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https://www.readbyqxmd.com/read/29119003/novel-associations-of-bile-acid-diarrhoea-with-fatty-liver-disease-and-gallstones-a-cohort-retrospective-analysis
#1
Richard N Appleby, Jonathan D Nolan, Ian M Johnston, Sanjeev S Pattni, Jessica Fox, Julian Rf Walters
Background: Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea with a population prevalence of primary BAD around 1%. Previous studies have identified associations with low levels of the ileal hormone fibroblast growth factor 19 (FGF19), obesity and hypertriglyceridaemia. The aim of this study was to identify further associations of BAD. Methods: A cohort of patients with chronic diarrhoea who underwent (75)selenohomocholic acid taurate (SeHCAT) testing for BAD was further analysed retrospectively...
2017: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/29096734/endocrine-adiponectin-fgf15-19-axis-in-ethanol-induced-inflammation-and-alcoholic-liver-injury
#2
Min You, Zhou Zhou, Michael Daniels, Alvin Jogasuria
Alcoholic liver disease (ALD) is the most prevalent form of liver diseases, encompassing a spectrum of progressive pathological changes from steatosis to steatohepatitis to fibrosis/cirrhosis and hepatocellular carcinoma. Alcoholic steatosis/steatohepatitis is the initial stage of ALD and a major risk factor for advanced liver injuries. Adiponectin is a hormone secreted from adipocytes. Fibroblast growth factor (FGF) 15 (human homolog, FGF19) is an ileum-derived hormone. Adipocyte-derived adiponectin and gut-derived FGF15/19 regulate each other, share common signaling cascades and exert similar beneficial functions...
November 2, 2017: Gene Expression
https://www.readbyqxmd.com/read/29080340/bile-acids-in-cholestasis-and-its-treatment
#3
Juan Pablo Arab, Daniel Cabrera, Marco Arrese
Bile acids (BA) are key molecules in generating bile flow, which is an essential function of the liver. In the last decades there have been great advances in the understanding of the role of a number of specific transport proteins present at the sinusoidal and canalicular membrane domains of hepatocytes and cholangiocytes in generating and maintaining bile flow. Also, a clearer understanding on how BA regulate their own synthesis and the expression and/or function of transporters has been reached. This new knowledge has helped to better delineate the pathophysiology of cholestasis and the adaptive responses of hepatocytes to cholestatic liver injury as well as of the mechanisms of injury of biliary epithelia...
October 28, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/29076506/obesity-pharmacological-actions-of-fgf19-and-fgf21-revealed
#4
Alan Morris
No abstract text is available yet for this article.
December 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28988823/fgf19-fgf21-and-an-fgfr1-%C3%AE-klotho-activating-antibody-act-on-the-nervous-system-to-regulate-body-weight-and-glycemia
#5
Tian Lan, Donald A Morgan, Kamal Rahmouni, Junichiro Sonoda, Xiaorong Fu, Shawn C Burgess, William L Holland, Steven A Kliewer, David J Mangelsdorf
Despite the different physiologic functions of FGF19 and FGF21 as hormonal regulators of fed and fasted metabolism, their pharmacologic administration causes similar increases in energy expenditure, weight loss, and enhanced insulin sensitivity in obese animals. Here, in genetic loss-of-function studies of the shared co-receptor β-Klotho, we show that these pharmacologic effects are mediated through a common, tissue-specific pathway. Surprisingly, FGF19 and FGF21 actions in liver and adipose tissue are not required for their longer-term weight loss and glycemic effects...
November 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28983785/implications-of-fgf19-on-sorafenib-mediated-nitric-oxide-production-in-hepatocellular-carcinoma-cells-a-short-report
#6
Lixia Gao, Chloe Shay, Fenglin Lv, Xuli Wang, Yong Teng
BACKGROUND: Hepatocellular carcinoma (HCC), a primary neoplasm derived from hepatocytes, is the second leading cause of cancer mortality worldwide. Previous work has shown that fibroblast growth factor 19 (FGF19), an oncogenic driver, acts as a negative regulator of the therapeutic efficacy of the tyrosine kinase inhibitor sorafenib in HCC cells. The FGF19-mediated mechanism affecting sorafenib treatment, however, still remains to be resolved. Here, we hypothesize that the FGF19-FGFR4 axis may affect the effectiveness of sorafenib in the treatment of HCC...
