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Ppar gamma

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https://www.readbyqxmd.com/read/29143738/bladder-cancer-associated-mutations-in-rxra-activate-peroxisome-proliferator-activated-receptors-to-drive-urothelial-proliferation
#1
Angela M Halstead, Chiraag D Kapadia, Jennifer Bolzenius, Clarence E Chu, Andrew Schriefer, Lukas D Wartman, Gregory R Bowman, Vivek K Arora
RXRA regulates transcription as part of a heterodimer with 14 other nuclear receptors, including the peroxisome proliferator-activated receptors (PPARs). Analysis from the TCGA raised the possibility that hyperactive PPAR signaling, either due to PPAR gamma gene amplification or RXRA hot-spot mutation (S427F/Y) drives 20-25% of human bladder cancers. Here we characterize mutant RXRA, demonstrating it induces enhancer/promoter activity in the context of RXRA/PPAR heterodimers in human bladder cancer cells. Structure-function studies indicate that the RXRA substitution allosterically regulates the PPAR AF2 domain via an aromatic interaction with the terminal tyrosine found in PPARs...
November 16, 2017: ELife
https://www.readbyqxmd.com/read/29113135/nonalcoholic-fatty-liver-disease-is-exacerbated-in-high-fat-diet-fed-gnotobiotic-mice-by-colonization-with-the-gut-microbiota-from-patients-with-nonalcoholic-steatohepatitis
#2
Chien-Chao Chiu, Yung-Hao Ching, Yen-Peng Li, Ju-Yun Liu, Yen-Te Huang, Yi-Wen Huang, Sien-Sing Yang, Wen-Ching Huang, Hsiao-Li Chuang
Nonalcoholic fatty liver disease (NAFLD) is a serious liver disorder associated with the accumulation of fat and inflammation. The objective of this study was to determine the gut microbiota composition that might influence the progression of NAFLD. Germ-free mice were inoculated with feces from patients with nonalcoholic steatohepatitis (NASH) or from healthy persons (HL) and then fed a standard diet (STD) or high-fat diet (HFD). We found that the epididymal fat weight, hepatic steatosis, multifocal necrosis, and inflammatory cell infiltration significantly increased in the NASH-HFD group...
November 6, 2017: Nutrients
https://www.readbyqxmd.com/read/29100332/the-farnesoid-x-receptor-negatively-regulates-osteoclastogenesis-in-bone-remodeling-and-pathological-bone-loss
#3
Ting Zheng, Ju-Hee Kang, Jung-Sun Sim, Jung-Woo Kim, Jeong-Tae Koh, Chan Soo Shin, Hyungsik Lim, Mijung Yim
Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Since the role of FXR in osteoclast differentiation remains ill-defined, we investigated the biological function of FXR on osteoclastogenesis, using FXR-deficient mice. We demonstrated that FXR deficiency increases osteoclast formation in vitro and in vivo. First, FXR deficiency was found to accelerate osteoclast formation via down-regulation of c-Jun N-terminal kinase (JNK) 1/2 expression...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098441/communicative-reprogramming-non-curative-hepatocellular-carcinoma-with-low-dose-metronomic-chemotherapy-cox-2-inhibitor-and-ppar-gamma-agonist-a-phase-ii-trial
#4
I Walter, U Schulz, M Vogelhuber, K Wiedmann, E Endlicher, F Klebl, R Andreesen, W Herr, L Ghibelli, C Hackl, R Wiest, A Reichle
Systemic therapy for advanced hepatocellular carcinoma (HCC) is still challenging. A biomodulatory therapy approach targeting the communicative infrastructure of HCC, including metronomic low-dose chemotherapy with capecitabine, pioglitazone and rofecoxib, has been evaluated in patients with non-curative HCC. Altogether 38 patients were evaluable in this one-arm, multicenter phase II trial. The primary endpoint, median progression-free survival was 2.7 months (95% CI: 1.6-3.79) for all evaluable patients and 8...
November 2, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29083445/the-gene-diet-associations-in-postmenopausal-women-with-newly-diagnosed-dyslipidemia
#5
B Grygiel-Górniak, E Kaczmarek, M Mosor, J Przysławski, J Nowak
OBJECTIVES: The aim of this study was to determine the relationship between polymorphisms of peroxisome proliferator activated receptor - PPAR gamma-2 (Pro12Ala, C1431T) and beta 3-adrenergic receptor - ADRB3 (Trp64Arg) and dietary habits in a group of postmenopausal women who were not under hypolipidemic treatment. DESIGN: Genetic, nutritional and anthropometric parameters were measured in 213 dyslipidemic (LDL ≥115 mg/dL) and 58 normolipidemic (LDL<115) postmenopausal women...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/29075989/uric-acid-and-obesity-related-phenotypes-in-postmenopausal-women
#6
B Grygiel-Górniak, M Mosor, J Marcinkowska, J Przysławski, J Nowak
The aim of this study was to find the genetic, metabolic, and nutritional risk factors, which can be associated with uric acid (UA) level. The risk factors related to uricemia were assessed among 271 postmenopausal women without cardiometabolic disorders and hypolipidemic/hypoglycemic treatment selected from a cohort of 1423 obese postmenopausal women. The bioimpedance analysis and biochemical and genetic analyses were performed in two groups characterized by serum UA ≥ 4 mg/dL (238 μmol/L) and < 4 mg/dL...
