scholarly journals Glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors

2007 ◽  
Vol 64 (9) ◽  
pp. 1145-1157 ◽  
Author(s):  
S. Mandard ◽  
R. Stienstra ◽  
P. Escher ◽  
N. S. Tan ◽  
I. Kim ◽  
...  
Keyword(s):  
Target Gene ◽  
Glycogen Synthase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
Novel Target

scholarly journals The G0/G1 switch gene 2 is a novel PPAR target gene

2005 ◽  
Vol 392 (2) ◽  
pp. 313-324 ◽  
Author(s):  
Fokko Zandbergen ◽  
Stéphane Mandard ◽  
Pascal Escher ◽  
Nguan Soon Tan ◽  
David Patsouris ◽  
...  
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Target Gene ◽  
Mrna Level ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Wild Type ◽  
Hepatic Expression ◽  
Peroxisome Proliferator Activated Receptors ◽  
Novel Target ◽  
Responsive Element

PPARs (peroxisome-proliferator-activated receptors) α, β/δ and γ are a group of transcription factors that are involved in numerous processes, including lipid metabolism and adipogenesis. By comparing liver mRNAs of wild-type and PPARα-null mice using microarrays, a novel putative target gene of PPARα, G0S2 (G0/G1 switch gene 2), was identified. Hepatic expression of G0S2 was up-regulated by fasting and by the PPARα agonist Wy14643 in a PPARα-dependent manner. Surprisingly, the G0S2 mRNA level was highest in brown and white adipose tissue and was greatly up-regulated during mouse 3T3-L1 and human SGBS (Simpson–Golabi–Behmel syndrome) adipogenesis. Transactivation, gel shift and chromatin immunoprecipitation assays indicated that G0S2 is a direct PPARγ and probable PPARα target gene with a functional PPRE (PPAR-responsive element) in its promoter. Up-regulation of G0S2 mRNA seemed to be specific for adipogenesis, and was not observed during osteogenesis or myogenesis. In 3T3-L1 fibroblasts, expression of G0S2 was associated with growth arrest, which is required for 3T3-L1 adipogenesis. Together, these data indicate that G0S2 is a novel target gene of PPARs that may be involved in adipocyte differentiation.

MPC1 is essential for PGC-1α-induced mitochondrial respiration and biogenesis

2018 ◽  
Vol 475 (10) ◽  
pp. 1687-1699 ◽  
Author(s):  
Eunjin Koh ◽  
Young Kyung Kim ◽  
Daye Shin ◽  
Kyung-Sup Kim
Keyword(s):  
Target Gene ◽  
Peroxisome Proliferator ◽  
Mitochondrial Matrix ◽  
Strong Suppression ◽  
Mitochondrial Oxygen Consumption ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Renal Cell Carcinoma ◽  
Mitochondrial Pyruvate Carrier ◽  
Novel Target ◽  
Estrogen Related Receptor

Mitochondrial pyruvate carrier (MPC), which is essential for mitochondrial pyruvate usage, mediates the transport of cytosolic pyruvate into mitochondria. Low MPC expression is associated with various cancers, and functionally associated with glycolytic metabolism and stemness. However, the mechanism by which MPC expression is regulated is largely unknown. In this study, we showed that MPC1 is down-regulated in human renal cell carcinoma (RCC) due to strong suppression of peroxisome proliferator-activated receptor-gamma co-activator (PGC)-1 alpha (PGC-1α). We also demonstrated that overexpression of PGC-1α stimulates MPC1 transcription, while depletion of PGC-1α by siRNA suppresses MPC expression. We found that PGC-1α interacts with estrogen-related receptor-alpha (ERR-α) and recruits it to the ERR-α response element motif located in the proximal MPC1 promoter, resulting in efficient activation of MPC1 expression. Furthermore, the MPC inhibitor, UK5099, blocked PGC-1α-induced pyruvate-dependent mitochondrial oxygen consumption. Taken together, our results suggest that MPC1 is a novel target gene of PGC-1α. In addition, low expression of PGC-1α in human RCC might contribute to the reduced expression of MPC, resulting in impaired mitochondrial respiratory capacity in RCC by limiting the transport of pyruvate into the mitochondrial matrix.

