scholarly journals Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARα in murine heart

2005 ◽  
Vol 385 (2) ◽  
pp. 469-477 ◽  
Author(s):  
Biao LU ◽  
Yan J. JIANG ◽  
Yaling ZHOU ◽  
Fred Y. XU ◽  
Grant M. HATCH ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Tissue Expression ◽  
In Vitro Transcription ◽  
Amino Acid Sequences ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor

AGPAT (1-acyl-sn-glycerol 3-phosphate acyltransferase) exists in at least five isoforms in humans, termed as AGPAT1, AGPAT2, AGPAT3, AGPAT4 and AGPAT5. Although they catalyse the same biochemical reaction, their relative function, tissue expression and regulation are poorly understood. Linkage studies in humans have revealed that AGPAT2 contributes to glycerolipid synthesis and plays an important role in regulating lipid metabolism. We report the molecular cloning, tissue distribution, and enzyme characterization of mAGPATs (murine AGPATs) and regulation of cardiac mAGPATs by PPARα (peroxisome-proliferator-activated receptor α). mAGPATs demonstrated differential tissue expression profiles: mAGPAT1 and mAGPAT3 were ubiquitously expressed in most tissues, whereas mAGPAT2, mAGPAT4 and mAGPAT5 were expressed in a tissue-specific manner. mAGPAT2 expressed in in vitro transcription and translation reactions and in transfected COS-1 cells exhibited specificity for 1-acyl-sn-glycerol 3-phosphate. When amino acid sequences of five mAGPATs were compared, three highly conserved motifs were identified, including one novel motif/pattern KX2LX6GX12R. Cardiac mAGPAT activities were 25% lower (P<0.05) in PPARα null mice compared with wild-type. In addition, cardiac mAGPAT activities were 50% lower (P<0.05) in PPARα null mice fed clofibrate compared with clofibrate fed wild-type animals. This modulation of AGPAT activity was accompanied by significant enhancement/reduction of the mRNA levels of mAGPAT3/mAGPAT2 respectively. Finally, mRNA expression of cardiac mAGPAT3 appeared to be regulated by PPARα activation. We conclude that cardiac mAGPAT activity may be regulated by both the composition of mAGPAT isoforms and the levels of each isoform.

scholarly journals Enhanced Therapeutic Potential of the Secretome Released from Adipose-Derived Stem Cells by PGC-1α-Driven Upregulation of Mitochondrial Proliferation

2019 ◽  
Vol 20 (22) ◽  
pp. 5589
Author(s):  
Jaeim Lee ◽  
Ok-Hee Kim ◽  
Sang Chul Lee ◽  
Kee-Hwan Kim ◽  
Jin Sun Shin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Injury ◽  
Therapeutic Potential ◽  
Tissue Expression ◽  
In Vitro Models ◽  
Peroxisome Proliferator ◽  
Adipose Derived Stem Cells ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome proliferator activated receptor λ coactivator 1α (PGC-1α) is a potent regulator of mitochondrial biogenesis and energy metabolism. In this study, we investigated the therapeutic potential of the secretome released from the adipose-derived stem cells (ASCs) transfected with PGC-1α (PGC-secretome). We first generated PGC-1α-overexpressing ASCs by transfecting ASCs with the plasmids harboring the gene encoding PGC-1α. Secretory materials released from PGC-1α-overexpressing ASCs were collected and their therapeutic potential was determined using in vitro (thioacetamide (TAA)-treated AML12 cells) and in vivo (70% partial hepatectomized mice) models of liver injury. In the TAA-treated AML12 cells, the PGC-secretome significantly increased cell viability, promoted expression of proliferation-related markers, such as PCNA and p-STAT, and significantly reduced the levels of reactive oxygen species (ROS). In the mice, PGC-secretome injections significantly increased liver tissue expression of proliferation-related markers more than normal secretome injections did (p < 0.05). We demonstrated that the PGC-secretome does not only have higher antioxidant and anti-inflammatory properties, but also has the potential of significantly enhancing liver regeneration in both in vivo and in vitro models of liver injury. Thus, reinforcing the mitochondrial antioxidant potential by transfecting ASCs with PGC-1α could be one of the effective strategies to enhance the therapeutic potential of ASCs.

