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REVIEW ARTICLE
Year : 2011  |  Volume : 2  |  Issue : 4  |  Page : 236-240  

The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases


Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India

Date of Web Publication16-Dec-2011

Correspondence Address:
Sandeep Tyagi
Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab - 142 001
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2231-4040.90879

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   Abstract 

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of nuclear hormone receptor superfamily comprising of the following three subtypes: PPARα, PPARγ, and PPARβ/δ. Activation of PPAR-α reduces triglyceride level and is involved in regulation of energy homeostasis. Activation of PPAR-γ causes insulin sensitization and enhances glucose metabolism, whereas activation of PPAR- β/δ enhances fatty acids metabolism. Thus, PPAR family of nuclear receptors plays a major regulatory role in energy homeostasis and metabolic function. The present review critically analyzes the protective and detrimental effect of PPAR agonists in dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity.

Keywords: Diabetes, dyslipidemia, peroxisome proliferator-activated receptors


How to cite this article:
Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res 2011;2:236-40

How to cite this URL:
Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res [serial online] 2011 [cited 2018 Nov 18];2:236-40. Available from: http://www.japtr.org/text.asp?2011/2/4/236/90879


   Introduction Top


Peroxisomes are subcellular organelles found in most plant and animal cells that perform diverse metabolic functions including H 2 O 2-based respiration, β-oxidation of fatty acids (FAs), and cholesterol metabolism. Peroxisome proliferator-activated receptors (PPARs) proteins belong to superfamily of phylogenetically related protein termed nuclear hormone factor.[1] PPARs were identified in rodents in 1990 and these belong to a nuclear hormone receptor superfamily containing 48 members. But, these agents are associated with no proliferation in the human beings. Structurally, PPARs are similar to steroid or thyroid hormone receptor and are stimulated in response to small lipophilic ligands. In rodents, a large class of structurally related chemicals including herbicides, industrial solvents, and hypolipidemic drugs lead to significant increase in the number and size of peroxisomes in the liver and may cause liver hypertrophy, liver hyperplasia, hepatocarcinogenesis, and transcription of genes encoding proximal enzymes. PPARs mainly exist in three subtypes; α, β/δ, and γ, each of which mediates the physiological actions of a large variety of FAs and FA-derived molecules. Activated PPARs are also capable of transcriptional repression through DNA-independent protein-protein interactions with other transcription factors such as NFκB signal activators and transducers of transcription STAT-1 and AP-1 signaling. [2]


   Structure Top


The PPARs possess the canonical domain structure common to other nuclear receptor family members, including the amino-terminal AF-1 trans activation domain, followed by a DNA-binding domain, and a dimerization and ligand-binding domain with a ligand-dependent trans activation function AF-2 located at the carboxy-terminal region. [3]


   Isoforms of Peroxisome Proliferator-Activated Receptors Top


PPARs are transcription factors that belong to the Superfamily of nuclear receptors. Other members of this family include retinoic acid, estrogen, thyroid, vitamin D, and glucocorticoid receptors, and several other proteins involved in xenobiotic metabolism PPARs act on DNA response elements as heterodimers with the retinoid X receptor (RXR). Their natural activating ligands are lipid-derived substrates. The family of PPARs is represented by the following three members: PPAR-α, PPAR-δ, and PPAR-γ. They play an essential role in energy metabolism; however, they differ in the spectrum of their activity-PPAR-γ regulates energy storage, whereas PPAR-α is expressed predominantly in the liver, and to a lesser extent, in muscle, in the heart, and in bone and PPAR-δ present ubiquitously expressed in whole body regulate energy expenditure; expression of PPAR-γ in endothelial cells, vascular smooth muscle cells. PPAR-γ is further subdivided in four isoforms.[4]

  • γ1 - expressed in virtually all tissues, including heart, muscle, colon, kidney, pancreas, and spleen.
  • γ2 - expressed mainly in adipose tissue (30 amino acids longer).
  • γ3 - expressed in macrophages, large intestine, and white adipose tissue.
  • γ4 - expressed in endothelial cells.



   Mechanism of Action of Peroxisome Proliferator-Activated Receptors Top


PPARs function as heterodimer in association with co- activator complex that binds to DNA sequence termed peroxisome proliferators response elements (PPREs) present in promoter of target genes which leads to transactivation and transrepression of various genes. [1] In the absence of the ligands, these heterodimers are associated with co- repressor complex which block gene transcription. Some of the agonists of various PPARs receptors are given in Balakumar P.2007. [5] Like PPARs, RXR exists as three distinct isoforms: RXR-α, β, and γ, all of which are activated by the endogenous agonist 9-cis retinoic acid. [6] No specific roles have yet been elaborated for these different isoforms within the PPAR: RXR complex. However, synthetic RXR agonists (rexiniids) can activate the complex and thereby obtain antidiabetic outcomes similar to those seen with PPAR agonists in mouse models of type 2 diabetes. [7] The LBD facilitates the heterodimerization of PPARs with RXR and the resultant heterodimer subsequently binds to PPRE with the recruitment of cofactors. [1]