scholarly journals PPARgene: A Database of Experimentally Verified and Computationally Predicted PPAR Target Genes

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Li Fang ◽  
Man Zhang ◽  
Yanhui Li ◽  
Yan Liu ◽  
Qinghua Cui ◽  
...  
Keyword(s):  
In Silico ◽  
Target Gene ◽  
Target Genes ◽  
Prediction Method ◽  
Peroxisome Proliferator ◽  
Physiological Processes ◽  
Peroxisome Proliferator Activated Receptors ◽  
High Throughput Gene Expression ◽  
Responsive Element ◽  
Target Gene Transcription

The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of the nuclear receptor superfamily. Upon ligand binding, PPARs activate target gene transcription and regulate a variety of important physiological processes such as lipid metabolism, inflammation, and wound healing. Here, we describe the first database of PPAR target genes, PPARgene. Among the 225 experimentally verified PPAR target genes, 83 are for PPARα, 83 are for PPARβ/δ, and 104 are for PPARγ. Detailed information including tissue types, species, and reference PubMed IDs was also provided. In addition, we developed a machine learning method to predict novel PPAR target genes by integratingin silicoPPAR-responsive element (PPRE) analysis with high throughput gene expression data. Fivefold cross validation showed that the performance of this prediction method was significantly improved compared to thein silicoPPRE analysis method. The prediction tool is also implemented in the PPARgene database.

scholarly journals Molecular Mechanisms and Genome-Wide Aspects of PPAR Subtype Specific Transactivation

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Anne Bugge ◽  
Susanne Mandrup
Keyword(s):  
Energy Homeostasis ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Fat Metabolism ◽  
Special Focus ◽  
Peroxisome Proliferator ◽  
Subtype Specificity ◽  
Genome Wide ◽  
Peroxisome Proliferator Activated Receptors

The peroxisome proliferator-activated receptors (PPARs) are central regulators of fat metabolism, energy homeostasis, proliferation, and inflammation. The three PPAR subtypes, PPAR, /, and activate overlapping but also very different target gene programs. This review summarizes the insights into PPAR subtype-specific transactivation provided by genome-wide studies and discusses the recent advances in the understanding of the molecular mechanisms underlying PPAR subtype specificity with special focus on the regulatory role of AF-1.

scholarly journals Peroxisome Proliferator-Activated Receptor γ Target Gene Encoding a Novel Angiopoietin-Related Protein Associated with Adipose Differentiation

2000 ◽  
Vol 20 (14) ◽  
pp. 5343-5349 ◽  
Author(s):  
J. Cliff Yoon ◽  
Troy W. Chickering ◽  
Evan D. Rosen ◽  
Barry Dussault ◽  
Yubin Qin ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Time Course ◽  
Target Gene ◽  
Target Genes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Isolation And Characterization ◽  
Adipose Differentiation ◽  
Novel Target

ABSTRACT The nuclear receptor peroxisome proliferator-activated receptor γ regulates adipose differentiation and systemic insulin signaling via ligand-dependent transcriptional activation of target genes. However, the identities of the biologically relevant target genes are largely unknown. Here we describe the isolation and characterization of a novel target gene induced by PPARγ ligands, termed PGAR (for PPARγ angiopoietin related), which encodes a novel member of the angiopoietin family of secreted proteins. The transcriptional induction of PGAR follows a rapid time course typical of immediate-early genes and occurs in the absence of protein synthesis. The expression of PGAR is predominantly localized to adipose tissues and placenta and is consistently elevated in genetic models of obesity. Hormone-dependent adipocyte differentiation coincides with a dramatic early induction of the PGAR transcript. Alterations in nutrition and leptin administration are found to modulate the PGAR expression in vivo. Taken together, these data suggest a possible role for PGAR in the regulation of systemic lipid metabolism or glucose homeostasis.

