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https://www.readbyqxmd.com/read/29186286/obesity-induced-changes-in-hepatic-and-placental-clock-gene-networks-in-rat-pregnancy
#1
Rachael C Crew, Brendan J Waddell, Peter J Mark
Maternal obesity induces pregnancy complications and disturbs fetal development, but the specific mechanisms underlying these outcomes are unclear. Circadian rhythms are implicated in metabolic complications associated with obesity, and maternal metabolic adaptations to pregnancy. Accordingly, obesity-induced circadian dysfunction may drive adverse outcomes in obese pregnancy. This study investigated whether maternal obesity alters the rhythmic expression of clock genes and associated nuclear receptors across maternal, fetal and placental tissues...
November 25, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29162431/adenine-accelerated-the-diabetic-wound-healing-by-ppar-delta-and-angiogenic-regulation
#2
Jyh-Gang Leu, Ming-Hsing Chiang, Chao-Yi Chen, Jiun-Tsai Lin, Han-Min Chen, Yen-Lin Chen, Yao-Jen Liang
Wound healing is one of the major complications of diabetes, and problems with wound healing in diabetics often lead to amputation and even death. AMP-activated protein kinase (AMPK) is a protein involved in intracellular metabolism. Activated AMPK can reduce visceral fat and cholesterol synthesis and even inhibit hepatic gluconeogenesis. Activation of AMPK has been widely used in the treatment of type II diabetes. We applied an AMPK activator (Adenine) to human fibroblasts and to the wounds of streptozotocin-induced diabetic mice...
November 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29031719/macrophage-alternative-activation-confers-protection-against-lipotoxicity-induced-cell-death
#3
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/28962559/neuro-protective-effect-of-rutin-against-cisplatin-induced-neurotoxic-rat-model
#4
Mashal M Almutairi, Wael A Alanazi, Musaad A Alshammari, Moureq Rashed Alotaibi, Ali R Alhoshani, Salim Salah Al-Rejaie, Mohamed M Hafez, Othman A Al-Shabanah
BACKGROUND: Cisplatin is widely used chemotherapeutic agent for cancer treatment with limited uses due to its neurotoxic side effect. The aim of this study was to determine the potential preventive effects of rutin on the brain of cisplatin- neurotoxic rat model. METHODS: Forty rats were divided into four groups. Group-1 (control group) was intra-peritoneal (IP) injected with 2.5 ml/kg saline. Group-2 (rutin group) was orally administrated 30 mg/kg rutin dissolved in water for 14 days...
September 29, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28818518/seladelpar-mbx-8025-a-selective-ppar-%C3%AE-agonist-in-patients-with-primary-biliary-cholangitis-with-an-inadequate-response-to-ursodeoxycholic-acid-a-double-blind-randomised-placebo-controlled-phase-2-proof-of-concept-study
#5
David Jones, Pol F Boudes, Mark G Swain, Christopher L Bowlus, Michael R Galambos, Bruce R Bacon, Yvonne Doerffel, Norman Gitlin, Stuart C Gordon, Joseph A Odin, David Sheridan, Markus-Alexander Wörns, Virginia Clark, Linsey Corless, Heinz Hartmann, Mark E Jonas, Andreas E Kremer, George F Mells, Peter Buggisch, Bradley L Freilich, Cynthia Levy, John M Vierling, David E Bernstein, Marek Hartleb, Ewa Janczewska, Fedja Rochling, Hemant Shah, Mitchell L Shiffman, John H Smith, Yun-Jung Choi, Alexandra Steinberg, Monika Varga, Harinder Chera, Robert Martin, Charles A McWherter, Gideon M Hirschfield
BACKGROUND: Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid. METHODS: The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid...