scholarly journals Angiogenic Deficiency and Adipose Tissue Dysfunction Are Associated with Macrophage Malfunction in SIRT1−/− Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1706-1716 ◽  
Author(s):  
Fen Xu ◽  
David Burk ◽  
Zhanguo Gao ◽  
Jun Yin ◽  
Xia Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Nuclear Factor Κb ◽  
The Body ◽  
Sirtuin 1 ◽  
Vascular Density ◽  
Peroxisome Proliferator ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1−/−) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1−/− mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1−/− mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1−/− mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue.

scholarly journals Expression of peroxisome proliferator-activated receptor-γ in macrophage suppresses experimentally induced colitis

2007 ◽  
Vol 292 (2) ◽  
pp. G657-G666 ◽  
Author(s):  
Yatrik M. Shah ◽  
Keiichirou Morimura ◽  
Frank J. Gonzalez
Keyword(s):  
Clinical Symptoms ◽  
Body Weight Loss ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Wild Type ◽  
Targeted Disruption ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Cytokine Analysis ◽  
Increased Susceptibility

Peroxisome proliferator-activated receptor-γ (PPAR-γ) has been shown to be a protective transcription factor in mouse models of inflammatory bowel disease (IBD). PPAR-γ is expressed in several different cell types, and mice with a targeted disruption of the PPAR-γ gene in intestinal epithelial cells demonstrated increased susceptibility to dextran sulfate sodium (DSS)-induced IBD. However, the highly selective PPAR-γ ligand rosiglitazone decreased the severity of DSS-induced colitis and suppressed cytokine production in both PPAR-γ intestinal specific null mice and wild-type littermates. Therefore the role of PPAR-γ in different tissues and their contribution to the pathogenesis of IBD still remain unclear. Mice with a targeted disruption of PPAR-γ in macrophages (PPAR-γΔMφ) and wild-type littermates (PPAR-γF/F) were administered 2.5% DSS in drinking water to induce IBD. Typical clinical symptoms were evaluated on a daily basis, and proinflammatory cytokine analysis was performed. PPAR-γΔMφ mice displayed an increased susceptibility to DSS-induced colitis compared with wild-type littermates, as defined by body weight loss, diarrhea, rectal bleeding score, colon length, and histology. IL-1β, CCR2, MCP-1, and inducible nitric oxide synthase mRNA levels in colons of PPAR-γΔMφ mice treated with DSS were higher than in similarly treated PPAR-γF/F mice. The present study has identified a novel protective role for macrophage PPAR-γ in the DSS-induced IBD model. The data suggest that PPAR-γ regulates recruitment of macrophages to inflammatory foci in the colon.

scholarly journals PRIC295, a Nuclear Receptor Coactivator, Identified from PPAR-Interacting Cofactor Complex

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-16 ◽  
Author(s):  
Sean R. Pyper ◽  
Navin Viswakarma ◽  
Yuzhi Jia ◽  
Yi-Jun Zhu ◽  
Joseph D. Fondell ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Target Genes ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nuclear Receptor Coactivator ◽  
Evolutionarily Conserved

The peroxisome proliferator-activated receptor- (PPAR) plays a key role in lipid metabolism and energy combustion. Chronic activation of PPAR in rodents leads to the development of hepatocellular carcinomas. The ability of PPAR to induce expression of its target genes depends on Mediator, an evolutionarily conserved complex of cofactors and, in particular, the subunit 1 (Med1) of this complex. Here, we report the identification and characterization of PPAR-interacting cofactor (PRIC)-295 (PRIC295), a novel coactivator protein, and show that it interacts with the Med1 and Med24 subunits of the Mediator complex. PRIC295 contains 10 LXXLL signature motifs that facilitate nuclear receptor binding and interacts with PPAR and five other members of the nuclear receptor superfamily in a ligand-dependent manner. PRIC295 enhances the transactivation function of PPAR, PPAR, and ER. These data demonstrate that PRIC295 interacts with nuclear receptors such as PPAR and functions as a transcription coactivator underin vitroconditions and may play an important role in mediating the effectsin vivoas a member of the PRIC complex with Med1 and Med24.

scholarly journals Key wheat GRF genes constraining wheat tillering of mutant dmc

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11235
Author(s):  
Jing Zhang ◽  
Junchang Li ◽  
Yongjing Ni ◽  
Yumei Jiang ◽  
Zhixin Jiao ◽  
...  
Keyword(s):  
Triticum Aestivum ◽  
Acetic Acid ◽  
Indole Acetic Acid ◽  
Expression Profiles ◽  
Functional Characterization ◽  
Tissue Expression ◽  
Wild Type ◽  
Gene Structures ◽  
Wheat Mutant