Peroxisome Proliferator-Activated Receptor-Alpha

PPAR-α expression is relatively high in hepatocytes, enterocytes, vascular and immune cell types such as monocytes/macrophages, endothelial cells, smooth muscle cells, lymphocytes, non-neuronal cells like microglia and astroglia.[8],[9] In the liver, it plays a crucial role in FA oxidation, which provides energy for peripheral tissues, elevated mitochondrial and peroxisomal FAs β-oxidation rates, such as liver, heart muscle, kidney, skeletal muscle, retina, and brown adipose tissues, and have a potential role in oxidant/antioxidant pathway. [10],[11] PPAR-α ligands can be both synthetic or endogenous FAs and FA-derived compounds are natural ligands for PPAR-α. [12] Over the last several decades, there have been a number of studies on the physiology, pharmacology, and functional genomics of PPAR-α. In vivo and In vitro studies demonstrate that PPAR-α plays a central role in lipid and lipoprotein metabolism, and thereby decreases dyslipidemia associated with metabolic syndrome.[13],[14],[15] In the fasting state, PPAR-α is activated by adipose-derived FAs, thereby enhancing the generation of ketone bodies through FA oxidation in liver and peripheral blood mononuclear cells.[16]

Peroxisome Proliferator-Activated Receptor-γ

Thiazolidinediones (TZDs) are the most widely studied PPAR-γ ligands. Troglitazone was the first drug approved for this use, followed by rosiglitazone and pioglitazone. The mechanism of action of TZDs was not known until 1995, when Lehmann reported that TZDs were high affinity ligands, for Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-dependent transcription factor and a member of the nuclear receptor superfamily. Acting as sensors of hormones, vitamins, endogenous metabolites, and xenobiotic compounds, the nuclear receptors control the expression of a very large number of genes. PPAR-γ has been known for some time to regulate adipocyte differentiation, FA storage and glucose metabolism, and is a target of antidiabetic drugs.[17] PPAR-γ agonist improves insulin resistance by opposing the effect of TNF-α in adipocytes.[18] PPAR-γ enhances the expression of a number of genes encoding proteins involved in glucose and lipid metabolism.[19] Various modulator of PPAR-γ agonist is shown in Balakumar P. 2007.[5]

Peroxisome Proliferator-Activated Receptor-β/δ


PPAR-δ/β is expressed in skeletal muscle, adipocytes, macrophages, lungs, brain, and skin. It promotes FA metabolism and suppresses macrophage derived inflammation.[20] Newly synthesized compounds such as GW501516, GW610742, and GW0742X are shown to have high selectivity to PPARδ.[21] PPAR-δ has been noted to reduce the expression of inflammatory mediators and adhesion molecules, suggesting their potential role in attenuating atherogenesis.[22] Few studies have shown that PPAR-δ ligands have the potential to inhibit cardiac hypertrophy due to their inhibitory activity on NFκB, a transcription factor which produces inflammatory cytokines. Various modulator of PPAR-β/δ agonist is shown in Balakumar P. 2007. [5]


   Pharmacological Potentials Top


Obesity

This special issue begins with a review of key observations in human subjects harboring genetic variations in PPARγ and a thorough overview of the metabolic effects of PPARs in genetically modified animal models. The interaction of PPARs with uncoupling proteins regulating energy expenditure is reviewed as recent developments with RXR agonists. A closely related topic addressed is the molecular and physiological functions of PPAR co-activators and co-repressors in relationship to adipocyte energy metabolism. In addition, the potential advantages of selective PPAR agonists are discussed. The intriguing possibility that PPARs may mediate effects of caloric restriction on longevity is also considered. Finally, evidence that PPARs may be interesting therapeutic targets to modulate obesity-induced inflammation is reviewed. [23] PPAR-α ligands such as fibrates have been used for the treatment of dyslipidemia due to their ability to lower plasma triglyceride levels and elevate HDL cholesterol levels. PPAR-α activators have been shown to regulate obesity in rodents by both increasing hepatic FA oxidation and decreasing the levels of circulating triglycerides responsible for adipose cell hypertrophy and hyperplasia. However, these effects of PPAR-α on obesity and lipid metabolism may be exerted with sexual dimorphism and seem to be influenced by estrogen. Estrogen inhibits the actions of PPARα on obesity and lipid metabolism through its effects on PPARα-dependent regulation of target genes. [24]

Inflammation

Inflammatory conditions are mainly characterized by activation of macrophages and monocytes at the injury site which subsequently increase the release of proinflammatory mediators like TNF-α, IL-6, and IL-1β which in turn stimulates the production of COX products. PPAR-α and fenofibrate reduces pain and inflammation and further inhibits the release of several pro-inflammatory and pro-angiogenic enzymes (e.g., iNOS, chymase, and metalloproteinase MMP-9), and mediators (e.g., NO and TNF-α).[25],[26] More recently, PPAR-γ has been recognized as playing a fundamentally important role in the immune response through its ability to inhibit the expression of inflammatory cytokines and to direct the differentiation of immune cells toward anti-inflammatory phenotypes. A feature of PPAR-γ is the structural diversity of its ligands, which encompass endogenous metabolites, dietary compounds, and synthetic drugs. The high and increasing incidence of inflammatory and allergic disease, coupled with encouraging results from recent clinical trials, suggest that natural PPAR-γ agonists found in foods may be beneficial to human health by acting as anti-inflammatory molecules. PPAR-γ is therefore not only a target of the pharmaceutical industry, but also of great potential interest to the food industry, since it is activated by several natural dietary constituents. [27]