October 26, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29049722/a-ppar-gamma-agonist-rosiglitazone-suppresses-fibrotic-response-in-human-pterygium-fibroblasts-by-modulating-the-p38-mapk-pathway
#7
Selikem Abla Nuwormegbe, Joon Hyung Sohn, Sun Woong Kim
Purpose: Fibroblast activation may play an important role in pterygium progression. Synthetic peroxisome proliferator-activated receptor γ (PPAR-γ) ligands have been shown to be effective antifibrotic agents against transforming growth factor β1 (TGF-β1) induced fibrosis in several tissues. We aimed to investigate the antifibrotic effects of the PPAR-γ ligand rosiglitazone in pterygium fibroblasts and the underlying mechanisms. Methods: Profibrotic activation was induced by TGF-β1 in primary cultured human pterygium fibroblasts and the effect of rosiglitazone treatment on α-smooth muscle actin (α-SMA), and extra cellular matrix proteins synthesis was detected by western blotting, real-time PCR, immunostaining, and flow cytometry...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29042402/ginsenoside-rg3-ameliorated-hfd-induced-hepatic-steatosis-through-downregulation-of-stat5-ppar%C3%AE
#8
Jin-Bong Lee, Sung-Jin Yoon, Sang-Hyun Lee, Moo-Seung Lee, Haiyoung Jung, Tae-Don Kim, Suk Ran Yoon, Inpyo Choi, Ik-Soo Kim, Su Wol Chung, Hee Gu Lee, Jeong-Ki Min, Young-Jun Park
Healthy expansion of adipose tissue maintains metabolic homeostasis by storing excess chemical energy in increased fat mass. The STAT5-PPAR gamma pathway reportedly regulates adipocyte differentiation, lipid metabolism and adipogenesis. Ginsenoside Rg3 is one of the diverse groups of steroidal saponins, the major active components of ginseng, which have demonstrated pharmacological properties. In this study, we evaluated the therapeutic effects of ginsenoside Rg3 under pathological conditions in vitro and in vivo We examined the effects of ginsenoside Rg3 on glucose level, insulin sensitivity and lipogenesis in high-fat diet-fed C57BL/6 mice...
December 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29031719/macrophage-alternative-activation-confers-protection-against-lipotoxicity-induced-cell-death
#9
Lingling Dai, Prerna Bhargava, Kristopher J Stanya, Ryan K Alexander, Yae-Huei Liou, David Jacobi, Nelson H Knudsen, Alexander Hyde, Matthew R Gangl, Sihao Liu, Chih-Hao Lee
OBJECTIVE: Alternative activation (M2) of adipose tissue resident macrophage (ATM) inhibits obesity-induced metabolic inflammation. The underlying mechanisms remain unclear. Recent studies have shown that dysregulated lipid homeostasis caused by increased lipolysis in white adipose tissue (WAT) in the obese state is a trigger of inflammatory responses. We investigated the role of M2 macrophages in lipotoxicity-induced inflammation. METHODS: We used microarray experiments to profile macrophage gene expression regulated by two M2 inducers, interleukin-4 (Il-4), and peroxisome proliferator-activated receptor delta/gamma (Pparδ/Pparγ) agonists...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031063/anticancer-properties-of-4-thiazolidinone-derivatives-depend-on-peroxisome-proliferator-activated-receptor-gamma-ppar%C3%AE
#10
Konrad A Szychowski, Marcin L Leja, Danylo V Kaminskyy, Anna P Kryshchyshyn, Urszula E Binduga, Oleh R Pinyazhko, Roman B Lesyk, Jakub Tobiasz, Jan Gmiński
Peroxisome proliferator-activated receptors (PPARs) play an important role in numerous chronic diseases such as diabetes, obesity, atherosclerosis and cancer, and PPAR modulators are among the approved drugs and drug-candidates for their treatment. The aim of this study was to elucidate the involvement of PPARs in the mechanism of cytotoxic and pro-apoptotic action of novel anticancer 4-thiazolidinone derivatives (Les-2194, Les-3377, Les-3640) and approved 4-thiazolidinones (Rosiglitazone, Pioglitazone) towards the human squamous carcinoma (SCC-15) cell line...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29025280/effects-of-prenatal-ppar-%C3%AE-agonist-rosiglitazone-exposure-on-rat-hippocampus-development-in-a-time-dependent-manner-a-stereological-and-histopathological-study
#11
