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Farsenoid X Receptor

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https://www.readbyqxmd.com/read/27880978/defining-the-relationship-between-farsenoid-x-receptor-hepatitis-b-virus-x-protein-and-hcc-it-s-complicated
#1
EDITORIAL
Lindsey Kennedy, Heather Francis
The relationship between hepatitis B virus X protein (HBx), farsenoid X receptor (FXR) and hepatocellular carcinoma (HCC) is a complicated one in that we have a viral protein interaction that can drive tumorigenesis or inhibit HCC depending upon transactivation of full-length or truncated HBx. In the current article the authors have elegantly described a system of HBx-FXR interaction that demonstrates inhibition of HCC tumor growth via activation of full-length HBx. The paper employs both in vivo and in vitro studies including using FXR knockout mice crossed with HBx induced mice...
November 23, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/26950211/hormesis-in-cholestatic-liver-disease-preconditioning-with-low-bile-acid-concentrations-protects-against-bile-acid-induced-toxicity
#2
Esther M Verhaag, Manon Buist-Homan, Martijn Koehorst, Albert K Groen, Han Moshage, Klaas Nico Faber
INTRODUCTION: Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis. AIM: To investigate the mechanisms that underlie the hormetic response that protect hepatocytes against experimental cholestatic conditions...
2016: PloS One
https://www.readbyqxmd.com/read/26378648/pharmacotherapy-for-nonalcoholic-fatty-liver-disease
#3
REVIEW
Samer Gawrieh, Naga Chalasani
Lifestyle modifications and optimization of the management of cardiometabolic comorbidities are currently the mainstay of treatment for patients with nonalcoholic fatty liver disease. Pharmacotherapy to halt or reverse hepatic histological injury and prevent the development of end-stage liver disease is specifically offered to patients with nonalcoholic steatohepatitis (NASH) and those with advanced fibrosis. In this review, the authors discuss the state of the art of various pharmacological agents for NASH...
August 2015: Seminars in Liver Disease
https://www.readbyqxmd.com/read/26052375/pathophysiological-mechanisms-involved-in-non-alcoholic-steatohepatitis-and-novel-potential-therapeutic-targets
#4
Fátima Higuera-de la Tijera, Alfredo I Servín-Caamaño
Non-alcoholic fatty liver disease (NAFLD) is a major health care problem and represents the hepatic expression of the metabolic syndrome. NAFLD is classified as non-alcoholic fatty liver (NAFL) or simple steatosis, and non-alcoholic steatohepatitis (NASH). NASH is characterized by the presence of steatosis and inflammation with or without fibrosis. The physiopathology of NAFL and NASH and their progression to cirrhosis involve several parallel and interrelated mechanisms, such as, insulin resistance (IR), lipotoxicity, inflammation, oxidative stress, and recently the gut-liver axis interaction has been described...
June 8, 2015: World Journal of Hepatology
https://www.readbyqxmd.com/read/25116592/clustering-nuclear-receptors-in-liver-regeneration-identifies-candidate-modulators-of-hepatocyte-proliferation-and-hepatocarcinoma
#5
Michele Vacca, Simona D'Amore, Giusi Graziano, Andria D'Orazio, Marica Cariello, Vittoria Massafra, Lorena Salvatore, Nicola Martelli, Stefania Murzilli, Giuseppe Lo Sasso, Renato Mariani-Costantini, Antonio Moschetta
BACKGROUND & AIMS: Liver regeneration (LR) is a valuable model for studying mechanisms modulating hepatocyte proliferation. Nuclear receptors (NRs) are key players in the control of cellular functions, being ideal modulators of hepatic proliferation and carcinogenesis. METHODS & RESULTS: We used a previously validated RT-qPCR platform to profile modifications in the expression of all 49 members of the NR superfamily in mouse liver during LR. Twenty-nine NR transcripts were significantly modified in their expression during LR, including fatty acid (peroxisome proliferator-activated receptors, PPARs) and oxysterol (liver X receptors, Lxrs) sensors, circadian masters RevErbα and RevErbβ, glucocorticoid receptor (Gr) and constitutive androxane receptor (Car)...
2014: PloS One
https://www.readbyqxmd.com/read/24670636/fxr-is-a-molecular-target-for-the-effects-of-vertical-sleeve-gastrectomy
#6
Karen K Ryan, Valentina Tremaroli, Christoffer Clemmensen, Petia Kovatcheva-Datchary, Andriy Myronovych, Rebekah Karns, Hilary E Wilson-Pérez, Darleen A Sandoval, Rohit Kohli, Fredrik Bäckhed, Randy J Seeley
Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at present the most effective therapy for the treatment of obesity, and are associated with considerable improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering the potential to reveal new targets for therapeutic intervention. Substantial changes in circulating total bile acids are known to occur after VSG. Moreover, bile acids are known to regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor, also known as NR1H4)...