Adipocyte Differentiation

Adipogenesis refers to the process of differentiation of the pre-adipocyte precursor cells into adipocytes that are capable of lipid filling, as well as the expression of hormones and cytokines. PPAR-γ regulates the expression of numerous genes involved in lipid metabolism, including aP2, PPCK, acyl-CoA synthase, and LPL. [28] PPAR-γ has also been shown to control expression of FATP-1 and CD36, both involved in lipid uptake into adipocytes. These genes have all been shown to possess PPREs within their regulatory regions. PPAR-γ is mainly involved in the process of cell growth arrest, followed by progression into the fully differentiated adipocyte phenotype.[29] PPAR-γ and PPAR-β have both been implicated in molecular signaling that mediates adipocyte differentiation, whereas the role of PPAR-γ is well established in this process. The specific role of PPAR-γ is less certain. It has been reported that in the presence of standard differentiation medium, PPAR-γ is required for maximal adipocyte differentiation as PPAR-γ null adipocytes exhibit significantly impaired lipid accumulation and expression of adipose differentiate marker mRNAs.[30]

Anti-Cancer Effect

Peroxisome proliferator-activated receptor (PPAR) is a Double-Edged Sword in Cancer Therapy. PPAR-alpha stimulation appears to inhibit proliferation of human colon cancer cell lines and to reduce poly formation in the mouse model of familial adenomatous. PPAR-β (also referred to as PPARδ) in epithelial homeostasis have been described including the regulation of keratinocyte differentiation, apoptosis and cell proliferation, inflammation, and wound healing. [31] PPAR-γ not only controls the expression of genes involved in differentiations but also negatively regulates the cell cycle. [32] TZDs induce the tumor suppressor gene PTEN, which also contributes to their antiproliferative activity. PPAR-γ activation inhibits the proliferation of malignant cells, including those derived from liposarcoma, breast adenocarcinoma,[33] prostate carcinoma, colorectal carcinoma, non-small-cell lung carcinoma, pancreatic carcinoma, bladder cancer, gastric carcinoma, and glial tumors of the brain. [34]

Neurodegenerative Disorder

PPAR-γ agonists have also shown efficacy in Parkinson disease, Alzheimer disease, brain injury, and ALS. They act on microglial cells and inhibit the microglial cells activation. The role of PPARs in modulating lipid and glucose metabolism is well established. More recently, PPARs have been demonstrated to modulate inflammation. For example, PPAR agonists inhibit the production of proinflammatory molecules by peripheral immune cells as well as resident glial cells. Furthermore, PPAR receptor agonists have proven effective in suppressing the development of animal models of CNS inflammatory and neurodegenerative disorders. [35] In vivo oral administration of the PPAR-γ agonist pioglitazone reduced glial activation and the accumulation of Aβ-positive plaques in the hippocampus and cortex. Various neurodegenerative diseases are associated with electron transport chain enzyme activity reductions and increased mitochondrial-generated oxidative stress. [36]


   Peroxisome Proliferator-Activated Receptors in Lung Pathophysiology and Disease Top


This special issue contains a comprehensive group of reviews and original investigations illustrating the pivotal role of PPARs in the regulation of multiple cellular events in lung pathogenesis. Such events include lung morphogenesis, the inhibition of the release of inflammatory mediators from lung immune and stromal/parenchymal cells In vitro, and dampening both inflammation and damage in animal models of acute lung injury (ALI), ischemia-reperfusion injury, and allergic airways inflammation. Also covered are lung tissue remodeling and the fibro-proliferation that occur in chronic airways disease, ALI, pulmonary vascular disease, and pulmonary fibrosis. In addition, activation of key macrophage antimicrobial and reparative responses within the airspace is addressed, also data illuminating the central role of PPAR-γ in the regulation of critical aspects of lung tumor initiation, progression, and metastasis are summarized. [23]

Peroxisome Proliferator-Activated Receptors and Diabetes

The three PPAR subtypes, alpha, gamma, and delta, have distinct expression patterns and regulate glucose homeostasis based on the need of a specific tissue. Although PPAR alpha potentiates FA catabolism in the liver and is the molecular target of the lipid-lowering fibrates, PPAR-gamma is essential for adipocyte differentiation and hypertrophy, and mediates the activity of the insulin-sensitizing TZDs. PPAR-delta may be important in regulating body weight and lipid metabolism in fat tissues. [37]

Peroxisome Proliferator-Activated Receptors and Pain

Synthetic PPAR-α receptor agonists produce broad-spectrum analgesia in a dose-dependent manner.[38] It was recently reported that supraspinal (intracerebroventricular) administration of PPAR-α ligands (perfluorooctanoic acid) reduced peripheral edema and/or inflammatory hyperalgesia [25],[39],[40] and that intrathecal administration of PPARγ ligands, rosiglitazone and 15d-PGJ2, reduced behavioral signs of neuropathic pain.[41] It was recently reported that systemic administration of pioglitazone reduced behavioral signs of neuropathic pain, raising the possibility that this FDA-approved drug can be effective as an analgesic agent. [42]


   Conclusion Top


PPAR are involved in various independent and DNA-dependent molecular and enzymatic pathways in adipose tissue, liver, and skeletal muscles. These pathways are affected in disease condition and cause the metabolic energy imbalance. Thus, intervention of PPAR can provide therapeutic targets for plethora of diseases such as dyslipidemia, diabetes, obesity, inflammation, neurodegenerative disorder, and cancer. Finally, evidence that PPARs may be interesting therapeutic targets to modulate obesity-induced inflammation is reviewed. Since its inception, a little over three years ago, PPAR Research has become a vibrant forum showcasing global effort in this ever-expanding field of research. Then, there is a series of reviews focusing on the potentially beneficial effects of PPAR agonists on the various diseases. Examining the contents of these special issues reveals an intense interest in exploring new physiological roles of the PPARs and in the identification of new and improved PPAR agonist drugs.