D Sağır, B Eren, B D Yılmaz, Z Eren, O N Keleş, A B Gökçe
Rosiglitazone is in the thiazolidinedione class of drugs used in the treatment of type 2 diabetes mellitus. It works as an insulin sensitizer by binding to the peroxisome proliferator-activated receptor gamma. We investigated the effects of prenatally administered rosiglitazone on pyramidal cell numbers and morphologies in the hippocampus at postnatal period using histochemical and stereological techniques, congenital morphological properties and the number of offspring in rats. Eighteen female rats were grouped into control (C), low-dose rosiglitazone (LDR) and high-dose rosiglitazone (HDR)...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29020601/pioglitazone-a-ppar%C3%AE-agonist-reduces-nicotine-craving-in-humans-with-marginal-effects-on-abuse-potential
#12
Jermaine D Jones, Sandra D Comer, Verena E Metz, Jeanne M Manubay, Shanthi Mogali, Roberto Ciccocioppo, Suky Martinez, Mudassir Mumtaz, Adam Bisaga
Possibly through their actions upon glia, peroxisome proliferator-activated receptor agonists (PPAR) have been shown to alter the abuse potential of addictive drugs in several preclinical models. The current study extends this research into the human laboratory as the first clinical study into the effects of the PPAR gamma agonist, pioglitazone, on the abuse potential of nicotine. Heavy smokers were recruited for this 3-week study. Upon admission, participants were randomized to either active (45mg, n=14) or placebo (0mg, n=13) PIO maintenance conditions for the duration of the study...
October 8, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29018784/peroxisome-proliferator-activated-receptor-gamma-inhibits-the-activation-of-stat3-in-cerulein-stimulated-pancreatic-acinar-cells
#13
Kyung Don Ju, Joo Weon Lim, Hyeyoung Kim
Cerulein-induced pancreatitis is similar to human edematous pancreatitis, characterized by the dysregulation of digestive enzyme production, edema formation, and an infiltration of inflammatory cells into the pancreas. We previously showed that the Janus kinase 2 (JAK2)/STAT3 pathway mediates inflammatory signaling in cerulein-stimulated pancreatic acinar cells. PPAR-γ has been implicated in the regulation of inflammatory responses in several cells. In the present study, we investigated the role of PPAR-γ in cerulein-induced activation of JAK2/STAT3 in pancreatic acinar cells...
September 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28972081/unique-interactome-network-signatures-for-ppar-gamma-nbsp-modulation-by-functional-selective-ligands
#14
Vinh Lam, Jie Zheng, Patrick Robert Griffin
The nuclear receptor PPARg regulates adipogenesis and plays a central role in lipid and glucose homeostasis, and is the molecular target of the glitazones (TZDs), therapeutics used to treat insulin resistance and type-2 diabetes (T2D).  While the TZDs, which are PPARg agonists, demonstrated robust clinical efficacy in T2D, their use has been hampered by an array of untoward side effects.  Paradoxically, partial agonists (e.g., MRL24), antagonists (e.g., SR1664), and inverse agonists (e.g., SR10171 and SR2595), possess similar insulin-sensitizing efficacy as the TZDs in obese diabetic mice...
September 29, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28949260/the-effects-of-coenzyme-q10-supplementation-on-gene-expression-related-to-insulin-lipid-and-inflammation-in-patients-with-polycystic-ovary-syndrome
#15
Elham Rahmani, Mehri Jamilian, Mansooreh Samimi, Maryam Zarezade Mehrizi, Esmat Aghadavod, Elmira Akbari, Omid Reza Tamtaji, Zatollah Asemi
OBJECTIVE: This research was conducted to assess the effects of coenzyme Q10 (CoQ10) intake on gene expression related to insulin, lipid and inflammation in subjects with polycystic ovary syndrome (PCOS). METHODS: This randomized double-blind, placebo-controlled trial was conducted on 40 subjects diagnosed with PCOS. Subjects were randomly allocated into two groups to intake either 100 mg CoQ10 (n = 20) or placebo (n = 20) per day for 12 weeks. Gene expression related to insulin, lipid and inflammation were quantified in blood samples of PCOS women with RT-PCR method...
