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PPAR alpha

Terry D Hinds, Katherine A Burns, Peter A Hosick, Lucien McBeth, Andrea Nestor-Kalinoski, Heather A Drummond, Adbulhadi A AlAmodi, Michael W Hankins, John P Vanden Heuvel, David E Stec
Non-alcoholic fatty liver disease (NAFLD) is the most rapidly growing form of liver disease, and if left untreated can result in non-alcoholic steatohepatitis (NASH) ultimately resulting in liver cirrhosis and failure. Biliverdin reductase-A (BVRA) is a multi-functioning protein primarily responsible for the reduction of biliverdin to bilirubin. Also, BVRA can function as a kinase and transcription factor, regulating several cellular functions. We report here that liver BVRA protects against hepatic steatosis by inhibiting glycogen synthase kinase-3β (GSK3β) by enhancing serine 9 phosphorylation, which inhibits its activity...
October 10, 2016: Journal of Biological Chemistry
Ashraf S Gorgey, Zachary A Graham, William A Bauman, Christopher Cardozo, David R Gater
STUDY DESIGN: Longitudinal design. OBJECTIVES: The study determined the effects of two forms of exercise training on the abundance of two proteins, (glucose transporter-4 [GLUT-4], adenosine monophosphate kinase [AMPK]) involved in glucose utilization and the transcriptional coactivator that regulates the genes involved in energy metabolism and mitochondrial biogenesis (peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha [PGC-1α]), in muscles in men with chronic motor-complete spinal cord injury (SCI)...
October 13, 2016: Journal of Spinal Cord Medicine
Terry D Hinds, Samuel O Adeosun, Abdulhadi A Alamodi, David E Stec
Several large population studies have demonstrated a negative correlation between serum bilirubin levels and the development of obesity, hepatic steatosis, and cardiovascular disease. Despite the strong correlative data demonstrating the protective role of bilirubin, the mechanism by which bilirubin can protect against these pathologies remains unknown. Bilirubin has long been known as a powerful antioxidant and also has anti-inflammatory actions, each of which may contribute to the protection afforded by increased levels...
October 2016: Medical Hypotheses
Kalathookunnel Antony Antu, Mariam Philip Riya, Anupama Nair, Arvind Mishra, Arvind K Srivastava, Kozhiparambil Gopalan Raghu
ETHNOPHARMACOLOGICAL RELEVANCE: This plant has been utilized in Indian system of medicine for treatment of diabetes. This is clearly evident from the composition of Ayurvedic preparation for diabetes 'Nisakathakadi Kashayam' where this is one of the main ingredients of this preparation. AIM OF THE STUDY: The study aims in elucidating the molecular mechanisms underlying the insulin sensitizing effects of Symplocos cochinchinensis ethanol extract (SCE) using a high fructose and saturated fat (HFS) fed insulin resistant rat model...
September 26, 2016: Journal of Ethnopharmacology
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...
August 31, 2016: European Journal of Pharmacology
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
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)
Yu-Min Lin, Bu-Chin Yu, Wen-Tai Chiu, Hung-Yu Sun, Yu-Chieh Chien, Hui-Chen Su, Shu-Yang Yen, Hsin-Wen Lai, Chyi-Huey Bai, Kung-Chia Young, Chiung-Wen Tsao
Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase...
