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https://www.readbyqxmd.com/read/28336257/a-novel-pyrazole-containing-indolizine-derivative-suppresses-nf-%C3%AE%C2%BAb-activation-and-protects-against-tnbs-induced-colitis-via-a-ppar-%C3%AE-dependent-pathway
#1
Yong Fu, Junting Ma, Xiafei Shi, Xiang-Yun Song, Yaping Yang, Shuke Xiao, Jiahuang Li, Wei-Jin Gu, Zhen Huang, Junfeng Zhang, Jiangning Chen
The nuclear factor-κB (NF-κB)-mediated activation of macrophages plays a key role in mucosal immune responses in Crohn's disease (CD). Moreover, increasing evidence shows that the activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) exerts satisfactory anti-inflammatory effects in experimental colitis models, mostly by suppressing NF-κB-mediated macrophage activation. Therefore, exploring therapeutic strategies to activate PPAR-γ and inhibit the NF-κB pathway in colonic macrophages holds great promise for the treatment of CD...
March 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28336108/vitamin-d-increases-ppar%C3%AE-expression-and-promotes-beneficial-effects-of-physical-activity-in-metabolic-syndrome
#2
Rastegar Hoseini, Arsalan Damirchi, Parvin Babaei
OBJECTIVES: Peroxisome proliferator-activated receptor (PPAR) and vitamin D signaling pathways regulate a multitude of genes involved in different physiological functions. The aim of the present study was to examine the effects of vitamin D supplementation and aerobic training on metabolic syndrome and PPARγ expression. METHODS: Forty female ovariectomized rats were divided into five groups of aerobic training with high (OVX + Exe + HD), moderate (OVX + Exe + MD), and low dose of vitamin D (OVX + Exe + LD), aerobic training receving vehicle (sesame oil; OVX + Exe + oil), and sham-operated control (sham) groups...
April 2017: Nutrition
https://www.readbyqxmd.com/read/28323032/metabolic-re-wiring-of-isogenic-breast-epithelial-cell-lines-following-epithelial-to-mesenchymal-transition
#3
Skarphedinn Halldorsson, Neha Rohatgi, Manuela Magnusdottir, Kumari Sonal Choudhary, Thorarinn Guðjónsson, Erik Knutsen, Anna Barkovskaya, Bylgja Hilmarsdottir, Maria Perander, Gunhild M Mælandsmo, Steinn Gudmundsson, Óttar Rolfsson
Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28315901/the-effect-of-sitagliptin-on-lipid-metabolism-of-fatty-liver-mice-and-related-mechanisms
#4
Bilin Xu, Tian Shen, Lin Chen, Juan Xia, Cuiping Zhang, Hongping Wang, Ming Yu, Tao Lei
BACKGROUND In clinics, patients with type 2 diabetes complicated with non-alcoholic fatty liver disease (NAFLD) have been shown to receive significant improvements in blood glucose levels, lipid levels, and liver function after sitagliptin treatment, although the mechanism of drug action remains poorly understood. This study investigated the possible mechanism of sitagliptin on lipid metabolism of NAFLD mice. MATERIAL AND METHODS Male C57/BL6 mice were induced for NAFLD via 16 weeks of a high-fat diet, and were treated with 15 mg/kg/day sitagliptin for 16 consecutive weeks...
March 19, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28302472/erk1-and-erk2-activation-modulates-diet-induced-obesity-in-mice
#5
Amira Sayed Khan, Selvakumar Subramaniam, Gado Dramane, Douadi Khelifi, Naim Akhtar Khan
Obesity is a worldwide problem, and dietary lipids play an important role in its pathogenesis. Recently, Erk1 knock-out (ERK1(-/-)) mice have been shown to exhibit low preference for dietary fatty acids. Hence, we maintained Erk1(-/-) mice on a high-fat diet (HFD) to assess the implication of this mitogen-activated protein (MAP) kinase in obesity. The Erk1(-/-) mice, fed the HFD, were more obese than wild-type (WT) animals, fed the same diet. Erk1(-/-) obese mice gained more fat and liver mass than WT obese animals...