scholarly journals PPARs Integrate the Mammalian Clock and Energy Metabolism

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Lihong Chen ◽  
Guangrui Yang
Keyword(s):  
Energy Metabolism ◽  
Nuclear Receptors ◽  
Essential Role ◽  
Target Gene ◽  
Target Genes ◽  
Circadian Regulation ◽  
Peroxisome Proliferator ◽  
Mouse Tissues ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of numerous target genes. PPARs play an essential role in various physiological and pathological processes, especially in energy metabolism. It has long been known that metabolism and circadian clocks are tightly intertwined. However, the mechanism of how they influence each other is not fully understood. Recently, all three PPAR isoforms were found to be rhythmically expressed in given mouse tissues. Among them, PPARαand PPARγare direct regulators of core clock components, Bmal1 and Rev-erbα, and, conversely, PPARαis also a direct Bmal1 target gene. More importantly, recent studies using knockout mice revealed that all PPARs exert given functions in a circadian manner. These findings demonstrated a novel role of PPARs as regulators in correlating circadian rhythm and metabolism. In this review, we summarize advances in our understanding of PPARs in circadian regulation.

scholarly journals Thyroid hormone receptors regulate adipogenesis and carcinogenesis via crosstalk signaling with peroxisome proliferator-activated receptors

2009 ◽  
Vol 44 (3) ◽  
pp. 143-154 ◽  
Author(s):  
Changxue Lu ◽  
Sheue-Yann Cheng
Keyword(s):  
Thyroid Hormone ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptors ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Biological Impact ◽  
Hormone Response Elements ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) and thyroid hormone receptors (TRs) are members of the nuclear receptor superfamily. They are ligand-dependent transcription factors that interact with their cognate hormone response elements in the promoters to regulate respective target gene expression to modulate cellular functions. While the transcription activity of each is regulated by their respective ligands, recent studies indicate that via multiple mechanisms PPARs and TRs crosstalk to affect diverse biological functions. Here, we review recent advances in the understanding of the molecular mechanisms and biological impact of crosstalk between these two important nuclear receptors, focusing on their roles in adipogenesis and carcinogenesis.

The Role of Plant-Derived Compounds in Managing Diabetes Mellitus: A Review of Literature from 2014 To 2019

2020 ◽  
Vol 28 ◽  
Author(s):  
Heba A.S. El-Nashar ◽  
Nada M. Mostafa ◽  
Mohamed El-Shazly ◽  
Omayma A. Eldahshan
Keyword(s):  
Diabetes Mellitus ◽  
Glycogen Synthase ◽  
Direct Action ◽  
Tyrosine Phosphatase ◽  
Natural Compounds ◽  
Antidiabetic Activity ◽  
Peroxisome Proliferator ◽  
Dipeptidyl Peptidase 4 ◽  
Glut4 Expression ◽  
Sensitizing Effect

Background:: Diabetes mellitus (DM) represents a global health problem characterized by hyperglycemia due to insufficient insulin secretion or failure of insulin activity. There is an imperative need for the discovery of alternative therapeutic agents that overcome the drawbacks of the current synthetic antidiabetic drugs. Objectives:: This review critically summarizes the reports on the known and novel natural compounds including alkaloids, flavonoids, and saponins with a potent antidiabetic activity that were recently published from 2014 to 2019. We discussed the underlying mechanisms of action that put these compounds in the category of effective antidiabetic candidates. Methods: Information was obtained from Google Scholar, Scirus, PubMed, and Science Direct. Discussion and Conclusion:: The reported natural compounds showed promising antidiabetic activity through different mechanisms such as the inhibition of α-amylase, α-glucosidase, insulin-sensitizing effect, direct action on protein tyrosine phosphatase 1B (PTP1B), peroxisome proliferator-activated receptors (PPARs), GLUT4 expression, insulin receptor substrate- 1 (IRS-1) and glycogen synthase kinase-3β (GSK-3β) as well as dipeptidyl peptidase-4 (DPP-4) enzyme. Some compounds inhibited the formation of advanced glycation end products (AGEs). Other compounds prevented the risk of diabetic complications such as cardiovascular diseases, retinopathy, and nephropathy. This review provides a critical overview of the most recent discoveries of antidiabetic agents from natural sources. This overview could help researchers to focus on the most prominent candidates aiming to develop new drug leads.

Sign in / Sign up

Export Citation Format

Share Document