Tillering is a key agronomy trait for wheat (Triticum aestivum L.) production. Previously, we have reported a dwarf-monoculm wheat mutant (dmc) obtained from cultivar Guomai 301 (wild type, WT), and found growth regulating factors (GRFs) playing important roles in regulating wheat tillering. This study is to systematically investigate the roles of all the wheat GRFs (T. aestivum GRFs, TaGRFs) in regulating tillering, and screen out the key regulators. A total of 30 TaGRFs were identified and their physicochemical properties, gene structures, conserved domains, phylogenetic relationships and tissue expression profiles were analyzed. The expression levels of all the TaGRFs were significantly lower in dmc than those in WT at early tillering stage, and the abnormal expressions of TaGRF2-7(A, B, D), TaGRF5-7D, TaGRF10-6(A, B, D) and TaGRF11-2A were major causes constraining the tillering of dmc. The transcriptions of TaGRFs were significantly affected by exogenous indole acetic acid (IAA) and gibberellin acid (GA3) applications, which suggested that TaGRFs as well as IAA, GA signaling were involved in controlling wheat tillering. This study provided valuable clues for functional characterization of GRF genes in wheat.

Changes in adipokine expression during food deprivation in the mouse and the relationship to fasting-induced insulin resistance

2003 ◽  
Vol 81 (10) ◽  
pp. 979-985 ◽  
Author(s):  
Yaoting Gui ◽  
Josef V Silha ◽  
Suresh Mishra ◽  
Liam J Murphy
Keyword(s):  
Insulin Resistance ◽  
Food Deprivation ◽  
Tissue Expression ◽  
Brown Fat ◽  
Mrna Abundance ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Plasma Leptin

We investigated the changes in insulin resistance and adipose tissue expression of the adipokines resistin, adiponectin, and leptin and the transcription factors peroxisome proliferator-activated receptor-γ (PPAR-γ) and retinoid X receptor-α (RXR-α) during 48 h of food deprivation. Insulin sensitivity (SI) declined, whereas glucose effectiveness (SG) increased. Plasma adiponectin levels declined in the first 8 h and remained constant thereafter. There was no correlation between either SI or SG and adiponectin protein or mRNA levels. PPAR-γ mRNA abundance remained constant, whereas leptin and resistin mRNAs and plasma leptin declined and RXR-α mRNA abundance increased in both white and brown fat. Leptin mRNA abundance was closely correlated with SI (R2 = 0.91 and 0.87 for white and brown fat, respectively). Resistin mRNA abundance correlated inversely with SG (R2 = 0.99 and 0.84 for white and brown fat, respectively). These data indicate that changes in the expression of leptin are more closely correlated with the insulin resistance of fasting than with changes in other adipokines or RXR-α and PPAR-γ expression.Key words: insulin resistance, fasting, adipokines, resistin, leptin, adiponectin.

scholarly journals Chlorogenic Acid Functions as a Novel Agonist of PPARγ2 during the Differentiation of Mouse 3T3-L1 Preadipocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Shu-guang Peng ◽  
Yi-lin Pang ◽  
Qi Zhu ◽  
Jing-he Kang ◽  
Ming-xin Liu ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
Fruits And Vegetables ◽  
Quantitative Polymerase Chain Reaction ◽  
Lipid Synthesis ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Related Gene ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Impact

Rosiglitazone (RG) is a well-known activator of peroxisome proliferator-activated receptor-gamma (PPARγ) and used to treat hyperglycemia and type 2 diabetes; however, its clinical application has been confounded by adverse side effects. Here, we assessed the roles of chlorogenic acid (CGA), a phenolic secondary metabolite found in many fruits and vegetables, on the differentiation and lipolysis of mouse 3T3-L1 preadipocytes. The results showed that CGA promoted differentiation in vitro according to oil red O staining and quantitative polymerase chain reaction assays. As a potential molecular mechanism, CGA downregulated mRNA levels of the adipocyte differentiation-inhibitor gene Pref1 and upregulated those of major adipogenic transcriptional factors (Cebpb and Srebp1). Additionally, CGA upregulated the expression of the differentiation-related transcriptional factor PPARγ2 at both the mRNA and protein levels. However, following CGA intervention, the accumulation of intracellular triacylglycerides following preadipocyte differentiation was significantly lower than that in the RG group. Consistent with this, our data indicated that CGA treatment significantly upregulated the expression of lipogenic pathway-related genes Plin and Srebp1 during the differentiation stage, although the influence of CGA was weaker than that of RG. Notably, CGA upregulated the expression of the lipolysis-related gene Hsl, whereas it did not increase the expression of the lipid synthesis-related gene Dgat1. These results demonstrated that CGA might function as a potential PPARγ agonist similar to RG; however, the impact of CGA on lipolysis in 3T3-L1 preadipocytes differed from that of RG.

