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Ppar gamma

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https://www.readbyqxmd.com/read/28539091/in-silico-identification-of-potential-drug-compound-against-peroxisome-proliferator-activated-receptor-gamma-by-virtual-screening-and-toxicity-studies-for-treatment-of-diabetic-nephropathy
#1
Smrita Singh, Aparajita Mohanty
Diabetic Nephropathy is a serious complication of Diabetes Mellitus. Current therapeutic strategies of Diabetic Nephropathy are based on control of modifiable risks like hypertension, glucose levels, and dyslipidemia. Peroxisome proliferator activated receptor-gamma (PPAR-γ) is implicated in several metabolic syndromes including Diabetic Nephropathy, besides obesity, insulin insensitivity, dislipidemia, inflammation and hypertension. In the present study, virtual screening of 617 compounds from two different public databases was done against PPAR- γ with an objective to find a possible lead compound...
May 24, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28534168/father-s-obesity-programs-the-adipose-tissue-in-the-offspring-via-the-local-renin-angiotensin-system-and-mapks-pathways-especially-in-adult-male-mice
#2
Fernanda Ornellas, Isabele Bringhenti, Brenda Akemi N F Mattos, Carlos Alberto Mandarim-de-Lacerda, Marcia Barbosa Aguila
PURPOSE: Studies demonstrated the influence of mother's obesity on offspring. However, the father is also related to programming the future generation. The study aimed to evaluate the effects of father's obesity upon white adipose tissue (WAT) remodeling, resulting in activation of signaling pathways and inflammation in male and female offspring. METHODS: Male C57BL/6 mice received control diet (lean father group; 17% energy from lipids) or high-fat diet (obese father group; 49% energy from lipids) for 8 weeks before mating...
May 22, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28534088/the-ppar-gamma-binding-sequence-pal3-is-necessary-for-basal-but-dispensable-for-high-fat-diet-regulated-human-renin-expression-in-the-kidney
#3
Peter Lachmann, Jenny Selbmann, Linda Hickmann, Bernd Hohenstein, Christian Hugo, Vladimir T Todorov
We reported earlier that PPAR-gamma regulates renin transcription through a human-specific atypical binding sequence termed hRen-Pal3. Here we developed a mouse model to investigate the functional relevance of the hRen-Pal3 sequence in vivo since it might be responsible for the increased renin production in obesity and thus for the development of accompanying arterial hypertension. We used bacterial artificial chromosome construct and co-placement strategy to generate two transgenic mouse lines expressing the human renin gene from identical genomic locus without affecting the intrinsic mouse renin expression...
May 22, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28529818/high-protein-fish-oil-diet-prevents-hepatic-steatosis-in-noncnzo10-mice-association-with-diet-genetics-regulated-micro-rnas
#4
Nikhil Adi, Jennipher Adi, Roberta Marques Lassance-Soares, Paul Kurlansky, Hong Yu, Keith A Webster
OBJECTIVE: NONcNZO10 (NZ10) mice are predisposed to obesity and develop type 2 diabetes (T2D) and hepatic steatosis even when maintained on a control diet (CD) of 6% fat. Studies were designed to determine whether this extreme susceptibility phenotype could be alleviated by diet and if so the molecular targets of diet. METHODS: NZ10 and SWR/J (SWR) control mice were fed a CD or a test diet of high protein and fish oil (HPO) for 19 weeks and then analyzed for steatosis, blood chemistry, hepatic gene and micro-RNA expression...
June 2016: Journal of Diabetes & Metabolism
https://www.readbyqxmd.com/read/28514832/anti-obesity-effects-of-tea-from-mangifera-indica-l-leaves-of-the-ub%C3%A3-variety-in-high-fat-diet-induced-obese-rats
#5
Natalia Medina Ramírez, Renata C Lopes Toledo, Maria E Castro Moreira, Hércia Stampini Duarte Martino, Laércio Dos Anjos Benjamin, José H de Queiroz, Andréia Queiroz Ribeiro, Sônia Machado Rocha Ribeiro
Due to the high content of bioactive compounds, herbal teas are being investigated as adjuvant in chronic disease management. Studies have shown that mango leaf tea contain mangiferin, total phenolics and antioxidants, compounds with many functional properties. Therefore, this study aims to evaluate the anti-obesity effects of tea from Mangifera indica L. leaves, Ubá variety (TML), in obese rats fed a high-fat diet (HFD). For this, adult male Wistar rats were divided into three groups (n=8): the control group (fed AIN-93 diet), obese group (fed a HFD) and treated group (fed a HFD and supplemented with TML for 8 weeks)...