March 13, 2017: Biochimie
https://www.readbyqxmd.com/read/28298541/rosa-mosqueta-oil-prevents-oxidative-stress-and-inflammation-through-the-upregulation-of-ppar-%C3%AE-and-nrf2-in-c57bl-6j-mice-fed-a-high-fat-diet
#6
Daniel González-Mañán, Amanda D'Espessailles, Camila G Dossi, Marcela San Martín, Rodrigo A Mancilla, Gladys S Tapia
Background: Rosa mosqueta (RM) oil is characterized by high concentrations of antioxidants and α-linolenic acid (ALA; 18:3n-3). We have previously demonstrated in male C57BL/6J mice that RM decreases hepatic steatosis, a condition strongly associated with oxidative stress and inflammation.Objective: We studied the molecular mechanisms that underlie the role of RM in preventing high-fat diet (HFD)-induced oxidative stress and inflammation.Methods: Male C57BL/6J mice aged 28 d and weighing 12-14 g were divided into the following groups and fed for 12 wk: control diet (CD; 10% fat, 20% protein, and 70% carbohydrates); CD + RM (1...
March 15, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28292877/the-effects-of-dual-ppar%C3%AE-%C3%AE-agonism-compared-with-ace-inhibition-in-the-btbrob-ob-mouse-model-of-diabetes-and-diabetic-nephropathy
#7
Anette Ericsson, Pernilla Tonelius, Mark Lal, Alan Sabirsh, Gerhard Böttcher, Lena William-Olsson, Maria Strömstedt, Camilla Johansson, Gina Hyberg, Sofia Tapani, Ann-Cathrine Jönsson-Rylander, Robert Unwin
The leptin-deficient BTBRob/ob mouse develops progressive albuminuria and morphological lesions similar to human diabetic nephropathy (DN), although whether glomerular hyperfiltration, a recognized feature of early DN that may contribute to renal injury, also occurs in this model is not known. Leptin replacement has been shown to reverse the signs of renal injury in this model, but in contrast, the expected renoprotection by angiotensin-converting enzyme (ACE) inhibition in BTBRob/ob mice seems to be limited...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28287878/association-of-peroxisome-proliferator-activated-receptor-delta-and-additional-gene-smoking-interaction-on-cardiovascular-disease
#8
Wenqi Yang, Shudan Mao, Baoze Qu, Fengxiang Zhang, Zhaolong Xu
AIMS: To investigate the impact of peroxisome proliferator-activator receptor delta (PPARD) gene polymorphism and additional gene-smoking interaction on cardiovascular disease (CVD) risk based on this Chinese population. METHODS: A total of 1048 subjects (617 males, 431 females) with a mean age of 52.9 ± 14.1 years old were selected, including 520 CVD patients and 528 normal control subjects. The logistic regression model was used to examine the association between three SNPs and CVD risk, odds ratio (OR), and 95% confident interval (95%CI) were calculated...
2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28279226/the-ppar-pan-agonist-bezafibrate-ameliorates-cardiomyopathy-in-a-mouse-model-of-barth-syndrome
#9
Yan Huang, Corey Powers, Victoria Moore, Caitlin Schafer, Mindong Ren, Colin K L Phoon, Jeanne F James, Alexander V Glukhov, Sabzali Javadov, Frédéric M Vaz, John L Jefferies, Arnold W Strauss, Zaza Khuchua
BACKGROUND: The PGC-1α/PPAR axis has been proposed as a potential therapeutic target for several metabolic disorders. The aim was to evaluate the efficacy of the pan-PPAR agonist, bezafibrate, in tafazzin knockdown mice (TazKD), a mouse model of Barth syndrome that exhibits age-dependent dilated cardiomyopathy with left ventricular (LV) dysfunction. RESULTS: The effect of bezafibrate on cardiac function was evaluated by echocardiography in TazKD mice with or without beta-adrenergic stress...
March 9, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28275212/long-non-coding-rna-profiling-in-a-non-alcoholic-fatty-liver-disease-rodent-model-new-insight-into-pathogenesis
#10
Yi Chen, Haixiu Huang, Chengfu Xu, Chaohui Yu, Youming Li
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases worldwide with an unclear mechanism. Long non-coding RNAs (lncRNAs) have recently emerged as important regulatory molecules. To better understand NAFLD pathogenesis, lncRNA and messenger RNA (mRNA) microarrays were conducted in an NAFLD rodent model. Potential target genes of significantly changed lncRNA were predicted using cis/trans-regulatory algorithms. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then performed to explore their function...