October 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28555083/ppar-delta-modulates-membrane-cholesterol-and-cytokine-signaling-in-malignant-b-cells
#6
L Sun, Y Shi, G Wang, X Wang, S Zeng, S E Dunn, G D Fairn, Y-J Li, D E Spaner
A deeper understanding of the mechanisms that underlie aberrant signal transduction in B-cell cancers such as chronic lymphocytic leukemia (CLL) may reveal new treatment strategies. The lipid-activated nuclear receptor peroxisome proliferator-activated receptor delta (PPARδ) accounts for a number of properties of aggressive cancers and was found to enhance Janus kinase (JAK)-mediated phosphorylation of signal transducer and activator of transcription (STAT) proteins in B lymphoma cell lines and primary CLL cells...
May 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28320596/phillyrin-lowers-body-weight-in-obese-mice-via-the-modulation-of-ppar-beta-delta-angptl-4-pathway
#7
Hong-Bo Xiao, Guo-Guang Sui, Xiang-Yang Lu
OBJECTIVE: Previous investigations have shown that the peroxisome proliferator activated receptor beta/delta (PPAR<beta>/<delta>)-angiopoietin-like protein 4 (ANGPTL4) pathways may be a new pharmacologic target for treatment of obesity. The present study was conducted to test the effect of phillyrin, ‎a glucoside, on obesity in mice. METHOD: Fifty mice were randomly divided into 5 groups (n=10): control group (C57BL/6J mice), obese mice group, two groups of obese mice treated with phillyrin (15 or 45mg/kg/day), one group of obese mice treated with PPAR<beta>/<delta> agonist GW0742 (3mg/kg/day)...
March 17, 2017: Obesity Research & Clinical Practice
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/28050012/ppar-delta-promotes-survival-of-chronic-lymphocytic-leukemia-cells-in-energetically-unfavorable-conditions
#9
Y-J Li, L Sun, Y Shi, G Wang, X Wang, S E Dunn, C Iorio, R A Screaton, D E Spaner
Targeting the mechanisms that allow chronic lymphocytic leukemia (CLL) cells to survive in harsh cancer microenvironments should improve patient outcomes. The nuclear receptor peroxisome proliferator activated receptor delta (PPARδ) sustains other cancers, and in silico analysis showed higher PPARD expression in CLL cells than normal lymphocytes and other hematologic cancers. A direct association was found between PPARδ protein levels in CLL cells and clinical score. Transgenic expression of PPARδ increased the growth and survival of CD5(+) Daudi cells and primary CLL cells in stressful conditions including exhausted tissue culture media, low extracellular glucose, hypoxia and exposure to cytotoxic drugs...
September 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27818230/effect-of-ppar-%C3%AE-%C3%AE-agonist-gw0742-treatment-in-the-acute-phase-response-and-blood-brain-barrier-permeability-following-brain-injury
#10
Khouloud Chehaibi, Laura le Maire, Sarah Bradoni, Joan Carles Escola, Francisco Blanco-Vaca, Mohamed Naceur Slimane
The systemic response to ischemic stroke is associated with the hepatic acute phase response (APR) that modulates leukocytes recruitment to the injured brain. The inappropriate recruitment of leukocytes to the brain parenchyma can result in blood-brain barrier (BBB) breakdown. Emerging data suggest that peroxisome proliferator-activated receptor beta/delta (PPAR-β/δ) activation has a potential neuroprotective role in ischemic stroke. However, mechanisms of PPAR-β/δ mediated protection in ischemic insults remain unclear...
