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https://www.readbyqxmd.com/read/28964868/the-neuroprotective-role-of-rosiglitazone-in-advanced-glycation-end-product-treated-human-neural-stem-cells-is-ppargamma-dependent
#1
Ming-Chang Chiang, Yi-Chuan Cheng, Christopher J Nicol, Chien-Hung Lin
Hyperglycemia is accompanied by an accelerated formation rate of advanced glycation end products (AGEs), which is associated with the pathogenesis of diabetic neuronal deficits. Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a family of ligand-activated nuclear receptors and its ligands are known to control many physiological, pathological and inflammatory pathways. Weinvestigated the hypothesis that the PPARγ agonist (rosiglitazone) would abrogate AGEs-mediated neurotoxic effects on human neural stem cells (hNSCs), by whichAGEs may play a role in diabetic-related neuronal impairment...
September 28, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28740126/evasion-of-immunosurveillance-by-genomic-alterations-of-ppar%C3%AE-rxr%C3%AE-in-bladder-cancer
#2
Manav Korpal, Xiaoling Puyang, Zhenhua Jeremy Wu, Roland Seiler, Craig Furman, Htoo Z Oo, Michael Seiler, Sean Irwin, Vanitha Subramanian, Jaya Julie Joshi, Chris K Wang, Victoria Rimkunas, Davide Tortora, Hua Yang, Namita Kumar, Galina Kuznetsov, Mark Matijevic, Jesse Chow, Pavan Kumar, Jian Zou, Jacob Feala, Laura Corson, Ryan Henry, Anand Selvaraj, Allison Davis, Kristjan Bloudoff, James Douglas, Bernhard Kiss, Morgan Roberts, Ladan Fazli, Peter C Black, Peter Fekkes, Peter G Smith, Markus Warmuth, Lihua Yu, Ming-Hong Hao, Nicholas Larsen, Mads Daugaard, Ping Zhu
Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. Although immunotherapies are approved for MIBC, the majority of patients fail to respond, suggesting existence of complementary immune evasion mechanisms. Here, we report that the PPARγ/RXRα pathway constitutes a tumor-intrinsic mechanism underlying immune evasion in MIBC. Recurrent mutations in RXRα at serine 427 (S427F/Y), through conformational activation of the PPARγ/RXRα heterodimer, and focal amplification/overexpression of PPARγ converge to modulate PPARγ/RXRα-dependent transcription programs...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28522250/ppargamma-agonists-rescue-increased-phosphorylation-of-fgf14-at-s226-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#3
Wei-Chun J Hsu, Norelle C Wildburger, Sigmund J Haidacher, Miroslav N Nenov, Oluwarotimi Folorunso, Aditya K Singh, Brent C Chesson, Whitney F Franklin, Ibdanelo Cortez, Rovshan G Sadygov, Kelly T Dineley, Jay S Rudra, Giulio Taglialatela, Cheryl F Lichti, Larry Denner, Fernanda Laezza
BACKGROUND: Cognitive impairment in humans with Alzheimer's disease (AD) and in animal models of Aβ-pathology can be ameliorated by treatments with the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ) agonists, such as rosiglitazone (RSG). Previously, we demonstrated that in the Tg2576 animal model of AD, RSG treatment rescued cognitive deficits and reduced aberrant activity of granule neurons in the dentate gyrus (DG), an area critical for memory formation...
September 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28521870/the-use-of-statins-alone-or-in-combination-with-pioglitazone-and-other-drugs-for-the-treatment-of-non-alcoholic-fatty-liver-disease-non-alcoholic-steatohepatitis-and-related-cardiovascular-risk-an-expert-panel-statement
#4
REVIEW
Vasilios G Athyros, Theodore K Alexandrides, Helen Bilianou, Evangelos Cholongitas, Michael Doumas, Emmanuel S Ganotakis, John Goudevenos, Moses S Elisaf, Georgios Germanidis, Olga Giouleme, Asterios Karagiannis, Charalambos Karvounis, Niki Katsiki, Vasilios Kotsis, Jannis Kountouras, Evangelos Liberopoulos, Christos Pitsavos, Stergios Polyzos, Loukianos S Rallidis, Dimitrios Richter, Apostolos G Tsapas, Alexandros D Tselepis, Konstantinos Tsioufis, Konstantinos Tziomalos, Themistoklis Tzotzas, Themistoklis G Vasiliadis, Charalambos Vlachopoulos, Dimitri P Mikhailidis, Christos Mantzoros
Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients...
