scholarly journals Wnt1 Positively Regulates CD36 Expression via TCF4 and PPAR-γ in Macrophages

2015 ◽  
Vol 35 (4) ◽  
pp. 1289-1302 ◽  
Author(s):  
Shuai Wang ◽  
Zewei Sun ◽  
Xi Zhang ◽  
Zhenwei Li ◽  
Mingjie Wu ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Macrophage Differentiation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Cd36 Expression ◽  
Canonical Wnt ◽  
Transcription Factor 4 ◽  
The Relationship

Background: Scavenger receptors including CD36 control the phagocytosis of oxidized low-density lipoprotein and play an important role in macrophage physiology, but the underlying molecular mechanism by which CD36 is regulated in macrophages or during macrophage differentiation from monocytes remains to be determined. Methods: Here, we investigated the relationship between Wnt1 and CD36 during macrophage differentiation. CD36 was suppressed following knockdown of Wnt1 by siRNA, while it was increased by ectopic overexpression of Wnt1 in macrophages. Using a β-catenin inhibitor, peroxisome proliferator-activated receptor gamma (PPAR-γ) siRNA, and transcription factor 4 (TCF4) siRNA, we demonstrated that Wnt1 regulates the expression of CD36 through TCF4 and PPAR-γ. Co-immunoprecipitation, chromatin immunoprecipitation, and immunofluorescence experiments showed that β-catenin interacted with PPAR-γ and that PPAR-γ and TCF4 colocalized in the nucleus. Furthermore, Pax3 regulated Wnt1 via binding to the first binding site in the Wnt1 promoter. Results: Our study demonstrated that during macrophage differentiation from monocytes, Wnt1 promotes CD36 expression via activation of PPAR-γ and TCF4. Conclusions: Our findings suggest that Wnt1 plays an important role in macrophage physiology via activation of the canonical Wnt pathway.

scholarly journals Thioredoxin-Binding Protein-2-Like Inducible Membrane Protein Is a Novel Vitamin D3 and Peroxisome Proliferator-Activated Receptor (PPAR)γ Ligand Target Protein that Regulates PPARγ Signaling

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 733-743 ◽  
Author(s):  
Shin-ichi Oka ◽  
Hiroshi Masutani ◽  
Wenrui Liu ◽  
Hiroyuki Horita ◽  
Dongmei Wang ◽  
...  
Keyword(s):  
Cell Growth ◽  
Membrane Protein ◽  
Vitamin D3 ◽  
Binding Protein ◽  
Low Density Lipoprotein ◽  
Gene Activation ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Thioredoxin binding protein-2 (TBP-2), which is identical with vitamin D3 (VD3) up-regulated protein 1 (VDUP1), plays a crucial role in the integration of glucose and lipid metabolism. There are three highly homologous genes of TBP-2/vitamin D3 up-regulated protein 1 in humans, but their functions remain unclear. Here we characterized a TBP-2 homolog, TBP-2-like inducible membrane protein (TLIMP). In contrast to TBP-2, TLIMP displayed no significant binding affinity for thioredoxin. TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions. VD3 and ligands of peroxisome proliferator-activated receptor (PPAR)-γ, an important regulator of energy metabolism and cell growth inhibition, induced the expression of TLIMP as well as TBP-2. Overexpression of TLIMP suppressed both anchorage-dependent and -independent cell growth and PPARγ ligand-inducible gene activation. These results suggest that TLIMP, a novel VD3- or PPARγ ligand-inducible membrane-associated protein, plays a regulatory role in cell proliferation and PPARγ activation.

Clofibrate causes an upregulation of PPAR-α target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs

2007 ◽  
Vol 293 (1) ◽  
pp. R70-R77 ◽  
Author(s):  
Sebastian Luci ◽  
Beatrice Giemsa ◽  
Holger Kluge ◽  
Klaus Eder
Keyword(s):  
Adipose Tissue ◽  
Target Genes ◽  
Regulatory Element ◽  
Control Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Expression