April 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27802237/improved-brain-insulin-igf-signaling-and%C3%A2-reduced-neuroinflammation-with%C3%A2-t3d-959-in-an-experimental-model%C3%A2-of%C3%A2-sporadic-alzheimer-s-disease
#11
Suzanne M de la Monte, Ming Tong, Irio Schiano, John Didsbury
BACKGROUND: Alzheimer's disease (AD) is associated with progressive impairments in brain insulin, insulin-like growth factor (IGF), and insulin receptor substrate (IRS) signaling through Akt pathways that regulate neuronal growth, survival, metabolism, and plasticity. The intracerebral streptozotocin (i.c. STZ) model replicates the full range of abnormalities in sporadic AD. T3D-959, an orally active PPAR-delta/gamma agonist remediates neurocognitive deficits and AD neuropathology in the i...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27702819/molecular-pathways-dietary-regulation-of-stemness-and-tumor-initiation-by-the-ppar-%C3%AE-pathway
#12
Semir Beyaz, Ömer H Yilmaz
Peroxisome proliferator-activated receptor delta (PPAR-δ) is a nuclear receptor transcription factor that regulates gene expression during development and disease states, such as cancer. However, the precise role of PPAR-δ during tumorigenesis is not well understood. Recent data suggest that PPAR-δ may have context-specific oncogenic and tumor-suppressive roles depending on the tissue, cell-type, or diet-induced physiology in question. For example, in the intestine, pro-obesity diets, such as a high-fat diet (HFD), are associated with increased colorectal cancer incidence...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27592051/ramipril-restores-ppar%C3%AE-%C3%AE-and-ppar%C3%AE-expressions-and-reduces-cardiac-nadph-oxidase-but-fails-to-restore-cardiac-function-and-accompanied-myosin-heavy-chain-ratio-shift-in-severe-anthracycline-induced-cardiomyopathy-in-rat
#13
Hana Cernecka, Gabriel Doka, Jasna Srankova, Lenka Pivackova, Eva Malikova, Kristina Galkova, Jan Kyselovic, Peter Krenek, Jan Klimas
We hypothesized that peroxisome proliferator-activated receptors (PPARs) might be involved in a complex protective action of ACE inhibitors (ACEi) in anthracyclines-induced cardiomyopathy. For purpose of study, we compared effects of ramipril on cardiac dysfunction, cardiac failure markers and PPAR isoforms in moderate and severe chronic daunorubicin-induced cardiomyopathy. Male Wistar rats were administered with a single intravenous injection of daunorubicin: 5mg/kg (moderate cardiomyopathy), or 15mg/kg (severe cardiomyopathy) or co-administered with daunorubicin and ramipril (1mg/kg/d, orally) or vehicle for 8 weeks...
November 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27525190/targeting-alzheimer-s-disease-neuro-metabolic-dysfunction-with-a-small-molecule-nuclear-receptor-agonist-t3d-959-reverses-disease-pathologies
#14
Ming Tong, Cesar Dominguez, John Didsbury, Suzanne M de la Monte
BACKGROUND: Alzheimer's disease (AD) could be regarded as a brain form of diabetes since insulin resistance and deficiency develop early and progress with severity of neurodegeneration. Preserving insulin's actions in the brain restores function and reduces neurodegeneration. T3D-959 is a dual nuclear receptor agonist currently in a Phase 2a trial in mild-to-moderate AD patients (ClinicalTrials.gov identifier NCT02560753). Herein, we show that T3D-959 improves motor function and reverses neurodegeneration in a sporadic model of AD...
June 2016: Journal of Alzheimer's Disease and Parkinsonism
https://www.readbyqxmd.com/read/27512842/association-between-peroxisome-proliferator-activated-receptor-alpha-delta-and-gamma-polymorphisms-and-risk-of-coronary-heart-disease-a-case-control-study-and-meta-analysis
#15
REVIEW
Yufeng Qian, Peiwei Li, Jinjie Zhang, Yu Shi, Kun Chen, Jun Yang, Yihua Wu, Xianhua Ye
OBJECTIVES: Risk of coronary heart disease (CHD) has been suggested to be associated with polymorphisms of peroxisome proliferator-activated receptors (PPARs), while the results were controversial. We aimed to systematically assess the association between PPAR polymorphisms and CHD risk. METHODS: A case-control study with 446 subjects was conducted to evaluate the association between CHD risk and C161T polymorphism, which was of our special interest as this polymorphism showed different effects on risks of CHD and acute coronary syndrome (ACS)...