   Acknowledgments Top


The authors are thankful to R. D. Budhiraja (director administration) ISF College of Pharmacy, Moga, Punjab for encouragement and valuable advice.

 
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Toxicological Sciences. 2018;
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12 Peroxisome Proliferator Activated Receptor Agonists Modulate Transposable Element Expression in Brain and Liver
Laura B. Ferguson,Lingling Zhang,Shi Wang,Courtney Bridges,R. Adron Harris,Igor Ponomarev
Frontiers in Molecular Neuroscience. 2018; 11
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13 Heme oxygenase-1 induction by rosiglitazone via PKCa/AMPKa/p38 MAPKa/SIRT1/PPAR? pathway suppresses lipopolysaccharide-mediated pulmonary inflammation
Rou-Ling Cho,Wei-Ning Lin,Chen-yu Wang,Chien-Chung Yang,Li-Der Hsiao,Chih-Chung Lin,Chuen-Mao Yang
Biochemical Pharmacology. 2018;
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14 H 2 S induces Th1/Th2 imbalance with triggered NF-?B pathway to exacerbate LPS-induce chicken pneumonia response
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Chemosphere. 2018; 208: 241
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15 Pivotal Roles of Peroxisome Proliferator-Activated Receptors (PPARs) and Their Signal Cascade for Cellular and Whole-Body Energy Homeostasis
Shreekrishna Lamichane,Babita Dahal Lamichane,Sang-Mo Kwon
International Journal of Molecular Sciences. 2018; 19(4): 949
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16 Vascular smooth muscle cell proliferation as a therapeutic target. Part 1: molecular targets and pathways
Dongdong Wang,Pavel Uhrin,Andrei Mocan,Birgit Waltenberger,Johannes M. Breuss,Devesh Tewari,Judit Mihaly-Bison,Lukasz Huminiecki,Rafal R. Starzynski,Nikolay T. Tzvetkov,Jaroslaw Horbanczuk,Atanas G. Atanasov
Biotechnology Advances. 2018;
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17 Supplementation with Resveratrol and Curcumin Does Not Affect the Inflammatory Response to a High-Fat Meal in Older Adults with Abdominal Obesity: A Randomized, Placebo-Controlled Crossover Trial
Cécile Vors,Charles Couillard,Marie-Eve Paradis,Iris Gigleux,Johanne Marin,Marie-Claude Vohl,Patrick Couture,Benoît Lamarche
The Journal of Nutrition. 2018; 148(3): 379
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18 Inhibitory Effects of a Novel PPAR-? Agonist MEKT1 on Pomc Expression/ACTH Secretion in AtT20 Cells
Rehana Parvin,Erika Noro,Akiko Saito-Hakoda,Hiroki Shimada,Susumu Suzuki,Kyoko Shimizu,Hiroyuki Miyachi,Atsushi Yokoyama,Akira Sugawara
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19 The Role of PPAR and Its Cross-Talk with CAR and LXR in Obesity and Atherosclerosis
Pengfei Xu,Yonggong Zhai,Jing Wang
International Journal of Molecular Sciences. 2018; 19(4): 1260
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20 Saroglitazar reduces obesity and associated inflammatory consequences in murine adipose tissue
Durgesh Kumar,Umesh Kumar Goand,Sanchita Gupta,Kripa Shankar,Salil Varshney,Sujith Rajan,Ankita Srivastava,Abhishek Gupta,Achchhe Lal Vishwakarma,Anurag Kumar Srivastava,Anil N Gaikwad
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21 Research Advances in the Correlation between Peroxisome Proliferator-Activated Receptor-? and Digestive Cancers
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22 Phytol: A review of biomedical activities
Muhammad Torequl Islam,Eunüs S. Ali,Shaikh J. Uddin,Subrata Shaw,Md Amirul Islam,Md Iqbal Ahmed,Manik Chandra Shill,Utpal Kumar Karmakar,Nagendra Sastry Yarla,Ishaq N. Khan,Md Morsaline Billah,Magdalena D. Pieczynska,Gokhan Zengin,Clemens Malainer,Ferdinando Nicoletti,Diana Gulei,Ioana Berindan-Neagoe,Apostol Apostolov,Maciej Banach,Andy W.K. Yeung,Amr El-Demerdash,Jianbo Xiao,Prasanta Dey,Santosh Yele,Artur Józwik,Nina Strzalkowska,Joanna Marchewka,Kannan R.R. Rengasamy,Jaroslaw Horbanczuk,Mohammad Amjad Kamal,Mohammad S. Mubarak,Siddhartha K. Mishra,Jamil A. Shilpi,Atanas G. Atanasov
Food and Chemical Toxicology. 2018;
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23 Biotinylated PAMAM G3 dendrimer conjugated with celecoxib and/or Fmoc-l-Leucine and its cytotoxicity for normal and cancer human cell lines
Lukasz Uram,Aleksandra Filipowicz,Maria Misiorek,Natalia Pienkowska,Joanna Markowicz,Elzbieta Walajtys-Rode,Stanislaw Wolowiec
European Journal of Pharmaceutical Sciences. 2018; 124: 1
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24 Peroxisomes and cancer: The role of a metabolic specialist in a disease of aberrant metabolism
Michael S. Dahabieh,Erminia Di Pietro,Maïka Jangal,Christophe Goncalves,Michael Witcher,Nancy E. Braverman,Sonia V. del Rincón
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25 Synthesis and evaluation of an orally available “Y”-shaped biaryl peroxisome proliferator-activated receptor d agonist
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Bioorganic & Medicinal Chemistry. 2018;
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26 Effects of Resveratrol and Mangiferin on PPAR? and FALDH Gene Expressions in Adipose Tissue of Streptozotocin-Nicotinamide-Induced Diabetes in Rats
Purabi Sarkar,Ananya Bhowmick,Mohan Chandra Kalita,Sofia Banu
Journal of Dietary Supplements. 2018; : 1
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27 Cancer; an induced disease of twentieth century! Induction of tolerance, increased entropy and ‘Dark Energy’: loss of biorhythms (Anabolism v. Catabolism)
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Clinical and Translational Medicine. 2018; 7(1)
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28 Integrating Thyroid Hormone Signaling in Hypothalamic Control of Metabolism: Crosstalk Between Nuclear Receptors