October 5, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28981086/engineered-fibroblast-growth-factor-19-protects-from-acetaminophen-induced-liver-injury-and-stimulates-aged-liver-regeneration-in-mice
#7
Gloria Alvarez-Sola, Iker Uriarte, Maria U Latasa, Maddalen Jimenez, Marina Barcena-Varela, Eva Santamaría, Raquel Urtasun, Carlos Rodriguez-Ortigosa, Jesús Prieto, Fernando J Corrales, Anna Baulies, Carmen García-Ruiz, Jose C Fernandez-Checa, Pedro Berraondo, Maite G Fernandez-Barrena, Carmen Berasain, Matías A Avila
The liver displays a remarkable regenerative capacity triggered upon tissue injury or resection. However, liver regeneration can be overwhelmed by excessive parenchymal destruction or diminished by pre-existing conditions hampering repair. Fibroblast growth factor 19 (FGF19, rodent FGF15) is an enterokine that regulates liver bile acid and lipid metabolism, and stimulates hepatocellular protein synthesis and proliferation. FGF19/15 is also important for liver regeneration after partial hepatectomy (PH). Therefore recombinant FGF19 would be an ideal molecule to stimulate liver regeneration, but its applicability may be curtailed by its short half-life...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28972963/a-phase-1-study-of-arq-087-an-oral-pan-fgfr-inhibitor-in-patients-with-advanced-solid-tumours
#8
K P Papadopoulos, B F El-Rayes, A W Tolcher, A Patnaik, D W Rasco, R D Harvey, P M LoRusso, J C Sachdev, G Abbadessa, R E Savage, T Hall, B Schwartz, Y Wang, J Kazakin, W L Shaib
BACKGROUND: ARQ 087 is an orally administered pan-FGFR inhibitor with multi-kinase activity. This Phase 1 study evaluated safety, pharmacokinetics, and pharmacodynamics of ARQ 087 and defined the recommended Phase 2 dose (RP2D). METHODS: Patients with advanced solid tumours received ARQ 087 administered initially at 25 mg every other day and dose-escalated from 25 to 425 mg daily (QD) continuous dosing. FGF19, 21, 23, and serum phosphate were assessed as potential biomarkers of target engagement...
October 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28965883/nuclear-receptor-fxr-bile-acids-and-liver-damage-introducing-the-progressive-familial-intrahepatic-cholestasis-with-fxr-mutations
#9
REVIEW
Marica Cariello, Elena Piccinin, Oihane Garcia-Irigoyen, Carlo Sabbà, Antonio Moschetta
The nuclear receptor farnesoid X receptor (FXR) is the master regulator of bile acids (BAs) homeostasis since it transcriptionally drives modulation of BA synthesis, influx, efflux, and detoxification along the enterohepatic axis. Due to its crucial role, FXR alterations are involved in the progression of a plethora of BAs associated inflammatory disorders in the liver and in the gut. The involvement of the FXR pathway in cholestasis development and management has been elucidated so far with a direct role of FXR activating therapy in this condition...
September 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28951455/fgf19-protects-hepatocellular-carcinoma-cells-against-endoplasmic-reticulum-stress-via-activation-of-fgfr4-gsk3%C3%AE-nrf2-signaling
#10
Yong Teng, Huakan Zhao, Lixia Gao, Wenfa Zhang, Austin Y Shull, Chloe Shay
The tumor microenvironment induces endoplasmic reticulum (ER) stress in tumor cells, an event that can promote progression, but it is unknown how tumor cells adapt to this stress. In this study, we show that the fibroblast growth factor FGF19, a gene frequently amplified in hepatocellular carcinoma (HCC), facilitates a survival response to ER stress. Levels of FGF19 expression were increased in stressed HCC cells in culture and in a mouse xenograft model. Induction of ER stress required the transcription factor ATF4, which directly bound the FGF19 promoter...
September 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28939077/genomic-characterization-of-tobacco-nut-chewing-hpv-negative-early-stage-tongue-tumors-identify-mmp10-asa-candidate-to-predict-metastases
#11
Pawan Upadhyay, Nilesh Gardi, Sanket Desai, Pratik Chandrani, Asim Joshi, Bhaskar Dharavath, Priyanca Arora, Munita Bal, Sudhir Nair, Amit Dutt
OBJECTIVES: Nodal metastases status among early stage tongue squamous cell cancer patients plays a decisive role in the choice of treatment, wherein about 70% patients can be spared from surgery with an accurate prediction of negative pathological lymph node status. This underscores an unmet need for prognostic biomarkers to stratify the patients who are likely to develop metastases. MATERIALS AND METHODS: We performed high throughput sequencing of fifty four samples derived from HPV negative early stage tongue cancer patients habitual of chewing betel nuts, areca nuts, lime or tobacco using whole exome (n=47) and transcriptome (n=17) sequencing that were analyzed using in-house computational tools...
October 2017: Oral Oncology
https://www.readbyqxmd.com/read/28938478/roux-en-y-gastric-bypass-surgery-has-unique-effects-on-postprandial-fgf21-but-not-fgf19-secretion
#12
COMPARATIVE STUDY
Lydia-Ann L S Harris, Gordon I Smith, Bettina Mittendorfer, J Christopher Eagon, Adewole L Okunade, Bruce W Patterson, Samuel Klein
Context: Fibroblast growth factor (FGF)19 and FGF21 are secreted by the intestine and liver in response to macronutrient intake. Intestinal resection and reconstruction via bariatric surgery may alter their regulation. Objective: We tested the hypothesis that weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery, but not matched weight loss induced by laparoscopic adjustable gastric banding (LAGB), increases postprandial plasma FGF19 and FGF21 concentrations...