June 2017: Metabolism: Clinical and Experimental
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
#5
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/28428362/hepatic-lipid-accumulation-cause-and-consequence-of-dysregulated-glucoregulatory-hormones
#6
REVIEW
Caroline E Geisler, Benjamin J Renquist
Fatty liver can be diet, endocrine, drug, virus or genetically induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator-activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic and ketogenic genes, promoting hyperglycemia, hyperlipidemia and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency and elevated sympathetic tone...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28406693/polychlorinated-biphenyl-153-in-lipid-medium-modulates-differentiation-of-human-adipocytes
#7
D Mullerova, M Pesta, J Dvorakova, M Cedikova, V Kulda, P Dvorak, V Bouchalová, M Kralickova, V Babuska, J Kuncova, J Langmajerova, L Muller
Emerging evidence indicates that polychlorinated biphenyls (PCBs) are involved in the development of diabetes mellitus in the obese. The purpose of this study was to determine mechanisms by which PCB 153 (2,2´,4,4´,5,5´-hexachlorobiphenyl) could influence diet-induced obesity and insulin resistance during adipogenesis. Lineage of h-ADMSCs was differentiated either as control (differentiation medium only), or with lipid vehicle modelling high fat nutrition (NuTRIflex) or lipid free vehicle (dimethylsulfoxide) for 28 days with or without PCB 153 daily co-exposure (in three concentrations 0...
April 12, 2017: Physiological Research
https://www.readbyqxmd.com/read/28396148/dok1-ppargamma-pathway-mediates-anti-tumor-ability-of-all-trans-retinoic-acid-in-breast-cancer-mcf-7%C3%A2-cells
#8
Xiaojun Ding, Wenjie Wang, Min Wang, Jiao Wu, Feng Yao
Previous studies have showed the anticancer effect of the all-trans retinoic acid (ATRA) in many tumors including breast cancer; however, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that ATRA treatment inhibited MCF-7 cell proliferation and promoted its apoptosis, along with an enhanced expression of docking protein 1 (DOK1). ATRA's effects on cell proliferation and apoptosis were prevented by DOK1 knockdown. In addition, the genetic silence of DOK1 can inhibit PPARγ expression and its activity...
April 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28293986/clear-cell-change-in-thyroid-carcinoma-a-clinicopathologic-and-molecular-study-with-identification-of-variable-genetic-anomalies
#9
Nicole A Cipriani, Shweta Agarwal, Dora Dias-Santagata, William C Faquin, Peter M Sadow
BACKGROUND: Clear-cell carcinoma of the thyroid has been regarded as a variant of follicular (FTC) or papillary (PTC) thyroid carcinoma. Twenty-one primary thyroid carcinomas with clear-cell features, diagnosed in 20 patients (12 female) were identified between 1992 and 2012 (0.5% of in-house thyroid carcinomas). METHODS: Hematoxylin and eosin slides were reviewed. SNaPshot multigene mutational analysis and a translocation panel were successfully performed on 15 of these cases...
June 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28270443/skeletal-muscle-pgc-1%C3%AE-signaling-is-sufficient-to-drive-an-endurance-exercise-phenotype-and-to-counteract-components-of-detraining-in-mice
#10
Samuel Lee, Teresa C Leone, Lisa Rogosa, John Rumsey, Julio Ayala, Paul M Coen, Robert H Fitts, Rick B Vega, Daniel P Kelly
Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response...
May 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27986616/thermogenesis-fatty-acid-synthesis-with-oxidation-and-inflammation-in-the-brown-adipose-tissue-of-ob-ob-mice
#11
Fabiane Ferreira Martins, Thereza Cristina Lonzetti Bargut, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Brown adipose tissue (BAT) is specialized in heat production, but its metabolism in ob/ob mice is still a matter of debate. We aimed to verify ob/ob mice BAT using C57Bl/6 male mice (as the wild-type, WT) and leptin-deficient ob/ob mice (on the C57Bl/6 background strain), at three months of age (n=10/group). At euthanasia, animals had their interscapular BAT weighed, and prepared for analysis (Western blot, and RT-qPCR). In comparison with the WT group, the ob/ob group showed reduced thermogenic signaling markers (gene expression of beta 3-adrenergic receptor, beta3-AR; PPARgamma coactivator 1 alpha, PGC1alpha, and uncoupling protein 1, UCP1)...