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29 A Systems Biology Approach to Understanding the Pathophysiology of High-Grade Serous Ovarian Cancer: Focus on Iron and Fatty Acid Metabolism
Anna Konstorum,Miranda L. Lynch,Suzy V. Torti,Frank M. Torti,Reinhard C. Laubenbacher
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30 PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma
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31 Neuronal Lipid Metabolism: Multiple Pathways Driving Functional Outcomes in Health and Disease
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32 Relationship Between Circulating Fatty Acids and Fatty Acid Ethanolamide Levels After a Single 2-h Dietary Fat Feeding in Male Sprague–Dawley Rats
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33 Understanding mitochondrial biogenesis through energy sensing pathways and its translation in cardio-metabolic health
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34 Transcriptome Analysis of Three Sheep Intestinal Regions reveals Key Pathways and Hub Regulatory Genes of Large Intestinal Lipid Metabolism
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35 Selenium supplementation through Se-rich dietary matrices can upregulate the anti-inflammatory responses in lipopolysaccharide-stimulated murine macrophages
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36 The Myofibroblast: TGFß-1, A Conductor which Plays a Key Role in Fibrosis by Regulating the Balance between PPAR? and the Canonical WNT Pathway
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37 Rational screening of peroxisome proliferator-activated receptor-? agonists from natural products: potential therapeutics for heart failure
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38 Molecular factors involved in the hypolipidemic- and insulin-sensitizing effects of a ginger (Zingiber officinale Roscoe) extract in rats fed a high-fat diet
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39 Linking cortisol response with gene expression in fish exposed to gold nanoparticles
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40 Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of novel quinoxaline derivatives as potential PPAR? and SUR agonists
Mohammed K. Ibrahim,Ibrahim H. Eissa,Abdallah E. Abdallah,Ahmed M. Metwaly,M.M. Radwan,M.A. ElSohly
Bioorganic & Medicinal Chemistry. 2017; 25(4): 1496
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41 Altered Pathway Analyzer: A gene expression dataset analysis tool for identification and prioritization of differentially regulated and network rewired pathways
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42 Of mice and humans through the looking glass: “Reflections” on epigenetics of lipid metabolism
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43 Regulation of cell signaling pathways by dietary agents for cancer prevention and treatment
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44 Integrated in silico–in vitro screening of ovarian cancer peroxisome proliferator-activated receptor-? agonists against a biogenic compound library
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45 Bacaba phenolic extract attenuates adipogenesis by down-regulating PPAR? and C/EBPa in 3T3-L1 cells
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46 Roles of Peroxisome Proliferator-Activated Receptor Gamma on Brain and Peripheral Inflammation
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47 Host-mediated effects of phytonutrients in ruminants: A review
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48 Thermodynamics in cancers: opposing interactions between PPAR gamma and the canonical WNT/beta-catenin pathway
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49 Influence of energy exchange genes on lipid metabolism during pregnancy complicated by the development of fetal growth restriction
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50 Ligands of peroxisome proliferator-activated receptor-alpha promote glutamate transporter-1 endocytosis in astrocytes
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The International Journal of Biochemistry & Cell Biology. 2017; 86: 42
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51 Signaling pathways linking inflammation to insulin resistance
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52 Dose-dependent effects of peroxisome proliferator-activated receptors ß/d agonist on systemic inflammation after haemorrhagic shock
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53 Bazedoxifene and raloxifene protect neocortical neurons undergoing hypoxia via targeting ERa and PPAR-?
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54 A systems perspective on brown adipogenesis and metabolic activation
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55 RXR Ligands Negatively Regulate Thrombosis and Hemostasis
Amanda J. Unsworth,Gagan D. Flora,Parvathy Sasikumar,Alexander P. Bye,Tanya Sage,Neline Kriek,Marilena Crescente,Jonathan M. Gibbins
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56 Increased hepatic mitochondrial FA oxidation reduces plasma and liver TG levels and is associated with regulation of UCPs and APOC-III in rats
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57 Association Between Plasma N-Acylethanolamides and High Hemoglobin Concentration in Southern Peruvian Highlanders
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58 Adiponectin regulates AQP3 via PPARa in human hepatic stellate cells
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Biochemical and Biophysical Research Communications. 2017; 490(1): 51
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59 CBMG, a novel derivative of mansonone G suppresses adipocyte differentiation via suppression of PPAR? activity
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Chemico-Biological Interactions. 2017; 273: 160