August 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27511869/improved-methods-for-evaluating-pre-clinical-and-histological-effects-of-subcutaneous-fat-reduction-using-high-intensity-focused-ultrasound-in-a-porcine-model
#16
T-R Kwon, S Im, Y-J Jang, C T Oh, E J Choi, S J Jung, H Hong, Y S Choi, S Y Choi, Y S Kim, B J Kim
BACKGROUND: Non-invasive body sculpting procedures are becoming increasingly popular. High-intensity focused ultrasound (HIFU) treatment is a non-surgical fat reduction procedure that permanently destroys unwanted abdominal fat. Despite its increasing popularity, evaluation methods for the procedure have not yet been fully developed. AIMS: The objective of this study was to develop evaluation methods for HIFU for non-surgical, permanent fat reduction in the anterior abdomen using a porcine model...
May 2017: Skin Research and Technology
https://www.readbyqxmd.com/read/27424398/-ppars-mediate-the-regulation-of-energy-metabolism-by-long-chain-fatty-acids
#17
REVIEW
Yao Yan, Zong-Bao Wang, Chao-Ke Tang
PPAR-alpha expressed primarily in liver is essential for metabolic adaptation to starvation by inducing genes for beta-oxidation and ketogenesis to increase the utility of LCFAs and fibroblast growth factor 21. PPAR-delta induces genes for LCFA oxidation during fasting and endurance exercise in skeletal muscle. PPAR-delta also regulates glucose metabolism and mitochondrial biogenesis by inducing FOXO1 and PGC1-alpha. PPAR-gamma can induces the pathways to store LCFAs as triglycerides in adipocytes. Adiponectin, another important target of PPAR-gamma may maintain insulin sensitivity between adipocytes...
February 2016: Sheng Li Ke Xue Jin Zhan [Progress in Physiology]
https://www.readbyqxmd.com/read/27278004/pharmacological-activation-of-peroxisome-proliferator-activated-receptor-delta-increases-sphingomyelin-synthase-activity-in-thp-1-macrophage-derived-foam-cell
#18
Dongsheng Mou, Hua Yang, Changhua Qu, Juan Chen, Chaogui Zhang
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which mediate glucose and lipid homeostasis by regulating the expression of a large number of transcription factors. Sphingomyelin synthase (SMS) is a key enzyme in the synthesis of sphingomyelin (SM), and its expression and activity have been reported to be associated with atherosclerosis (AS). Although there have been many functional PPAR and SMS studies on atherosclerosis in recent years, few have investigated the correlation between the activation of PPARδ and the activity of SMS...
August 2016: Inflammation
https://www.readbyqxmd.com/read/27270614/ppar-delta-promotes-survival-of-breast-cancer-cells-in-harsh-metabolic-conditions
#19
X Wang, G Wang, Y Shi, L Sun, R Gorczynski, Y-J Li, Z Xu, D E Spaner
Expression of the nuclear receptor peroxisome proliferator activated receptor delta (PPARδ) in breast cancer cells is negatively associated with patient survival, but the underlying mechanisms are not clear. High PPARδ protein levels in rat breast adenocarcinomas were found to be associated with increased growth in soft agar and mice. Transgenic expression of PPARδ increased the ability of human breast cancer cell lines to migrate in vitro and form lung metastases in mice. PPARδ also conferred the ability to grow in exhausted tissue culture media and survive in low-glucose and other endoplasmic reticulum stress conditions such as hypoxia...
2016: Oncogenesis
https://www.readbyqxmd.com/read/27115677/peroxisome-proliferator-activated-receptors-in-cardiac%C3%A2-energy-metabolism-and-cardiovascular-disease
#20
REVIEW
Thekkuttuparambil Ananthanarayanan Ajith, Thankamani Gopinathan Jayakumar
Cardiomyocytes mainly depend on energy produced from the oxidation of fatty acids and mitochondrial oxidative phosphorylation. Shortage of energy or excessive fat accumulation can lead to cardiac disorders. High saturated fat intake and a sedentary life style have a major influence in the development of cardiovascular disease (CVD). Peroxisome proliferator-activated receptors (PPARs), one of the nuclear receptor super family members, play critical role in the metabolism of lipids by regulating their oxidation and storage...
July 2016: Clinical and Experimental Pharmacology & Physiology
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