October 2016: International Journal of Oncology
Soundharrajan Ilavenil, Da Hye Kim, Srisesharam Srigopalram, Mariadhas Valan Arasu, Kyung Dong Lee, Jeong Chae Lee, Jong Suk Lee, Senthil Renganathan, Ki Choon Choi
Coumaric acid (CA) is a phenolic acid of the hydroxycinnamic acid family, and it has many biological functions such as anti-oxidant, anti-inflammatory, antidiabetic, anti-ulcer, anti-platelet, anti-cancer activities, etc. In the present study, we planned to analyse the potential molecular function of CA on skeletal muscle and preadipocytes differentiation using PCR and Western blot techniques. First, we analysed the impact of CA on C2C12 skeletal muscle differentiation. It revealed that CA treatment inhibited horse serum-induced skeletal muscle differentiation as evidenced by the decreased expression of early myogenic differentiation markers such as Myogenin and myoD via the AMP activated protein kinase- alpha AMPK-α mediated pathway...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
David Mizael Ortíz-Martinez, Catalina Rivas-Morales, Myriam Angelica de la Garza-Ramos, Maria Julia Verde-Star, Maria Adriana Nuñez-Gonzalez, Catalina Leos-Rivas
Diabetes mellitus is a public health problem worldwide. For this reason, ethanolic extract of Miconia sp. from Oaxaca, Mexico, was selected in search of an alternative against this disease. The effect of Miconia sp. on mRNA expression of PPARγ on cell line 3T3-L1, its effect on alpha amylase and alpha glucosidase, lipid accumulation during adipogenesis, and cell viability on VERO cells were evaluated. The mRNA levels of PPARγ increased on 1.393 ± 0.008 folds, lipid accumulation was increased by 29.55% with Miconia sp...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Agata Bielecka-Dabrowa, Agata Sakowicz, Małgorzata Misztal, Stephan von Haehling, Ali Ahmed, Tadeusz Pietrucha, Jacek Rysz, Maciej Banach
BACKGROUND/OBJECTIVES: To evaluate whether biomarkers reflecting pathophysiological pathways and selected single nucleotide polymorphisms differ between patients (pts) with heart failure (HF). METHODS: 110 pts with were involved, including HF pts with preserved ejection fraction (HFpEF, n=51) with hypertensive origin, HF pts with reduced ejection fraction (HFrEF) with ischemic aetiology (ICM) (n=32) and HFrEF with dilated cardiomyopathy (DCM) (n=27). We assessed selected HF biomarkers, echocardiographic examinations and functional polymorphisms selected from six candidate genes: CYP27B1, NOS3, IL-6, TGF beta, TNF alpha, and PPAR gamma...
October 15, 2016: International Journal of Cardiology
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]
S Afzal, M A Sattar, Edward J Johns, Mohammed H Abdulla, Safia Akhtar, Fayyaz Hashmi, Nor Azizan Abdullah
Adiponectin exerts vasodilatory effects. Irbesartan, an angiotensin receptor blocker, possesses partial peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist activity and increases circulating adiponectin. This study explored the effect of irbesartan alone and in combination with adiponectin on blood pressure, renal hemodynamic excretory function, and vasoactive responses to angiotensin II and adrenergic agonists in spontaneously hypertensive rat (SHR). Irbesartan was given orally (30 mg/kg/day) for 28 days and adiponectin intraperitoneally (2...
July 12, 2016: Journal of Physiology and Biochemistry
Luis E Gomez-Quiroz, Daekwan Seo, Yun-Han Lee, Mitsuteru Kitade, Timo Gaiser, Matthew Gillen, Seung-Bum Lee, Ma Concepcion Gutierrez-Ruiz, Elizabeth A Conner, Valentina M Factor, Snorri S Thorgeirsson, Jens U Marquardt
Recent studies confirmed a critical importance of c-Met signaling for liver regeneration by modulating redox balance. Here we used liver-specific conditional knockout mice (MetKO) and a nutritional model of hepatic steatosis to address the role of c-Met in cholesterol-mediated liver toxicity. Liver injury was assessed by histopathology and plasma enzymes levels. Global transcriptomic changes were examined by gene expression microarray, and key molecules involved in liver damage and lipid homeostasis were evaluated by Western blotting...
June 15, 2016: Toxicology
Omid Azimzadeh, Tamara Azizova, Juliane Merl-Pham, Vikram Subramanian, Mayur V Bakshi, Maria Moseeva, Olga Zubkova, Stefanie M Hauck, Nataša Anastasov, Michael J Atkinson, Soile Tapio
Epidemiological studies show a significant increase in ischemic heart disease (IHD) incidence associated with total external gamma-ray dose among Mayak plutonium enrichment plant workers. Our previous studies using mouse models suggest that persistent alteration of heart metabolism due to the inhibition of peroxisome proliferator-activated receptor (PPAR) alpha accompanies cardiac damage after high doses of ionising radiation. The aim of the present study was to elucidate the mechanism of radiation-induced IHD in humans...