September 26, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28942553/clinacanthus-nutans-mitigates-neuronal-apoptosis-and-ischemic-brain-damage-through-augmenting-the-c-ebp%C3%AE-driven-ppar-%C3%AE-transcription
#16
Jui-Sheng Wu, Mei-Han Kao, Hsin-Da Tsai, Wai-Mui Cheung, Jin-Jer Chen, Wei-Yi Ong, Grace Y Sun, Teng-Nan Lin
Clinacanthus nutans Lindau (C. nutans) is a traditional herbal medicine widely used in Asian countries for treating a number of remedies including snake and insect bites, skin rashes, viral infections, and cancer. However, the underlying molecular mechanisms for its action and whether C. nutans can offer protection on stroke damage in brain remain largely unknown. In the present study, we demonstrated protective effects of C. nutans extract to ameliorate neuronal apoptotic death in the oxygen-glucose deprivation model and to reduce infarction and mitigate functional deficits in the middle cerebral artery occlusion model, either administered before or after hypoxic/ischemic insult...
September 23, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28923856/genomic-activation-of-pparg-reveals-a-candidate-therapeutic-axis-in-bladder-cancer
#17
Jonathan T Goldstein, Ashton C Berger, Juliann Shih, Fujiko F Duke, Laura Furst, David J Kwiatkowski, Andrew D Cherniack, Matthew Meyerson, Craig A Strathdee
The PPARG gene encoding the nuclear receptor PPAR-gamma is activated in bladder cancer, either directly by gene amplification or mutation, or indirectly by mutation of the RXRA gene which encodes the heterodimeric partner of PPAR-gamma. Here we show that activating alterations of PPARG or RXRA lead to a specific gene expression signature in bladder cancers. Reducing PPARG activity, whether by pharmacologic inhibition or genetic ablation, inhibited proliferation of PPARG-activated bladder cancer cells. Our results offer a preclinical proof of concept for PPARG as a candidate therapeutic target in bladder cancer...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28922099/the-effects-of-probiotic-supplementation-on-gene-expression-related-to-inflammation-insulin-and-lipids-in-patients-with-multiple-sclerosis-a-randomized-double-blind-placebo-controlled-trial
#18
Omid Reza Tamtaji, Ebrahim Kouchaki, Mahmoud Salami, Esmat Aghadavod, Elmira Akbari, Maryam Tajabadi-Ebrahimi, Zatollah Asemi
BACKGROUND: Limited data are available assessing the effects of probiotic supplementation on gene expression related to inflammation, insulin, and lipids in patients with multiple sclerosis (MS). OBJECTIVES: The current study was conducted to assess the effects of probiotic supplementation on gene expression related to inflammation, insulin, and lipids in patients with MS. METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed among 40 patients with MS...
September 18, 2017: Journal of the American College of Nutrition
https://www.readbyqxmd.com/read/28916975/flaxseed-oil-supplementation-improve-gene-expression-levels-of-ppar-%C3%AE-lp-a-il-1-and-tnf-%C3%AE-in-type-2-diabetic-patients-with-coronary-heart-disease
#19
Ali Akbar Hashemzadeh, Nikoo Nasoohi, Fariba Raygan, Esmat Aghadavod, Elmira Akbari, Mohsen Taghizadeh, Mohammad Reza Memarzadeh, Zatollah Asemi
This study was carried out to determine the effects of flaxseed oil administration on gene expression levels related to insulin, lipid and inflammation in overweight diabetic patients with coronary heart disease (CHD). This randomized double-blind, placebo-controlled trial was conducted among 60 diabetic patients with CHD. Subjects were randomly allocated into two groups to intake either 1000 mg n-3 fatty acid from flaxseed oil containing 400 mg α-Linolenic acid [ALA (18:3n-3)] (n = 30) or placebo (n = 30) twice a day for 12 weeks...
November 2017: Lipids
https://www.readbyqxmd.com/read/28916286/toxicology-studies-of-primycin-sulphate-using-a-three-dimensional-3d-in-vitro-human-liver-aggregate-model
#20
Ágota Pénzes, Elhusseiny Mohamed Mahmud Abdelwahab, Judit Rapp, Zsanett A Péteri, Judit Bovári-Biri, Csaba Fekete, György Miskei, Krisztián Kvell, Judit E Pongrácz
Primycin-sulphate is a highly effective compound against Gram (G) positive bacteria. It has a potentially synergistic effect with vancomycin and statins which makes primycin-sulphate a potentially very effective preparation. Primycin-sulphate is currently used exclusively in topical preparations. In vitro animal hepatocyte and neuromuscular junction studies (in mice, rats, snakes, frogs) as well as in in vitro human red blood cell experiments were used to test toxicity. During these studies, the use of primycin-sulphate resulted in reduced cellular membrane integrity and modified ion channel activity...
November 5, 2017: Toxicology Letters
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