January 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28273909/protectin-dx-increases-survival-in-a-mouse-model-of-sepsis-by-ameliorating-inflammation-and-modulating-macrophage-phenotype
#11
Haifa Xia, Lin Chen, Hong Liu, Zhipeng Sun, Wen Yang, Yiyi Yang, Shunan Cui, Shengnan Li, Yaxin Wang, Limin Song, Amro Fayez Abdelgawad, You Shang, Shanglong Yao
Recently, a serial of studies have demonstrated that lipid mediators derived from Omega-3 fatty acid docosahexaenoic acid have pro-resolving or anti-inflammatory effects in many inflammatory diseases. Here, we sought to evaluate whether Protectin DX (PDX, an isomer of Protecin D1), a newly identified lipid mediator, could protect mice against sepsis and explore the underling mechanism. Animal model of sepsis was established by cecum ligation and puncture (CLP). We found that PDX increased overall survival rate within eight days and attenuated multiple organ injury in septic mice...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28271032/bezafibrate-ameliorates-diabetes-via-reduced-steatosis-and-improved-hepatic-insulin-sensitivity-in-diabetic-tallyho-mice
#12
Andras Franko, Susanne Neschen, Jan Rozman, Birgit Rathkolb, Michaela Aichler, Annette Feuchtinger, Laura Brachthäuser, Frauke Neff, Marketa Kovarova, Eckhard Wolf, Helmut Fuchs, Hans-Ulrich Häring, Andreas Peter, Martin Hrabě de Angelis
OBJECTIVE: Recently, we have shown that Bezafibrate (BEZ), the pan-PPAR (peroxisome proliferator-activated receptor) activator, ameliorated diabetes in insulin deficient streptozotocin treated diabetic mice. In order to study whether BEZ can also improve glucose metabolism in a mouse model for fatty liver and type 2 diabetes, the drug was applied to TallyHo mice. METHODS: TallyHo mice were divided into an early (ED) and late (LD) diabetes progression group and both groups were treated with 0...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28264426/the-combination-of-blueberry-juice-and-probiotics-ameliorate-non-alcoholic-steatohepatitis-nash-by-affecting-srebp-1c-pnpla-3-pathway-via-ppar-%C3%AE
#13
Tingting Ren, Juanjuan Zhu, Lili Zhu, Mingliang Cheng
Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured...
February 27, 2017: Nutrients
https://www.readbyqxmd.com/read/28258256/decreased-adiponectin-mediated-signaling-through-the-adipor2-pathway-is-associated-with-carotid-plaque-instability
#14
Karina Gasbarrino, Huaien Zheng, Anouar Hafiane, John P Veinot, Chi Lai, Stella S Daskalopoulou
BACKGROUND AND PURPOSE: Adiponectin, the most abundantly secreted anti-inflammatory adipokine, protects against all stages of atherosclerotic plaque formation by acting on its receptors, AdipoR1 (adiponectin receptor 1) and AdipoR2 (adiponectin receptor 2). Through binding of AdipoR1, adiponectin leads to the activation of the AMPK (adenosine monophosphate-activated protein kinase) pathway, whereas stimulation of PPAR-α (peroxisome proliferator-activated receptor-α) is attributed to the binding of AdipoR2...
March 3, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28257428/dietary-protein-induced-hepatic-igf-1-secretion-mediated-by-ppar%C3%AE-activation
#15
Xiaojuan Wan, Songbo Wang, Jingren Xu, Lu Zhuang, Kongping Xing, Mengyuan Zhang, Xiaotong Zhu, Lina Wang, Ping Gao, Qianyun Xi, Jiajie Sun, Yongliang Zhang, Tiejun Li, Gang Shu, Qingyan Jiang
Dietary protein or amino acid (AA) is a crucial nutritional factor to regulate hepatic insulin-like growth factor-1 (IGF-1) expression and secretion. However, the underlying intracellular mechanism by which dietary protein or AA induces IGF-1 expression remains unknown. We compared the IGF-1 gene expression and plasma IGF-1 level of pigs fed with normal crude protein (CP, 20%) and low-protein levels (LP, 14%). RNA sequencing (RNA-seq) was performed to detect transcript expression in the liver in response to dietary protein...