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60 Identification and comparative analysis of the pearl oyster Pinctada fucata hemocytes microRNAs in response to Vibrio alginolyticus infection
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Genes & Genomics. 2017;
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61 Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism
Jose A. Caparrós-Martín,Ricky R. Lareu,Joshua P. Ramsay,Jörg Peplies,F. Jerry Reen,Henrietta A. Headlam,Natalie C. Ward,Kevin D. Croft,Philip Newsholme,Jeffery D. Hughes,Fergal O’Gara
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62 Comparative genome-wide methylation analysis of longissimus dorsi muscles between Japanese black (Wagyu) and Chinese Red Steppes cattle
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63 Treatment Strategies for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis
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64 Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: effects on hepatic peroxisome proliferator-activated receptor-gamma receptors
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Canadian Journal of Physiology and Pharmacology. 2017; : 1
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65 The mechanism of skin lipids influencing skin status
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66 Combination of Classifiers Identifies Fungal-Specific Activation of Lysosome Genes in Human Monocytes
João P. Leonor Fernandes Saraiva,Cristina Zubiria-Barrera,Tilman E. Klassert,Maximilian J. Lautenbach,Markus Blaess,Ralf A. Claus,Hortense Slevogt,Rainer König
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67 Peroxisome proliferator-activated receptor gamma (PPAR?) in brown trout: Interference of estrogenic and androgenic inputs in primary hepatocytes
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Environmental Toxicology and Pharmacology. 2016; 46: 328
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68 Endocrine Aspects of Environmental “Obesogen” Pollutants
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69 Inhibition of hypoxia-induced cyclooxygenase-2 by Korean Red Ginseng is dependent on peroxisome proliferator-activated receptor gamma
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70 Nuclear receptor function in skin health and disease: therapeutic opportunities in the orphan and adopted receptor classes
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71 Astragaloside IV, a Natural PPAR? Agonist, Reduces Aß Production in Alzheimer’s Disease Through Inhibition of BACE1
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72 Prenatal phthalate exposure: epigenetic changes leading to lifelong impact on steroid formation
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73 Marine-sulfated polysaccharides extract of Ulva armoricana green algae exhibits an antimicrobial activity and stimulates cytokine expression by intestinal epithelial cells
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74 Molecular mechanism of lipid-induced cardiac insulin resistance and contractile dysfunction
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75 Nanofiber scaffolds influence organelle structure and function in bone marrow stromal cells
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76 Instant rice made from white and pigmented giant embryonic rice reduces lipid levels and body weight in high fat diet-fed mice
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77 Anti-Obesity Effect of Pine Cone (Pinus koraiensis) Supercritical Extract in High-Fat Diet-Induced Obese Mice
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78 Potential effects of curcumin on peroxisome proliferator-activated receptor-?in vitroandin vivo
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79 PPAR Gamma in Neuroblastoma: The Translational Perspectives of Hypoglycemic Drugs
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80 Use of retinoic acid/aldehyde dehydrogenase pathway as potential targeted therapy against cancer stem cells
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81 Effects of tetramethylpyrazine from Chinese black vinegar on antioxidant and hypolipidemia activities in HepG2 cells
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Food and Chemical Toxicology. 2016;
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82 DHA-enriched fish oil upregulates cyclin-dependent kinase inhibitor 2A (P16INK) expression and downregulates telomerase activity without modulating effects of PPAR? Pro12Ala polymorphism in type 2 diabetic patients: A randomized, double-blind, placebo-controlled clinical trial
Omid Toupchian,Gity Sotoudeh,Anahita Mansoori,Shima Abdollahi,Seyyed Ali Keshavarz,Mahmoud Djalali,Ensieh Nasli-Esfahani,Ehsan Alvandi,Reza Chahardoli,Fariba Koohdani
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83 Mechanisms of Body Weight Reduction by Black Tea Polyphenols
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84 Novel hepatic microRNAs upregulated in human nonalcoholic fatty liver disease
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85 The increasingly complex regulation of adipocyte differentiation
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86 Nutrigenomics and Beef Quality: A Review about Lipogenesis
Marcio Ladeira,Jon Schoonmaker,Mateus Gionbelli,Júlio Dias,Tathyane Gionbelli,José Carvalho,Priscilla Teixeira
International Journal of Molecular Sciences. 2016; 17(6): 918
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87 Neurokinin-1 receptor inhibition reverses ischaemic brain injury and dementia in bilateral common carotid artery occluded rats: possible mechanisms
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88 Endocrine and metabolic impacts of warming aquatic habitats: differential responses between recently isolated populations of a eurythermal desert pupfish