May 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28503816/xanthophylls-increased-hdlc-level-and-nuclear-factor-ppar%C3%AE-rxr%C3%AE-and-rar%C3%AE-expression-in-hens-and-chicks
#6
Y-Y Gao, L Jin, H Peng, L-H Xu, Q-X Wang, J Ji, C-K Wang, Y-Z Bi
This study was designed to investigate effects of xanthophylls on serum lipid profile (triglyceride, TG; cholesterol, CHO; high-density lipoprotein cholesterol, HDLC; and low-density lipoprotein cholesterol, LDLC) and nuclear factor (peroxisome proliferator-activated receptor gamma, PPARγ; PPAR gamma coactivator 1 alpha, PGC1α; retinoid X receptor gamma, RXRγ; and retinoic acid receptor alpha, RARα) gene expression of breeding hens and chicks. In experiment 1, 432 hens were divided into three groups and fed diets supplemented with 0 (as control group), 20 or 40 mg/kg xanthophylls...
May 15, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28499821/x-ray-crystal-structure-of-rivoglitazone-bound-to-ppar%C3%AE-and-ppar-subtype-selectivity-of-tzds
#7
Harinda Rajapaksha, Harpreet Bhatia, Kate Wegener, Nikolai Petrovsky, John B Bruning
Thiazolidinedione (TZD) compounds targeting the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR) demonstrate unique benefits for the treatment of insulin resistance and type II diabetes. TZDs include rosiglitazone, pioglitazone and rivoglitazone, with the latter being the most potent. The TZDs are only marginally selective for the therapeutic target PPARγ as they also activate PPARα and PPARδ homologues to varying degrees, causing off-target effects. While crystal structures for TZD compounds in complex with PPARγ are available, minimal structural information is available for TZDs bound to PPARα and PPARδ...
May 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28498501/ppar-gamma-agonist-pioglitazone-modifies-craving-intensity-and-brain-white-matter-integrity-in-patients-with-primary-cocaine-use-disorder-a-double-blind-randomized-controlled-pilot-trial
#8
Joy M Schmitz, Charles E Green, Khader M Hasan, Jessica Vincent, Robert Suchting, Michael F Weaver, F Gerard Moeller, Ponnada A Narayana, Kathryn A Cunningham, Kelly T Dineley, Scott D Lane
BACKGROUND AND AIMS: Pioglitazone (PIO), a potent agonist of PPAR-gamma, is a promising candidate treatment for cocaine use disorder (CUD). We tested the effects of PIO on targeted mechanisms relevant to CUD: cocaine craving and brain white matter (WM) integrity. Feasibility, medication compliance, and tolerability were evaluated. DESIGN: Two-arm double-blind randomized controlled proof-of-concept pilot trial of PIO or placebo (PLC). SETTING: Single-site outpatient treatment research clinic in Houston, Texas, USA...
May 12, 2017: Addiction
https://www.readbyqxmd.com/read/28483651/unlike-ppargamma-neither-other-ppars-nor-pgc-1alpha-is-elevated-in-the-cerebrospinal-fluid-of-patients-with-multiple-sclerosis
#9
Levente Szalardy, Denes Zadori, Krisztina Bencsik, Laszlo Vecsei, Peter Klivenyi
Corroborating with prior experimental findings, we recently reported the pronounced elevation of peroxisome proliferator-activated receptor gamma (PPARγ) protein concentration in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS), in association with neuroinflammatory markers and clinical severity. Based on subsequent reports on the possible involvement of other PPARs and PPARγ coactivator-1alpha (PGC-1α) in neuroinflammation in MS, we analyzed the protein levels of PPARα, PPARβ/δ, and PGC-1α in a subset of CSF samples from the same cohort of relapsing-remitting MS patients...
May 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28449155/mitochondrial-dysfunction-in-diabetic-cardiomyopathy-effect-of-mesenchymal-stem-cell-with-ppar-%C3%AE-agonist-or-exendin-4
#10
Mohamed Abd Elaziz Wassef, Ola M Tork, Laila A Rashed, Walaa Ibrahim, Heba Morsi, Dina Mohamed Mekawy Rabie
Therapy targeting mitochondria may provide novel ways to treat diabetes and its complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists and exendin-4; an analog of glucagon-like peptide-1 have shown cardioprotective properties in many cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy (DCM) in relation to mitochondrial dysfunction. This work included seven groups of adult male albino rats: the control group, the non-treated diabetic group, and the treated diabetic groups: one group was treated with MSCs only, the second with pioglitazone only, the third with MSCs and pioglitazone, the forth with exendin-4 only and the fifth with MSCs and exendin-4...