May 8, 2014: Nature
https://www.readbyqxmd.com/read/24575869/probiotics-and-the-bsh-related-cholesterol-lowering-mechanism-a-jekyll-and-hyde-scenario
#7
REVIEW
Sy-Bing Choi, Lee-Ching Lew, Siok-Koon Yeo, Seema Nair Parvathy, Min-Tze Liong
Probiotic microorganisms have been documented over the past two decades to play a role in cholesterol-lowering properties via various clinical trials. Several mechanisms have also been proposed and the ability of these microorganisms to deconjugate bile via production of bile salt hydrolase (BSH) has been widely associated with their cholesterol lowering potentials in prevention of hypercholesterolemia. Deconjugated bile salts are more hydrophobic than their conjugated counterparts, thus are less reabsorbed through the intestines resulting in higher excretion into the feces...
2015: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/17414837/cholestasis-and-cholestatic-syndromes
#8
REVIEW
Jacqueline G O'Leary, Daniel S Pratt
PURPOSE OF REVIEW: This review focuses on the recent advances in cholestatic liver diseases. While there is an emphasis placed on translational and treatment-focused studies, basic science studies with the greatest impact on the field are also covered. RECENT FINDINGS: Highlights include new discoveries for the role of the farsenoid X receptor and sodium-dependent taurocholate cotransporting polypeptide; new insights into the pathogenesis of progressive familial intrahepatic cholestasis type 1, biliary atresia, intrahepatic cholestasis of pregnancy, and primary biliary cirrhosis; new information for assessing prognosis in biliary atresia and primary biliary cirrhosis; and important clinical trials in intrahepatic cholestasis of pregnancy, primary biliary cirrhosis and primary sclerosing cholangitis...
May 2007: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/17135343/the-hypolipidemic-agent-guggulsterone-regulates-the-expression-of-human-bile-salt-export-pump-dominance-of-transactivation-over-farsenoid-x-receptor-mediated-antagonism
#9
Ruitang Deng, Dongfang Yang, Amy Radke, Jian Yang, Bingfang Yan
Conversion of cholesterol to bile acids in the liver is initiated by the rate-limiting enzyme cholesterol 7alpha-hydroxylase (CYP7A1) and excretion of bile acids from the liver is mediated by the bile salt export pump (BSEP). The expression of CYP7A1 and BSEP is coordinately regulated by a negative feedback and positive feed-forward mechanism, respectively, through bile acid-mediated activation of farsenoid X receptor (FXR). It is well established that hypolipidemic agent guggulsterone is an FXR antagonist and down-regulates FXR target genes...
March 2007: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/16550034/cholestasis-and-cholestatic-syndromes
#10
REVIEW
Anna E Rutherford, Daniel S Pratt
PURPOSE OF REVIEW: This review highlights recent advances in understanding the regulation of bile acid transport in cholestasis and in the pathogenesis, outcomes, epidemiology, and treatment of a variety of cholestatic liver diseases and their associated complications. RECENT FINDINGS: Highlights include additional understanding of the role of the nuclear receptors farsenoid X receptor, pregnane X receptor, and constitutive androstane receptor in bile acid homeostasis, new understanding of the pathogenesis of primary biliary cirrhosis, familial intrahepatic cholestasis, biliary atresia, and primary sclerosing cholangitis, and clinical trials of therapies for intrahepatic cholestasis of pregnancy, primary biliary cirrhosis, and primary sclerosing cholangitis...
May 2006: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/16371446/oxysterol-22-r-hydroxycholesterol-induces-the-expression-of-the-bile-salt-export-pump-through-nuclear-receptor-farsenoid-x-receptor-but-not-liver-x-receptor
#11
Ruitang Deng, Dongfang Yang, Jian Yang, Bingfang Yan
Oxysterols are intermediates in the synthesis of bile acids and steroid hormones from cholesterol and function as ligands for liver X receptor (LXR). Bile salt export pump (BSEP) is responsible for canalicular secretion of bile acids and is tightly regulated by its substrates bile acids through nuclear receptor farnesoid X receptor (FXR). In a microarray study using human hepatocytes, BSEP was markedly induced not only by chenodeoxycholic acid (CDCA) but also by oxysterol 22(R)-hydroxycholesterol [22(R)-OHC]...
April 2006: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/14684380/dietary-cholesterol-stimulates-cyp7a1-in-rats-because-farnesoid-x-receptor-is-not-activated
#12
Guorong Xu, Lu-Xing Pan, Hai Li, Quan Shang, Akira Honda, Sarah Shefer, Jaya Bollineni, Yasushi Matsuzaki, G Stephen Tint, Gerald Salen
Cholesterol feeding upregulates CYP7A1 in rats but downregulates CYP7A1 in rabbits. To clarify the mechanism responsible for the upregulation of CYP7A1 in cholesterol-fed rats, the effects of dietary cholesterol (Ch) and cholic acid (CA) on the activation of the nuclear receptors, liver X-receptor (LXR-alpha) and farsenoid X-receptor (FXR), which positively and negatively regulate CYP7A1, were investigated in rats. Studies were carried out in four groups (n = 12/group) of male Sprague-Dawley rats fed regular chow (control), 2% Ch, 2% Ch + 1% CA, and 1% CA alone for 1 wk...
May 2004: American Journal of Physiology. Gastrointestinal and Liver Physiology
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