July 6, 2016: Oncotarget
Kirk P Conrad
BACKGROUND: Important roles for G-protein-coupled receptors (GPCRs) have been identified in the maternal physiological adaptations to pregnancy and in the pathogenesis of preeclampsia. On this basis, GPCRs are potential therapeutic targets for preeclampsia. OBJECTIVES AND RATIONALE: In this review, vasopressin and apelin are initially considered in this context before the focus on the hormone relaxin and its cognate receptor, the relaxin/insulin-like family peptide receptor 1 (RXFP1)...
September 2016: Human Reproduction Update
Victor F Notta, Marcia B Aguila, Carlos A Mandarim-DE-Lacerda
BACKGROUND: Controlling obesity and other comorbidities in the population is a challenge in modern society. High-intensity interval training (HIIT) combines short periods of high-intensity exercise with long recovery periods or a low-intensity exercise. The aim was to assess the impact of HIIT in the context of diet-induced obesity in the animal model. METHODS: C57BL/6 mice were fed one of the two diets: standard chow (lean group [LE]) or a high-fat diet (obese group [OB])...
May 2016: Journal of Sports Medicine and Physical Fitness
Xudong Xu, Han Guo, Zuo Jing, Lichao Yang, Caixia Chen, Lu Peng, Xiaoqing Wang, Lu Yan, Rongting Ye, Xin Jin, Yiqing Wang
Inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Peroxisome proliferator-activated receptor-alpha (PPAR-α) and cannabinoid receptor 2 (CB2) crucially impact the modulation of inflammation. N-Oleoylethanolamine (OEA), a natural agonist of PPAR-α, can also upregulate the expression of CB2 in human umbilical vein endothelial cells (HUVECs) and further shows an anti- atherosclerotic effect. Our study was designed to determinate whether OEA could inhibit inflammation in HUVECs induced by tumour necrosis factor-α (TNF-α) and to identify the mechanism of OEA function...
June 7, 2016: Journal of Cardiovascular Pharmacology
Hidetoshi Yamada, Sayaka Kikuchi, Mayuka Hakozaki, Kaori Motodate, Nozomi Nagahora, Masamichi Hirose
PPARs regulate the expression of genes involved in lipid homeostasis. PPARs serve as molecular sensors of fatty acids, and their activation can act against obesity and metabolic syndromes. 8-Hydroxyeicosapentaenoic acid (8-HEPE) acts as a PPAR ligand and has higher activity than EPA. However, to date, the PPAR ligand activity of 8-HEPE has only been demonstrated in vitro. Here, we investigated its ligand activity in vivo by examining the effect of 8-HEPE treatment on high fat diet-induced obesity in mice. After the 4-week treatment period, the levels of plasma and hepatic triglycerides in the 8-HEPE-fed mice were significantly lower than those in the HFD-fed mice...
2016: Journal of Lipids
Kent Wehmeier, Luisa M Onstead-Haas, Norman C W Wong, Arshag D Mooradian, Michael J Haas
The vitamin D metabolite 24,25-dihydroxyvitamin D3 (24, 25[OH]2D3) was shown to induce nongenomic signaling pathways in resting zone chondrocytes and other cells involved in bone remodeling. Recently, our laboratory demonstrated that 24,25-[OH]2D3 but not 25-hydroxyvitamin D3, suppresses apolipoprotein A-I (apo A-I) gene expression and high-density lipoprotein (HDL) secretion in hepatocytes. Since 24,25-[OH]2D3 has low affinity for the vitamin D receptor (VDR) and little is known with regard to how 24,25-[OH]2D3 modulates nongenomic signaling in hepatocytes, we investigated the capacity of 24,25-[OH]2D3 to activate various signaling pathways relevant to apo A-I synthesis in HepG2 cells...
August 2016: Journal of Molecular Endocrinology
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