April 27, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28427149/interaction-between-ppar-%C3%AE-and-sorl1-gene-with-late-onset-alzheimer-s-disease-in-chinese-han-population
#11
Hui Zhang, Wei Zheng, Linlin Hua, Yutong Wang, Jinfeng Li, Hongying Bai, Shanshan Wang, Mingyao Du, Xuelian Ma, Chunyang Xu, Xiaodong Li, Bin Gong, Yunliang Wang
AIMS: To investigate the impact of sortilin-related receptor 1 gene 1 (SORL1) and peroxisome proliferator activated receptor gamma (PPAR G) gene single nucleotide polymorphisms (SNPs), gene- gene and gene- environment interactions and haplotype on late-onset Alzheimer's disease (LOAD) risk. METHODS: Hardy-Weinberg equilibrium (HWE), haplotype analysis and pairwise linkage disequilibrium (LD) analysis were investigated by using SNPStats (available online at http://bioinfo...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423012/15-hydroxyprostaglandin-dehydrogenase-15-pgdh-prevents-lipopolysaccharide-lps-induced-acute-liver-injury
#12
Lu Yao, Weina Chen, Kyoungsub Song, Chang Han, Chandrashekhar R Gandhi, Kyu Lim, Tong Wu
The NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S)-hydroxyl group of prostaglandin E2 (PGE2), converting the pro-inflammatory PGE2 to the anti-inflammatory 15-keto-PGE2 (an endogenous ligand for peroxisome proliferator-activated receptor-gamma [PPAR-γ]). To evaluate the significance of 15-PGDH/15-keto-PGE2 cascade in liver inflammation and tissue injury, we generated transgenic mice with targeted expression of 15-PGDH in the liver (15-PGDH Tg) and the animals were subjected to lipopolysaccharide (LPS)/Galactosamine (GalN)-induced acute liver inflammation and injury...
2017: PloS One
https://www.readbyqxmd.com/read/28405929/thermodynamics-in-cancers-opposing-interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway
#13
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
Cancer cells are the site of numerous metabolic and thermodynamic abnormalities. We focus this review on the interactions between the canonical WNT/beta-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) in cancers and their implications from an energetic and metabolic point of view. In numerous tissues, PPAR gamma activation induces inhibition of beta-catenin pathway, while the activation of the canonical WNT/beta-catenin pathway inactivates PPAR gamma. In most cancers but not all, PPAR gamma is downregulated while the WNT/beta-catenin pathway is upregulated...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28398573/skeletal-muscle-pgc1%C3%AE-1-nucleosome-position-and-260nt-dna-methylation-determine-exercise-response-and-prevent-ectopic-lipid-accumulation-in-men
#14
Sudip Bajpeyi, Jeffrey D Covington, Erin M Taylor, Laura K Stewart, Jose E Galgani, Tara M Henagan
Endurance exercise has been shown to improve lipid oxidation and increase mitochondrial content in skeletal muscle: two features that have shown dependence on increased expression of the PPAR gamma co-activator 1 alpha (PGC1α). It is also hypothesized that exercise related alterations in PGC1α expression occur through epigenetic regulation of nucleosome positioning in association with differential DNA methylation status within the PCG1α promoter. Here we show that when primary human myotubes from obese, type 2 diabetics are exposed to lipolytic stimulus (PFI) in vitro, nucleosome occupancy surrounding the -260 nucleotide (nt) region, a known regulatory DNA methylation site, is reduced...
April 10, 2017: Endocrinology
https://www.readbyqxmd.com/read/28397719/toll-like-receptor-4-signaling-pathway-in-the-protective-effect-of-pioglitazone-on-experimental-immunoglobulin-a-nephropathy
#15
Jia-Nan Zou, Jing Xiao, Sha-Sha Hu, Chen-Sheng Fu, Xiao-Li Zhang, Zhen-Xing Zhang, Yi-Jun Lu, Wei-Jun Chen, Zhi-Bin Ye
BACKGROUND: In vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-γ and TLR4 in IgAN has not been fully studied both in vitro and in vivo...