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89 Low serum vitamin D-status, air pollution and obesity: A dangerous liaison
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90 The Ticking of the Epigenetic Clock: Antipsychotic Drugs in Old Age
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91 Evidence that activation of nuclear peroxisome proliferator-activated receptor alpha (PPARa) modulates sleep homeostasis in rats
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92 Screening and functional analysis of differentially expressed genes in chronic glomerulonephritis by whole genome microarray
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93 Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid ß-oxidation
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94 Antidiabetic properties of dietary flavonoids: a cellular mechanism review
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95 Eicosanoid pathway in colorectal cancer: Recent updates
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96 Critical role of PPAR? in water balance
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97 Inactivation of PPARß/d adversely affects satellite cells and reduces postnatal myogenesis
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98 Systemic PPAR? deletion causes severe disturbance in fluid homeostasis in mice
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99 Expression of metabolic sensing receptors in adipose tissues of periparturient dairy cows with differing extent of negative energy balance
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100 Proliferation and fission of peroxisomes — An update
Michael Schrader,Joseph L. Costello,Luis F. Godinho,Afsoon S. Azadi,Markus Islinger
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101 The role of microRNAs in bone remodeling
Dian Jing,Jin Hao,Yu Shen,Ge Tang,Mei-Le Li,Shi-Hu Huang,Zhi-He Zhao
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102 Potential Epigenetic Mechanism in Non-Alcoholic Fatty Liver Disease
Chao Sun,Jian-Gao Fan,Liang Qiao
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103 Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?
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Archives of Dermatological Research. 2015; 307(9): 767
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104 Phosphatidic Acid (PA) can Displace PPARa/LXRa Binding to The EGFR Promoter Causing its Transrepression in Luminal Cancer Cells
Madhu Mahankali,Terry Farkaly,Shimpi Bedi,Heather A. Hostetler,Julian Gomez-Cambronero
Scientific Reports. 2015; 5: 15379
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105 Sleep and neurochemical modulation by the nuclear peroxisome proliferator-activated receptor a (PPAR-a) in rat
Stephanie Mijangos-Moreno,Alwin Poot-Aké,Khalil Guzmán,Gloria Arankowsky-Sandoval,Oscar Arias-Carrión,Jaime Zaldívar-Rae,Andrea Sarro-Ramírez,Eric Murillo-Rodríguez
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106 The role of PPAR?-mediated signalling in skin biology and pathology: new targets and opportunities for clinical dermatology
Yuval Ramot,Arianna Mastrofrancesco,Emanuela Camera,Pierre Desreumaux,Ralf Paus,Mauro Picardo
Experimental Dermatology. 2015; 24(4): 245
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107 Two butenolides with PPARa agonistic activity from a marine-derived Streptomyces
Yasuhiro Igarashi,Marumi Ikeda,Satoshi Miyanaga,Hiroaki Kasai,Yoshikazu Shizuri,Nobuyasu Matsuura
The Journal of Antibiotics. 2014;
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108 Anti-obesity Effects of African Mango (Irvingia gabonesis, IGOB 131TM) Extract in Leptin-deficient Obese Mice
Minhee Lee,Da-Eun Nam,Ok Kyung Kim,Tae Jin Shim,Ji Hoon Kim,Jeongmin Lee
Journal of the Korean Society of Food Science and Nutrition. 2014; 43(10): 1477
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109 Energy and metabolic sensing G protein-coupled receptors during lactation-induced changes in energy balance
P. Friedrichs,B. Saremi,S. Winand,J. Rehage,S. Dänicke,H. Sauerwein,M. Mielenz
Domestic Animal Endocrinology. 2014;
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110 MicroRNAs as key regulators of xenobiotic biotransformation and drug response
Jennifer Bolleyn,Joery De Kock,Robim Marcelino Rodrigues,Mathieu Vinken,Vera Rogiers,Tamara Vanhaecke
Archives of Toxicology. 2014;
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111 Deficiency of the Transcriptional Repressor B Cell Lymphoma 6 (Bcl6) Is Accompanied by Dysregulated Lipid Metabolism
Christopher R. LaPensee,Grace Lin,Alexander L. Dent,Jessica Schwartz,Xiaoli Chen
PLoS ONE. 2014; 9(6): e97090
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112 Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease
Vettickattuparambil George Giby,Thekkuttuparambil Ananthanarayanan Ajith
World Journal of Hepatology. 2014; 6(8): 570
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113 Mindin/Spondin 2 inhibits hepatic steatosis, insulin resistance, and obesity via interaction with peroxisome proliferator-activated receptor a in mice
Li-Hua Zhu,Aibing Wang,Pengcheng Luo,Xinan Wang,Ding-Sheng Jiang,Wei Deng,Xiaofei Zhang,Tao Wang,Yi Liu,Lu Gao,Shumin Zhang,Xiaodong Zhang,Jie Zhang,Hongliang Li
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114 PPARa ligand clofibrate ameliorates blood pressure and vascular reactivity in spontaneously hypertensive rats
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115 Polymorphism of FABP2 and PPARG2 genes in risk prediction of cataract among North Indian population
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116 A new dawn for the use of thiazolidinediones in cancer therapy