This study investigated the effect of clofibrate treatment on expression of target genes of peroxisome proliferator-activated receptor (PPAR)-α and various genes of the lipid metabolism in liver and adipose tissue of pigs. An experiment with 18 pigs was performed in which pigs were fed either a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had heavier livers, moderately increased mRNA concentrations of various PPAR-α target genes in liver and adipose tissue, a higher concentration of 3-hydroxybutyrate, and markedly lower concentrations of triglycerides and cholesterol in plasma and lipoproteins than control pigs ( P < 0.05). mRNA concentrations of sterol regulatory element-binding proteins (SREBP)-1 and -2, insulin-induced genes ( Insig) -1 and Insig-2, and the SREBP target genes acetyl-CoA carboxylase, 3-methyl-3-hydroxyglutaryl-CoA reductase, and low-density lipoprotein receptor in liver and adipose tissue and mRNA concentrations of apolipoproteins A-I, A-II, and C-III in the liver were not different between both groups of pigs. In conclusion, this study shows that clofibrate treatment activates PPAR-α in liver and adipose tissue and has a strong hypotriglyceridemic and hypocholesterolemic effect in pigs. The finding that mRNA concentrations of some proteins responsible for the hypolipidemic action of fibrates in humans were not altered suggests that there were certain differences in the mode of action compared with humans. It is also shown that PPAR-α activation by clofibrate does not affect hepatic expression of SREBP target genes involved in synthesis of triglycerides and cholesterol homeostasis in liver and adipose tissue of pigs.

Oxidized low-density lipoprotein and peroxisome-proliferator-activated receptor α down-regulate platelet-activating-factor receptor expression in human macrophages

2001 ◽  
Vol 354 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Delphine HOURTON ◽  
Philippe DELERIVE ◽  
Jana STANKOVA ◽  
Bart STAELS ◽  
M. John CHAPMAN ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Platelet Activating Factor ◽  
Density Lipoprotein ◽  
Receptor Expression ◽  
Peroxisome Proliferator ◽  
Low Density ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Mrna ◽  
Paf Receptor ◽  
Pparα Agonist

Regulation of the expression of platelet-activating factor (PAF) receptor by atherogenic lipoproteins might contribute to atherogenesis. We show that progressive oxidation of low-density lipoprotein (LDL) gradually inhibits PAF receptor expression on the macrophage cell surface. We tested the effect of oxidized LDL (oxLDL) on PAF receptor expression in human monocytes that do not contain peroxisome-proliferator-activated receptor γ (PPARγ), a nuclear receptor activated by oxLDL. OxLDL decreased by 50% (P ⩽0.001) and by 29% (P⩽0.05) the binding of PAF and the expression of PAF receptor mRNA respectively. Next we demonstrated that progressive oxidation of LDLs significantly activated PPARα-dependent transcription in transfected mouse aortic endothelial cells. Finally we demonstrated, in mature macrophages, that fenofibrate (20µM), a specific PPARα agonist, but not the specific PPARγ agonist BRL49653 (20nM), significantly decreased both PAF binding and PAF receptor mRNA expression, by 65% and 40% (P⩽0.001) respectively. Additionally, another PPARα agonist, Wy14,643, decreased PAF receptor promoter activity by 70% (P⩽0.05) in transfected THP-1 cells, suggesting the involvement of the proximal promoter region (-980 to -500) containing a series of four nuclear factor (NF)-κB motifs. Thus PPARα might be involved in the down-regulation of PAF receptor gene expression by oxLDLs in human monocytes/macrophages. The oxidation of one or more lipid components of LDLs might result in the formation of natural activators of PPARα. It is hypothesized that such activators might modulate inflammation and apoptosis upon atherogenesis by decreasing the expression of PAF receptor.

scholarly journals The Importance of Fatty Acids as Nutrients during Post-Exercise Recovery

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 280 ◽  
Author(s):  
Anne-Marie Lundsgaard ◽  
Andreas M. Fritzen ◽  
Bente Kiens
Keyword(s):  
Skeletal Muscle ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Whole Body ◽  
Tissue Blood Flow ◽  
Peroxisome Proliferator ◽  
Early Recovery ◽  
Peroxisome Proliferator Activated Receptor ◽  
Post Exercise ◽  
Exercise Induced