March 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/27876017/increased-wnt5a-in-squamous-cell-lung-carcinoma-inhibits-endothelial-cell-motility
#12
J Rapp, E Kiss, M Meggyes, E Szabo-Meleg, D Feller, G Smuk, T Laszlo, V Sarosi, T F Molnar, K Kvell, J E Pongracz
BACKGROUND: Angiogenesis is important both in normal tissue function and disease and represents a key target in lung cancer (LC) therapy. Unfortunately, the two main subtypes of non-small-cell lung cancers (NSCLC) namely, adenocarcinoma (AC) and squamous cell carcinoma (SCC) respond differently to anti-angiogenic e.g. anti-vascular endothelial growth factor (VEGF)-A treatment with life-threatening side effects, often pulmonary hemorrhage in SCC. The mechanisms behind such adverse reactions are still largely unknown, although peroxisome proliferator activator receptor (PPAR) gamma as well as Wnt-s have been named as molecular regulators of the process...
November 23, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27775420/the-role-of-ppargamma-in-cardiovascular-diseases
#13
REVIEW
M Kvandová, M Majzúnová, I Dovinová
The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear superfamily of ligand-activated transcription factors. PPARgamma acts as a nutrient sensor that regulates several homeostatic functions. Its disruption can lead to vascular pathologies, disorders of fatty acid/lipid metabolism and insulin resistance. PPARgamma can modulate several signaling pathways connected with blood pressure regulation. Firstly, it affects the insulin signaling pathway and endothelial dysfunction by modulation of expression and/or phosphorylation of signaling molecules through the PI3K/Akt/eNOS or MAPK/ET-1 pathways...
October 24, 2016: Physiological Research
https://www.readbyqxmd.com/read/27561621/brown-adipose-tissue-updates-in-cellular-and-molecular-biology
#14
REVIEW
Thereza Cristina Lonzetti Bargut, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Brown adipose tissue (BAT) is mainly composed of adipocytes, it is highly vascularized and innervated, and can be activated in adult humans. Brown adipocytes are responsible for performing non-shivering thermogenesis, which is exclusively mediated by uncoupling protein (UCP) -1 (a protein found in the inner mitochondrial membrane), the hallmark of BAT, responsible for the uncoupling of the proton leakage from the ATP production, therefore, generating heat (i.e. thermogenesis). Besides UCP1, other compounds are essential not only to thermogenesis, but also to the proliferation and differentiation of BAT, including peroxisome proliferator-activated receptor (PPAR) family, PPARgamma coactivator 1 (PGC1)-alpha, and PRD1-BF-1-RIZ1 homologous domain protein containing protein (PRDM) -16...
October 2016: Tissue & Cell
https://www.readbyqxmd.com/read/27435678/adipogenic-differentiation-of-thyroid-cancer-cells-through-the-pax8-ppar%C3%AE-fusion-protein-is-regulated-by-thyroid-transcription-factor-1-ttf-1
#15
Bin Xu, Michael O'Donnell, Jeffrey O'Donnell, Jingcheng Yu, Yanxiao Zhang, Maureen A Sartor, Ronald J Koenig
A subset of thyroid carcinomas contains a t(2;3)(q13;p25) chromosomal translocation that fuses paired box gene 8 (PAX8) with the peroxisome proliferator-activated receptor γ gene (PPARG), resulting in expression of a PAX8-PPARγ fusion protein, PPFP. We previously generated a transgenic mouse model of PPFP thyroid carcinoma and showed that feeding the PPARγ agonist pioglitazone greatly decreased the size of the primary tumor and prevented metastatic disease in vivo The antitumor effect correlates with the fact that pioglitazone turns PPFP into a strongly PPARγ-like molecule, resulting in trans-differentiation of the thyroid cancer cells into adipocyte-like cells that lose malignant character as they become more differentiated...