2017: PloS One
https://www.readbyqxmd.com/read/28219837/chronic-maternal-calcium-and-25-hydroxyvitamin-d-deficiency-in-wistar-rats-programs-abnormal-hepatic-gene-expression-leading-to-hepatic-steatosis-in-female-offspring
#16
Sona S Sharma, Nivedita M Jangale, Abhay M Harsulkar, Medha K Gokhale, Bimba N Joshi
Importance of calcium and vitamin D deficiency is well established in adult dyslipidemia. We hypothesized that maternal calcium and vitamin D deficiency could alter offspring's lipid metabolism. Our objective was to investigate the effect of maternal dietary calcium and vitamin D deficiency on lipid metabolism and liver function of the F1 generation offspring. intergenerational calcium-deficient (CaD) and vitamin D-deficient (VDD) models were developed by mating normal male rats with deficient females and continuing maternal-deficient diets through pregnancy and lactation...
February 8, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28219679/thiazolidinediones-abrogate-cervical-cancer-growth
#17
Beverly R Wuertz, Lindsay Darrah, Justin Wudel, Frank G Ondrey
Peroxisome proliferator-activated receptor gamma (PPAR γ) is activated by thiazolidinedione drugs (TZDs) and can promote anti-cancer properties. We used three TZDs (pioglitazone, rosiglitazone, and ciglitazone) to target cervical cancer cell lines and a nude mouse animal model. Each agent increased activation of PPAR γ, as judged by a luciferase reporter gene assay in three HPV-associated cell lines (CaSki, SiHa, and HeLa cells) while decreasing cellular proliferation in a dose-dependent manner. They also promoted Oil Red O accumulation in treated cell lines and upregulated the lipid differentiation marker adipsin...
February 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28218651/proteome-characteristics-of-non-alcoholic-steatohepatitis-liver-tissue-and-associated-hepatocellular-carcinomas
#18
Anna Kakehashi, Vasily E Stefanov, Naomi Ishii, Takahiro Okuno, Hideki Fujii, Kazuaki Kawai, Norifumi Kawada, Hideki Wanibuchi
To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV⁺ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207769/role-of-glycogen-synthase-kinase-3%C3%AE-and-ppar-%C3%AE-on-epithelial-to-mesenchymal-transition-in-dss-induced-colorectal-fibrosis
#19
Jacopo Di Gregorio, Roberta Sferra, Silvia Speca, Antonella Vetuschi, Caroline Dubuquoy, Pierre Desreumaux, Simona Pompili, Loredana Cristiano, Eugenio Gaudio, Vincenzo Flati, Giovanni Latella
BACKGROUND: Intestinal fibrosis is characterized by abnormal production and deposition of extracellular matrix (ECM) proteins by activated myofibroblasts. The main progenitor cells of activated myofibroblasts are the fibroblasts and the epithelial cells, the latter through the epithelial-mesenchymal transition (EMT). AIM: To evaluate the action of the new PPAR-γ modulator, GED-0507-34 Levo (GED) on the expression of EMT associated and regulatory proteins such as TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, and GSK-3β, in a mouse model of DSS-induced intestinal fibrosis...
2017: PloS One
https://www.readbyqxmd.com/read/28202347/in-silico-design-chemical-synthesis-and-toxicological-evaluation-of-1-3-thiazolidine-2-4-dione-derivatives-as-ppar%C3%AE-agonists
#20
Diana Alemán-González-Duhart, Feliciano Tamay-Cach, José Correa-Basurto, Itzia Irene Padilla-Martínez, Samuel Álvarez-Almazán, Jessica Elena Mendieta-Wejebe
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the metabolism of lipids and carbohydrates. The exogenous ligands of these receptors are thiazolidinediones (TZDs), which are used to treat type 2 diabetes mellitus (DM2). However, drugs from this group produce adverse effects such as hepatic steatosis. Hence, the aim of this work was to design a set of small molecules that can activate the γ isoform of PPARs while minimizing the adverse effects. The derivatives were designed containing the polar head of TZD and an aromatic body, serving simultaneously as the body and tail...
February 12, 2017: Regulatory Toxicology and Pharmacology: RTP
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