It is well recognized that whole-body fatty acid (FA) oxidation remains increased for several hours following aerobic endurance exercise, even despite carbohydrate intake. However, the mechanisms involved herein have hitherto not been subject to a thorough evaluation. In immediate and early recovery (0–4 h), plasma FA availability is high, which seems mainly to be a result of hormonal factors and increased adipose tissue blood flow. The increased circulating availability of adipose-derived FA, coupled with FA from lipoprotein lipase (LPL)-derived very-low density lipoprotein (VLDL)-triacylglycerol (TG) hydrolysis in skeletal muscle capillaries and hydrolysis of TG within the muscle together act as substrates for the increased mitochondrial FA oxidation post-exercise. Within the skeletal muscle cells, increased reliance on FA oxidation likely results from enhanced FA uptake into the mitochondria through the carnitine palmitoyltransferase (CPT) 1 reaction, and concomitant AMP-activated protein kinase (AMPK)-mediated pyruvate dehydrogenase (PDH) inhibition of glucose oxidation. Together this allows glucose taken up by the skeletal muscles to be directed towards the resynthesis of glycogen. Besides being oxidized, FAs also seem to be crucial signaling molecules for peroxisome proliferator-activated receptor (PPAR) signaling post-exercise, and thus for induction of the exercise-induced FA oxidative gene adaptation program in skeletal muscle following exercise. Collectively, a high FA turnover in recovery seems essential to regain whole-body substrate homeostasis.

scholarly journals Carbamazepine Enhances Adipogenesis by Inhibiting Wnt/β-catenin Expression

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1460 ◽  
Author(s):  
Im ◽  
Kim ◽  
Chau ◽  
Um
Keyword(s):  
Fatty Acid Synthase ◽  
Glycogen Synthase ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Negative Regulator ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Levels ◽  
Density Lipoprotein Receptor ◽  
Prevalence Of Obesity

Carbamazepine is a drug that is widely used in the treatment of epilepsy and bipolar disorder. The prevalence of obesity in patients treated with carbamazepine has been frequently reported. However, whether carbamazepine affects adipogenesis, one of the critical steps in the development of obesity, remains unclear. Here, we show that carbamazepine increased the expression levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein β (C/EBPβ), and fatty acid synthase (FASN) in 3T3-L1 cells. Notably, carbamazepine inhibited the expression levels of β-catenin, a negative regulator of adipogenesis, leading to enhanced adipogenesis. Conversely, β-catenin overexpression abolished the effect of carbamazepine on adipogenic gene expression. However, depletion of β-catenin further enhanced PPARγ expression. In addition, carbamazepine reduced β-catenin expression by lowering the levels of phospho-low density lipoprotein receptor-related protein 6 (p-LRP6) and phospho-glycogen synthase kinase 3β (p-GSK3β) in Wnt/β-catenin signaling. Moreover, carbamazepine reduced Wnt mRNA expression and decreased the promoter activities of TCF, the target of β-catenin during adipogenesis. These results suggest that carbamazepine enhances adipogenesis by suppressing Wnt/β-catenin expression, indicating its potential effects on obesity-related metabolism.

scholarly journals Beta-sitosterol upregulated paraoxonase-1 via peroxisome proliferator-activated receptor-γ in irradiated rats

2017 ◽  
Vol 95 (6) ◽  
pp. 661-666 ◽  
Author(s):  
Enas Mahmoud Moustafa ◽  
Noura Magdy Thabet
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Enzyme Activities ◽  
Liver Tissue ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Oxidative Stress Marker ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

This study was designed to evaluate the effect of beta-sitosterol (BS) on the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression role in the activity of paraoxonase (PON-1) enzyme in oxidative stress status of irradiated rats. Animals were exposed to whole body γ-radiation single dose 6 Gy and received BS dose (40 mg·(kg body mass)−1·day−1, orally). In liver tissue, gene expression of PPAR-γ ligand was determined. Oxidative stress marker (malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), PON-1, and arylesterase (ARE)) were assayed in serum and liver tissue. Also, serum lipid profile (cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) was measured. In irradiated animals that received BS, expression of PPAR-γ ligand increase significantly associated with increase in PON-1 and ARE enzyme activities. Also, the activities of SOD, CAT enzymes, and HDL-c levels display elevation. By contrast, significant decrease in MDA content, cholesterol, TG, and LDL-c levels were revealed after BS administration. Our findings in this study provide the evidence that BS has radio-protective effect via regulating the gene expression of PPAR-γ, causing an increase in PON-1 and ARE enzyme activities. This action of BS is due to its free radical scavenging properties, antioxidant effect, lowering of cholesterol, and PPAR-γ agonist properties.

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