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117 Expression of PPAR-? in adipose tissue of rats with polycystic ovary syndrome induced by DHEA
YU-XIA WANG,WEI-JIE ZHU,BAO-GUO XIE
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118 PPAR-? inhibits IL-13-induced collagen production in mouse airway fibroblasts
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119 AMPK-dependent signaling modulates the suppression of invasion and migration by fenofibrate in CAL 27 oral cancer cells through NF-?B pathway
Shih-Chang Tsai,Ming-Hsui Tsai,Chang-Fang Chiu,Chi-Cheng Lu,Sheng-Chu Kuo,Nai-Wen Chang,Jai-Sing Yang
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120 Induction of Thymic Stromal Lymphopoietin Production by Nonanoic Acid and Exacerbation of Allergic Inflammation in Mice
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121 Therapeutic implications of targeting energy metabolism in breast cancer
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122 Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases
Monsalve, F.A. and Pyarasani, R.D. and Delgado-Lopez, F. and Moore-Carrasco, R.
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123 Hepatitis C virus nonstructural protein 5A favors upregulation of gluconeogenic and lipogenic gene expression leading towards insulin resistance: a metabolic syndrome
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124 The G32E Functional Variant Reduces Activity of PPARD by Nuclear Export and Post-Translational Modification in Pigs
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125 Liver damage is not reversed during the lean period in diet-induced weight cycling in mice
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126 SERPINA3K induces apoptosis in human colorectal cancer cells via activating the Fas/FasL/caspase-8 signaling pathway
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127 Interferon regulatory factor 9 protects against hepatic insulin resistance and steatosis in male mice
Xin-An Wang,Ran Zhang,Dingsheng Jiang,Wei Deng,Shumin Zhang,Shan Deng,Jinfeng Zhong,Tao Wang,Li-Hua Zhu,Li Yang,Shufen Hong,Sen Guo,Ke Chen,Xiao-Fei Zhang,Zhigang She,Yingjie Chen,Qinglin Yang,Xiao-Dong Zhang,Hongliang Li
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128 Peroxisome Proliferator-Activated Receptor Targets for the Treatment of Metabolic Diseases
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129 Therapeutic Implications of Targeting Energy Metabolism in Breast Cancer
Meena K. Sakharkar,Babita Shashni,Karun Sharma,Sarinder K. Dhillon,Prabhakar R. Ranjekar,Kishore R. Sakharkar
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130 Fatty acids regulation of inflammatory and metabolic genes
Laureane N. Masi,Alice C. Rodrigues,Rui Curi
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131 Molecular evidence for the involvement of PPAR-d and PPAR-? in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma
Irene Paterniti,Daniela Impellizzeri,Rosalia Crupi,Rossana Morabito,Michela Campolo,Emanuela Esposito,Salvatore Cuzzocrea
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132 L-165,041, troglitazone and their combination treatment to attenuate high glucose-induced receptor for advanced glycation end products (RAGE) expression
Yao-Jen Liang,Jhin-Hao Jian,Chao-Yi Chen,Chia-Yu Hsu,Chin-Yu Shih,Jyh-Gang Leu
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133 SERPINA3K induces apoptosis in human colorectal cancer cells via activating the Fas/FasL/caspase-8 signaling pathway
Yao, Y. and Li, L. and Huang, X. and Gu, X. and Xu, Z. and Zhang, Y. and Huang, L. and Li, S. and Dai, Z. and Li, C. and Zhou, T. and Cai, W. and Yang, Z. and Gao, G. and Yang, X.
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134 Molecular evidence for the involvement of PPAR-δ and PPAR-γ in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma
Paterniti, I. and Impellizzeri, D. and Crupi, R. and Morabito, R. and Campolo, M. and Esposito, E. and Cuzzocrea, S.
Journal of Neuroinflammation. 2013; 10(20)
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135 PPARG Epigenetic Deregulation and Its Role in Colorectal Tumorigenesis
Lina Sabatino, Alessandra Fucci, Massimo Pancione, and Vittorio Colantuoni
PPAR Research. 2012; : Art-687492
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136 Anti-angiogenic treatment strategies for the therapy of endometriosis
Laschke MW, Menger MD
European Society of Human Reproduction and Embryology. 2012; 18(6): 682-702
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137 Identification of a Molecular Signature Underlying Inhibition of Mammary Carcinoma Growth by Dietary N-3 Fatty Acids
Weiqin Jiang, Zongjian Zhu, John N. McGinley, Karam El Bayoumy, Andrea Manni, Henry J. Thompson
Cancer Research. 2012; 72(15): 3795-3806
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138 “PPARs: Interference with Warburg’ Effect and Clinical Anticancer Trials,”
Joseph Vamecq, Jean-Marie Colet, Jean Jacques Vanden Eynde, Gilbert Briand, Nicole Porchet, Stéphane Rocchi,
PPAR Research. 2012; : Art-304760
[Pubmed]
139 Anti-angiogenic treatment strategies for the therapy of endometriosis
M. W. Laschke,M. D. Menger
Human Reproduction Update. 2012; 18(6): 682
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140 PPARG Epigenetic Deregulation and Its Role in Colorectal Tumorigenesis
Lina Sabatino,Alessandra Fucci,Massimo Pancione,Vittorio Colantuoni
PPAR Research. 2012; 2012: 1
[Pubmed] | [DOI]
141 PPARs: Interference with Warburg’ Effect and Clinical Anticancer Trials
Joseph Vamecq,Jean-Marie Colet,Jean Jacques Vanden Eynde,Gilbert Briand,Nicole Porchet,Stéphane Rocchi
PPAR Research. 2012; 2012: 1
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    Abstract
   Introduction
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    Isoforms of Pero...
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