scholarly journals Effect of Chronic Valproic Acid Treatment on Hepatic Gene Expression Profile inWfs1Knockout Mouse

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Marite Punapart ◽  
Mall Eltermaa ◽  
Julia Oflijan ◽  
Silva Sütt ◽  
Anne Must ◽  
...  
Keyword(s):  
Gene Expression ◽  
Valproic Acid ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Expression Profiles ◽  
Peroxisome Proliferator ◽  
Hepatic Gene Expression ◽  
Wild Type ◽  
Drug Induced

Valproic acid (VPA) is a widely used anticonvulsant and mood-stabilizing drug whose use is often associated with drug-induced weight gain. Treatment with VPA has been shown to upregulateWfs1expressionin vitro. Aim of the present study was to compare the effect of chronic VPA treatment in wild type (WT) andWfs1knockout (KO) mice on hepatic gene expression profile. Wild type,Wfs1heterozygous, and homozygous mice were treated with VPA for three months (300 mg/kg i.p. daily) and gene expression profiles in liver were evaluated using Affymetrix Mouse GeneChip 1.0 ST array. We identified 42 genes affected byWfs1genotype, 10 genes regulated by VPA treatment, and 9 genes whose regulation by VPA was dependent on genotype. Among the genes that were regulated differentially by VPA depending on genotype was peroxisome proliferator-activated receptor delta (Ppard), whose expression was upregulated in response to VPA treatment in WT, but not inWfs1KO mice. Thus, regulation ofPpardby VPA is dependent onWfs1genotype.

scholarly journals The role of the amino-terminal domain in the interaction of unliganded peroxisome proliferator-activated receptor γ-2 with nuclear receptor co-repressor

2010 ◽  
Vol 45 (3) ◽  
pp. 133-145 ◽  
Author(s):  
Sadako Suzuki ◽  
Shigekazu Sasaki ◽  
Hiroshi Morita ◽  
Yutaka Oki ◽  
Daisuke Turiya ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Nuclear Receptor ◽  
Thyroid Hormone Receptor ◽  
Dominant Negative ◽  
Peroxisome Proliferator ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Amino Terminal

Peroxisome proliferator-activated receptor γ-2 (PPARG2) is a ligand-dependent transcriptional factor involved in the pathogenesis of insulin resistance. In the presence of a ligand, PPARG2 associates with co-activators, while it recruits co-repressors (CoRs) in the absence of a ligand. It has been reported that the interaction of liganded PPARG2 with co-activators is regulated by the amino-terminal A/B domain (NTD) via inter-domain communication. However, the role of the NTD is unknown in the case of the interaction between unliganded PPARG2 and CoRs. To elucidate this, total elimination of the influence of ligands is required, but the endogenous ligands of PPARG2 have not been fully defined. PPARG1-P467L, a naturally occurring mutant of PPARG1, was identified in a patient with severe insulin resistance. Reflecting its very low affinity for various ligands, this mutant does not have transcriptional activity in the PPAR response element, but exhibits dominant negative effects (DNEs) on liganded wild-type PPARG2-mediated transactivation. Using the corresponding PPARG2 mutant, PPARG2-P495L, we evaluated the role of the NTD in the interaction between unliganded PPARG2 and CoRs. Interestingly, the DNE of PPARG2-P495L was increased by the truncation of its NTD. NTD deletion also enhanced the DNE of a chimeric receptor, PT, in which the ligand-binding domain of PPARG2 was replaced with that of thyroid hormone receptor β-1. Moreover, NTD deletion facilitated the in vitro binding of nuclear receptor CoR with wild-type PPARG2, mutant P495L, and the PT chimera (PPARG2-THRB). Inter-domain communication in PPARG2 regulates not only ligand-dependent transactivation but also ligand-independent silencing.

Sign in / Sign up

Export Citation Format

Share Document