scholarly journals Peroxisome Proliferator-Activated Receptor Alpha Target Genes

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-20 ◽  
Author(s):  
Maryam Rakhshandehroo ◽  
Bianca Knoch ◽  
Michael Müller ◽  
Sander Kersten
Keyword(s):  
Energy Homeostasis ◽  
Target Genes ◽  
Biological Function ◽  
Molecular Target ◽  
Peroxisome Proliferator ◽  
Biological Processes ◽  
Nutrient Metabolism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPARαserves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARαbinds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARαgoverns biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARαis directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPARαin lipid metabolism and other pathways through a detailed analysis of the different known or putative PPARαtarget genes. The emphasis is on gene regulation by PPARαin liver although many of the results likely apply to other organs and tissues as well.

scholarly journals Role of peroxisome proliferator-activated receptor-alpha in acute pancreatitis induced by cerulein

Immunology ◽  
2006 ◽  
Vol 0 (0) ◽  
pp. 060608033622005-??? ◽  
Author(s):  
Tiziana Genovese ◽  
Emanuela Mazzon ◽  
Rosanna Di Paola ◽  
Carmelo Muia ◽  
Concetta Crisafulli ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

scholarly journals Peroxisome Proliferator-Activated Receptor γ and PGC-1α in Cancer: Dual Actions as Tumor Promoter and Suppressor

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Seong-Hoon Yun ◽  
Sang-Heum Han ◽  
Joo-In Park
Keyword(s):  
Metabolic Pathways ◽  
Energy Homeostasis ◽  
Tumor Promoter ◽  
Clinical Implications ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
Action Mechanisms ◽  
Important Regulator

Peroxisome proliferator-activated receptor γ (PPARγ) is part of a nuclear receptor superfamily that regulates gene expression involved in cell differentiation, proliferation, immune/inflammation response, and lipid metabolism. PPARγ coactivator-1α (PGC-1α), initially identified as a PPARγ-interacting protein, is an important regulator of diverse metabolic pathways, such as oxidative metabolism and energy homeostasis. The role of PGC-1α in diabetes, neurodegeneration, and cardiovascular disease is particularly well known. PGC-1α is also now known to play important roles in cancer, independent of the role of PPARγ in cancer. Though many researchers have studied the expression and clinical implications of PPARγ and PGC-1α in cancer, there are still many controversies about the role of PPARγ and PGC-1α in cancer. This review examines and summarizes some recent data on the role and action mechanisms of PPARγ and PGC-1α in cancer, respectively, particularly the recent progress in understanding the role of PPARγ in several cancers since our review was published in 2012.

scholarly journals Gene Expression Profiling Reveals That PXR Activation Inhibits Hepatic PPARα Activity and Decreases FGF21 Secretion in Male C57Bl6/J Mice

2019 ◽  
Author(s):  
Sharon Ann Barretto ◽  
Frederic Lasserre ◽  
Anne Fougerat ◽  
Lorraine Smith ◽  
Tiffany Fougeray ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Target Genes ◽  
Pregnane X Receptor ◽  
Alpha Activity ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Metabolizing Enzymes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Xenobiotic Metabolizing Enzymes ◽  
Triglyceride Accumulation

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16α-carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes mostly xenobiotic metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor α (PPARα) signature. Comparison of this signature with a list of fasting-induced PPARα target genes confirmed that PXR activation decreased the expression of more than 25 PPARα target genes, among which the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPARα activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

scholarly journals Identification and Characterization of Cannabimovone, a Cannabinoid from Cannabis sativa, as a Novel PPARγ Agonist via a Combined Computational and Functional Study

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1119 ◽  
Author(s):  
Fabio Arturo Iannotti ◽  
Fabrizia De Maio ◽  
Elisabetta Panza ◽  
Giovanni Appendino ◽  
Orazio Taglialatela-Scafati ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Target Genes ◽  
Cannabis Sativa ◽  
Large Family ◽  
Bioactive Compound ◽  
Binding Mode ◽  
Functional Study ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist

Phytocannabinoids (pCBs) are a large family of meroterpenoids isolated from the plant Cannabis sativa. Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best investigated phytocannabinoids due to their relative abundance and interesting bioactivity profiles. In addition to various targets, THC and CBD are also well-known agonists of peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor involved in energy homeostasis and lipid metabolism. In the search of new pCBs potentially acting as PPARγ agonists, we identified cannabimovone (CBM), a structurally unique abeo-menthane pCB, as a novel PPARγ modulator via a combined computational and experimental approach. The ability of CBM to act as dual PPARγ/α agonist was also evaluated. Computational studies suggested a different binding mode toward the two isoforms, with the compound able to recapitulate the pattern of H-bonds of a canonical agonist only in the case of PPARγ. Luciferase assays confirmed the computational results, showing a selective activation of PPARγ by CBM in the low micromolar range. CBM promoted the expression of PPARγ target genes regulating the adipocyte differentiation and prevented palmitate-induced insulin signaling impairment. Altogether, these results candidate CBM as a novel bioactive compound potentially useful for the treatment of insulin resistance-related disorders.

scholarly journals PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice

2020 ◽  
Vol 21 (6) ◽  
pp. 2061 ◽  
Author(s):  
Yaping Wang ◽  
Takero Nakajima ◽  
Frank J. Gonzalez ◽  
Naoki Tanaka
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Liver Cancer ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolic Regulators

Peroxisome proliferator-activated receptor (PPAR) α, β/δ, and γ modulate lipid homeostasis. PPARα regulates lipid metabolism in the liver, the organ that largely controls whole-body nutrient/energy homeostasis, and its abnormalities may lead to hepatic steatosis, steatohepatitis, steatofibrosis, and liver cancer. PPARβ/δ promotes fatty acid β-oxidation largely in extrahepatic organs, and PPARγ stores triacylglycerol in adipocytes. Investigations using liver-specific PPAR-disrupted mice have revealed major but distinct contributions of the three PPARs in the liver. This review summarizes the findings of liver-specific PPAR-null mice and discusses the role of PPARs in the liver.

scholarly journals Targeting PPARα for the Treatment and Understanding of Cardiovascular Diseases

2018 ◽  
Vol 51 (6) ◽  
pp. 2760-2775 ◽  
Author(s):  
Shuzhen Li ◽  
Bingyu Yang ◽  
Yang Du ◽  
Yurui Lin ◽  
Jiaqi Liu ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Plasma Lipid ◽  
Renin Angiotensin System ◽  
Peroxisome Proliferator ◽  
Nutrient Metabolism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Safety Margins ◽  
Increased Risk

Three members of the peroxisome proliferator-activated receptor (PPAR) family, PPARα, PPARγ, and PPARβ/δ, have been investigated widely over the past few decades. Although the roles of these PPARs and their agonists/antagonists were defined in clinical and basic studies, the conflicting results from these studies indicate that more analysis is needed to understand the roles of PPARs. PPARα is a ligand-activated transcription factor that contributes to the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. In this review, we focus on the function and mechanisms of PPARα in the cardiovascular system under various pathological conditions, including vascular and heart injury, blood pressure regulation, and lipid disorder-related cardiovascular injury, as well as its polymorphisms and pharmacogenetic associations with cardiovascular diseases. The anti-inflammatory effect of PPARα in cardiovascular injury is mainly through inhibition of pro-inflammatory signaling pathways and improvement of the lipid profile. Moreover, PPARα also modulates the activity of endothelial nitric oxide synthase and resets the renin-angiotensin system to regulate vascular tone. PPARα gene variants appear to be associated with some cardiovascular risk factors, such as higher plasma lipid levels, cardiac growth, and increased risk of coronary artery disease. Nowadays, novel PPARα drugs with broad safety margins and therapeutic potential for metabolic syndrome and cardiovascular diseases are being developed and applied in the clinical setting. The insights from the current review shed new light on areas of further study and provide a better understanding of the role of PPARα in cardiovascular diseases.

scholarly journals Gene Expression Profiling Reveals that PXR Activation Inhibits Hepatic PPARα Activity and Decreases FGF21 Secretion in Male C57Bl6/J Mice

2019 ◽  
Vol 20 (15) ◽  
pp. 3767 ◽  
Author(s):  
Sharon Ann Barretto ◽  
Frédéric Lasserre ◽  
Anne Fougerat ◽  
Lorraine Smith ◽  
Tiffany Fougeray ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Target Genes ◽  
Pregnane X Receptor ◽  
Fibroblast Growth Factor 21 ◽  
Peroxisome Proliferator ◽  
Metabolizing Enzymes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Xenobiotic Metabolizing Enzymes ◽  
Triglyceride Accumulation ◽  
Transcriptomic Signature

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic-metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs. Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16α-carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes, mostly xenobiotic-metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor α (PPARα) signature. Comparison of this signature with a list of fasting-induced PPARα target genes confirmed that PXR activation decreased the expression of more than 25 PPARα target genes, among which was the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPARα activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

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