April 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28394398/genetic-variants-of-ppar-gamma-coactivator-1b-augment-nlrp3-mediated-inflammation-in-gouty-arthritis
#16
Wan-Chun Chang, Yeong-Jian Jan Wu, Wen-Hung Chung, Yun-Shien Lee, See-Wen Chin, Ting-Jui Chen, Yu-Sun Chang, Der-Yuan Chen, Shuen-Iu Hung
Objective.: Gout is characterized by recurrent attacks of arthritis with hyperuricaemia and urate crystal-induced inflammation. Although urate transporters are known as risk factors, the immunogenetics of gouty inflammation remains unclear. This study aimed to investigate the genetic association between immune/metabolism regulators and gout. Methods.: We enrolled 448 gout patients and 943 population controls from Taiwan; all were Han Chinese. We screened association between gout and 22 variants of candidate genes, including NLRP3 , caspase 1, peroxisome proliferator-activated receptor-γ, proliferator-activated receptor-γ coactivator 1α ( PPARGC1A ) and 1β ( PPARGC1B )...
March 1, 2017: Rheumatology
https://www.readbyqxmd.com/read/28391584/the-effect-of-ppar%C3%AE-agonist-on-sglt2-and-glucagon-expressions-in-alpha-cells-under-hyperglycemia
#17
M Kim, E J Lee, H M Shin, H S Jung, T K Kim, T N Kim, M J Kwon, S H Lee, B D Rhee, J H Park
BACKGROUND: Although sodium glucose cotransporter 2 (SGLT2) inhibitors have many beneficial effects for type 2 diabetes, including decreased cardiovascular death, recent reports that they increased glucagon through SGLT2 inhibition raised some concern. Troglitazone, Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, was reported to increase SGLT2 in renal proximal tubule cells, but its role on pancreatic alpha cells have not been reported. We investigated the effect of troglitazone on SGLT2 expression in alpha cells and subsequent glucagon regulation in hyperglycemia...
April 8, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28376311/contribution-of-ppar-gamma-in-modulation-of-acrolein-induced-inflammatory-signaling-in-gp91phox-knock-out-mice
#18
Zivar Yousefipour, Kasturi Ranganna, Mathew Joseph, Katarzyna Marek, Neha Chung, Alicia Nesbary, Mohammad A Newaz
Oxidative stress and inflammation are major contributors in acrolein toxicity. Peroxisome Proliferator Activated Receptor gamma (PPARγ) has antioxidant/anti-inflammatory effects. We investigated contribution of PPARγ ligand, GW1929, in attenuation of oxidative stress in acrolein-induced insult. Male gp91phox knockout (KO) mice were treated with acrolein (0.5 mg/kg; i.p.7 days) with/without GW1929 (GW, 0.5 mg/kg/day; orally-10 days). Liver was processed for further analysis. Acrolein significantly increased 8-Isoprostane and reduced PPARγ activity (P<0...
April 4, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28350954/integrating-drug-s-mode-of-action-into-quantitative-structure-activity-relationships-for-improved-prediction-of-drug-induced-liver-injury
#19
Leihong Wu, Zhichao Liu, Scott Auerbach, Ruili Huang, Minjun Chen, Kristin McEuen, Joshua Xu, Hong Fang, Weida Tong
Drug-induced liver injury (DILI) is complex in mechanism. Different drugs could undergo different mechanisms but result in the same DILI type, while the same drug could lead to different DILI types via different mechanisms. Therefore, predicting a drug's potential for DILI should take its underlying mechanisms into consideration. To achieve that, we constructed a novel approach by incorporating the drug's Mode of Action (MOA) into Quantitative Structure-Activity Relationship (QSAR) modeling. This MOA-DILI approach was examined using a data set of 333 drugs...
April 24, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28344789/a-ppar-gamma-agonist-protects-from-radiation-induced-intestinal-toxicity
#20
Monica Mangoni, Mariangela Sottili, Chiara Gerini, Isacco Desideri, Cinzia Bastida, Stefania Pallotta, Francesca Castiglione, Pierluigi Bonomo, Icro Meattini, Daniela Greto, Sabrina Cappelli, Lucia Di Brina, Mauro Loi, Giampaolo Biti, Lorenzo Livi
OBJECTIVE: Because of its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-neoplastic properties, the PPAR-γ agonist rosiglitazone is an interesting drug for investigating for use in the prevention and treatment of radiation-induced intestinal damage. We aimed to evaluate the radioprotective effect of rosiglitazone in a murine model of acute intestinal damage, assessing whether radioprotection is selective for normal tissues or also occurs in tumour cells. METHODS: Mice were total-body irradiated (12 Gy), with or without rosiglitazone (5 mg/kg/day)...
March 2017: United European Gastroenterology Journal
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