October 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938455/bile-acid-alterations-are-associated-with-insulin-resistance-but-not-with-nash-in-obese-subjects
#13
Vanessa Legry, Sven Francque, Joel T Haas, An Verrijken, Sandrine Caron, Oscar Chávez-Talavera, Emmanuelle Vallez, Luisa Vonghia, Eveline Dirinck, Ann Verhaegen, Mostafa Kouach, Sophie Lestavel, Philippe Lefebvre, Luc Van Gaal, Anne Tailleux, Réjane Paumelle, Bart Staels
Context: Bile acids (BAs) are signaling molecules controlling energy homeostasis that can be both toxic and protective for the liver. BA alterations have been reported in obesity, insulin resistance (IR), and nonalcoholic steatohepatitis (NASH). However, whether BA alterations contribute to NASH independently of the metabolic status is unclear. Objective: To assess BA alterations associated with NASH independently of body mass index and IR. Design and Setting: Patients visiting the obesity clinic of the Antwerp University Hospital (a tertiary referral facility) were recruited from 2006 to 2014...
October 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28906590/fgf19-genetic-amplification-as-a-potential-therapeutic-target-in-lung-squamous-cell-carcinomas
#14
Xiaochen Zhang, Mei Kong, Zhen Zhang, Suzhen Xu, Feifei Yan, Liyuan Wei, Jianying Zhou
BACKGROUND: Although FGF19 gene aberrations are associated with carcinogenesis and progression in human cancers, the roles of FGF19 genetic amplification and expression in Chinese patients with lung squamous cell carcinoma (LSCC) and FGF19 amplification as a potential therapeutic target for LSCC are not well understood. METHODS: Fluorescence in situ hybridization analysis and quantitative real-time-PCR was used to detect FGF19 genetic amplification and FGF19 messenger RNA expression in LSCC tumor and paired adjacent samples...
November 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28894048/the-role-of-bile-acids-in-the-pathogenesis-of-bowel-diseases
#15
Magdalena Panek-Jeziorna, Agata Mulak
Bile acids not only play a cardinal role in the digestion and absorption of fat and fat-soluble vitamins, but also significantly affect gastrointestinal motor, sensory and secretory functions, intestinal barrier permeability and the regulation of the inflammatory response. The results of recent studies have revealed complex interactions between bile acids and the gut microbiota. In addition, bile acids also play a role of signaling molecules regulating the activity of lipid and glucose metabolic pathways, as well as a role of ligands for transcription factors...
August 24, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28865148/chronic-elevation-of-plasma-fgf19-in-long-term-fxr-agonist-therapy-a-happy-marriage-or-cause-for-oncologic-concern
#16
Frank G Schaap, Peter L M Jansen, Steven W M Olde Damink
No abstract text is available yet for this article.
September 2, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28774887/suppressed-hepatic-bile-acid-signalling-despite-elevated-production-of-primary-and-secondary-bile-acids-in-nafld
#17
Na Jiao, Susan S Baker, Adrian Chapa-Rodriguez, Wensheng Liu, Colleen A Nugent, Maria Tsompana, Lucy Mastrandrea, Michael J Buck, Robert D Baker, Robert J Genco, Ruixin Zhu, Lixin Zhu
OBJECTIVE: Bile acids are regulators of lipid and glucose metabolism, and modulate inflammation in the liver and other tissues. Primary bile acids such as cholic acid and chenodeoxycholic acid (CDCA) are produced in the liver, and converted into secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by gut microbiota. Here we investigated the possible roles of bile acids in non-alcoholic fatty liver disease (NAFLD) pathogenesis and the impact of the gut microbiome on bile acid signalling in NAFLD...
August 3, 2017: Gut
https://www.readbyqxmd.com/read/28768168/what-s-so-special-about-fgf19-unique-effects-reported-on-skeletal-muscle-mass-and-function
#18
David J Glass
In a recent study published in Nature Medicine, Benoit et al. (2017) reported unique effects of FGF19 on mouse skeletal muscle: FGF19 induced skeletal muscle hypertrophy and blocked muscle atrophy, acting via FGF receptors and ßKlotho, while a related FGF21 hormone was ineffective.
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28746779/hepatic-farnesoid-x-receptor-protein-level-and-circulating-fibroblast-growth-factor-19-concentration-in-children-with-nafld
#19
Valerio Nobili, Anna Alisi, Antonella Mosca, Claudia Della Corte, Silvio Veraldi, Rita De Vito, Cristiano De Stefanis, Valentina D'Oria, Joerg Jahnel, Evelyn Zohrer, Eleonora Scorletti, Christopher D Byrne
BACKGROUND & AIMS: Treatment with the farnesoid X receptor (FXR) agonist obeticholic acid is ineffective in some patients with non-alcoholic steatohepatitis (NASH) but the explanation is uncertain. We investigated hepatic FXR expression, and measurements of fibroblast growth factor 19 (FGF19) and bile acids (BAs) in children with NAFLD to investigate relationships with NASH. METHODS: 33 children with NAFLD who underwent diagnostic liver biopsy were studied. Hepatic FXR protein levels and circulating FGF19 concentrations were compared with those analysed in five control subjects with proven normal liver histology...
July 26, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28729723/muscle-disorders-fgf19-reduces-muscle-wasting
#20
Megan Cully
No abstract text is available yet for this article.
August 2017: Nature Reviews. Drug Discovery
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