September 9, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27171144/perfluorooctanesulfonate-mediates-renal-tubular-cell-apoptosis-through-ppargamma-inactivation
#16
Li-Li Wen, Chien-Yu Lin, Hsiu-Chu Chou, Chih-Cheng Chang, Hau-Yin Lo, Shu-Hui Juan
Perfluorinated chemicals (PFCs) are ubiquitously distributed in the environments including stainless pan-coating, raincoat, fire extinguisher, and semiconductor products. The PPAR family has been shown to contribute to the toxic effects of PFCs in thymus, immune and excretory systems. Herein, we demonstrated that perfluorooctanesulfonate (PFOS) caused cell apoptosis through increasing ratio of Bcl-xS/xL, cytosolic cytochrome C, and caspase 3 activation in renal tubular cells (RTCs). In addition, PFOS increased transcription of inflammatory cytokines (i...
2016: PloS One
https://www.readbyqxmd.com/read/27157387/effect-of-high-glucose-concentration-on-human-preadipocytes-and-their-response-to-macrophage-conditioned-medium
#17
Vian Peshdary, AnneMarie Gagnon, Alexander Sorisky
OBJECTIVES: Adipose tissue expands via differentiation of preadipocytes into adipocytes (adipogenesis) and/or hypertrophy of existing adipocytes. A low adipogenic capacity promotes adipocyte hypertrophy, causing inflammatory macrophage accumulation and insulin resistance. Macrophage-conditioned medium (MacCM) inhibits adipogenesis and promotes adipocyte inflammation, but it is unknown whether these effects are altered by high glucose (HG) versus normal glucose (NG) concentrations. Our aim was to compare the effect of HG-MacCM versus NG-MacCM on human adipogenesis and adipocyte inflammation...
October 2016: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/27140638/preventing-diet-induced-obesity-in-mice-by-adipose-tissue-transformation-and-angiogenesis-using-targeted-nanoparticles
#18
Yuan Xue, Xiaoyang Xu, Xue-Qing Zhang, Omid C Farokhzad, Robert Langer
The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vasculature, angiogenesis offers a potential target for the treatment of obesity-associated disorders. Here we construct two peptide-functionalized nanoparticle (NP) platforms to deliver either Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) activator rosiglitazone (Rosi) or prostaglandin E2 analog (16,16-dimethyl PGE2) to adipose tissue vasculature...
May 17, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27040153/the-anti-hepatic-fibrosis-activity-of-ergosterol-depended-on-upregulation-of-ppargamma-in-hsc-t6-cells
#19
Chen-Jei Tai, Chen-Yen Choong, Yu-Chun Lin, Yeu-Ching Shi, Cheng-Jeng Tai
Advanced glycation endproducts (AGEs) were shown to play an important role in metabolic syndrome and were suggested to contribute to the development of hepatic fibrosis. Evidence indicates that AGEs resulted in hepatic fibrosis coupled to the activation of the receptor for AGEs (RAGE) in hepatic stellate cells (HSCs). NADPH oxidase is downstream of the RAGE signaling pathway, resulting in an increase in reactive oxygen species (ROS), alpha-smooth muscle actin (alpha-SMA), RAGE, and matrix metalloproteinase-9 (MMP-9)...
April 2016: Food & Function
https://www.readbyqxmd.com/read/26829067/adipose-tissue-infiltration-in-normal-weight-subjects-and-its-impact-on-metabolic-function
#20
Isabel Moreno-Indias, Wilfredo Oliva-Olivera, Antonio Omiste, Daniel Castellano-Castillo, Said Lhamyani, Antonio Camargo, Francisco J Tinahones
Discordant phenotypes, metabolically healthy obese and unhealthy normal-weight individuals, are always interesting to provide important insights into the mechanistic link between adipose tissue dysfunction and associated metabolic alterations. Macrophages can release factors that impair the proper activity of the adipose tissue. Thus, studying subcutaneous and visceral adipose tissues, we investigated for the first time the differences in monocyte/macrophage infiltration, inflammation, and adipogenesis of normal-weight subjects who differed in their degree of metabolic syndrome...
June 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
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