionally, we detected probable inhibition of peroxisome proliferator-activated receptor (PPAR) signaling by diminished expression of pathway genes (Figure). DCM and hypertrophic remodeling was compared using RNAseq of a mouse model of HCM; similar patterns of fibrosis with myocyte metabolic dysregulation were evident despite unique differential gene expression patterns between models. DCM caused by PLN R9C/+ is associated with early non-myocyte proliferation and later myocyte metabolic derangement possibly governed by altered PPAR signaling, and is common to DCM and HCM.

Enrichment of IGF-1R and PPARγ signalling pathways in orbital inflammatory diseases: steps toward understanding pathogenesis

2021 ◽  
pp. bjophthalmol-2020-318330
Author(s):  
Rohan Verma ◽  
Dongseok Choi ◽  
Allison J Chen ◽  
Christina A Harrington ◽  
David J Wilson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Diseases ◽  
Target Therapy ◽  
Signalling Pathways ◽  
Peroxisome Proliferator ◽  
Healthy Controls ◽  
Gene Expressions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Orbital Inflammation ◽  
Wide Range

BackgroundOrbital inflammatory disease (OID) encompasses a wide range of pathology including thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis and non-specific orbital inflammation (NSOI), accounting for up to 6% of orbital diseases. Understanding the underlying pathophysiology of OID can improve diagnosis and help target therapy.AimsTo test the hypothesis that shared signalling pathways are activated in different forms of OID.MethodsIn this secondary analysis, pathway analysis was performed on the previously reported differentially expressed genes from orbital adipose tissue using patients with OID and healthy controls who were characterised by microarray. For the original publications, tissue specimens were collected from oculoplastic surgeons at 10 international centres representing four countries (USA, Canada, Australia and Saudi Arabia). Diagnoses were independently confirmed by two masked ocular pathologists (DJW, HEG). Gene expression profiling analysis was performed at the Oregon Health & Science University. Eighty-three participants were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 25 with NSOI and 20 healthy controls.ResultsAmong the 83 subjects (mean (SD) age, 52.8 (18.3) years; 70% (n=58) female), those with OID demonstrated perturbation of the downstream gene expressions of the IGF-1R (MAPK/RAS/RAF/MEK/ERK and PI3K/Akt/mTOR pathways), peroxisome proliferator-activated receptor-γ (PPARγ), adipocytokine and AMPK signalling pathways compared with healthy controls. Specifically, GPA samples differed from controls in gene expression within the insulin-like growth factor-1 receptor (IGF-1R, PI3K-Akt (p=0.001), RAS (p=0.005)), PPARγ (p=0.002), adipocytokine (p=0.004) or AMPK (p=<0.001) pathways. TAO, sarcoidosis and NSOI samples were also found to have statistically significant differential gene expression in these pathways.ConclusionsAlthough OID includes a heterogenous group of pathologies, TAO, GPA, sarcoidosis and NSOI share enrichment of common gene signalling pathways, namely IGF-1R, PPARγ, adipocytokine and AMPK. Pathway analyses of gene expression suggest that other forms of orbital inflammation in addition to TAO may benefit from blockade of IGF-1R signalling pathways.

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