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ppar delta

L Sun, Y Shi, G Wang, X Wang, S Zeng, S E Dunn, G D Fairn, Y-J Li, D E Spaner
New treatment strategies may be uncovered with a deeper understanding of the mechanisms that underlie aberrant signal transduction in B cell cancers such as chronic lymphocytic leukemia (CLL). The lipid-activated nuclear receptor peroxisome proliferator-activated receptor delta (PPARδ) mediates a number of features 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
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
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
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...
January 31, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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
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
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
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
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 ( 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
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)
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
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]
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
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
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
Jingsong Shi, Song Jiang, Dandan Qiu, Weibo Le, Xiao Wang, Yinhui Lu, Zhihong Liu
OBJECTIVE: To investigate potential drugs for diabetic nephropathy (DN) using whole-genome expression profiles and the Connectivity Map (CMAP). METHODOLOGY: Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs) between late stage and early stage DN samples and the CMAP database were used to identify potential drugs for DN using bioinformatics methods...
2016: BioMed Research International
Gabriela Volpi-Lagreca, Susan K Duckett
Thirty-six Angus-cross steers (667 ± 34.4 kg initial BW, 24.5 mo) were used to assess the impact of short-term glycerin or high-fructose corn syrup administration via drinking water on meat quality and marbling deposition. Steers blocked by BW (3 blocks) were assigned randomly to 1 of 3 drinking water treatments: 1) control (CON), 2) 4.3% crude glycerin (GLYC), or 3) 4.3% high-fructose corn syrup (HFCS) for the final 25 d before slaughter. Average daily gain was lower ( = 0.01) and final live weight was lower ( < 0...
February 2016: Journal of Animal Science
Tapan Behl, Ishneet Kaur, Heena Goel, Anita Kotwani
Diabetic retinopathy, a common secondary complication of diabetes mellitus, involves extensive damage to the retinal microvasculature. Retina, being a susceptible target, is highly prone to hyperglycemia-induced molecular damages. PPAR receptor, chiefly gamma subtype, mediates numerous responses related to glucose metabolism and hence is utilized, through its agonism, for the restoration of normal insulin sensitivity and glucose homeostasis in the body. Although a number of synthetic PPAR-gamma receptor agonists have been developed and are being employed for treatment purposes, the role of its endogenous ligand in the prevention of diabetic retinopathy is poorly acknowledged...
May 15, 2016: Life Sciences
Kay-Dietrich Wagner, Ana Vukolic, Delphine Baudouy, Jean-François Michiels, Nicole Wagner
Peroxisome proliferator-activated receptors are nuclear receptors which function as ligand-activated transcription factors. Among them, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in the heart and thought to have cardioprotective functions due to its beneficial effects in metabolic syndrome. As we already showed that PPARβ/δ activation resulted in an enhanced cardiac angiogenesis and growth without impairment of heart function, we were interested to determine the effects of a specific activation of PPARβ/δ in the vasculature on cardiac performance under normal and in chronic ischemic heart disease conditions...
2016: PPAR Research
Mark Christian C Manio, Kazuo Inoue, Mina Fujitani, Shigenobu Matsumura, Tohru Fushiki
The combined activation of the cellular energy sensor AMP-activated protein kinase (AMPK) and the nuclear transcription factor peroxisome proliferator-activated receptor delta (PPARδ) has been demonstrated to improve endurance and muscle function by mimicking the effects of exercise training. However, their combined pharmacological activation with exercise training has not been explored. Balb/c mice were trained on a treadmill and administered both the AMPK activator AICAR and the PPARδ agonist GW0742 for 4 weeks...
March 2016: Physiological Reports
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