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fibroblast growth factor liver disease

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https://www.readbyqxmd.com/read/28178326/quantitative-liver-proteomics-identifies-fgf19-targets-that-couple-metabolism-and-proliferation
#1
Vittoria Massafra, Alexandra Milona, Harmjan R Vos, Boudewijn M T Burgering, Saskia W C van Mil
Fibroblast growth factor 19 (FGF19) is a gut-derived peptide hormone that is produced following activation of Farnesoid X Receptor (FXR). FGF19 is secreted and signals to the liver, where it contributes to the homeostasis of bile acid (BA), lipid and carbohydrate metabolism. FGF19 is a promising therapeutic target for the metabolic syndrome and cholestatic diseases, but enthusiasm for its use has been tempered by FGF19-mediated induction of proliferation and hepatocellular carcinoma. To inform future rational design of FGF19-variants, we have conducted temporal quantitative proteomic and gene expression analyses to identify FGF19-targets related to metabolism and proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28145001/treatment-with-the-natural-fxr-agonist-chenodeoxycholic-acid-reduces-clearance-of-plasma-ldl-whilst-decreasing-circulating-pcsk9-lipoprotein-a-and-apolipoprotein-c-iii
#2
M Ghosh Laskar, M Eriksson, M Rudling, B Angelin
BACKGROUND: The natural farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA) suppresses hepatic cholesterol and bile acid synthesis and reduces biliary cholesterol secretion and triglyceride production. Animal studies have shown that bile acids downregulate hepatic LDL receptors (LDLRs); however, information on LDL metabolism in humans is limited. METHODS: Kinetics of autologous (125) I-LDL were determined in 12 male subjects at baseline and during treatment with CDCA (15 mg kg(-1) day(-1) )...
February 1, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28133764/neutrophils-promote-hepatic-metastasis-growth-through-fibroblast-growth-factor-fgf-2-dependent-angiogenesis
#3
Alex N Gordon-Weeks, Su Y Lim, Arseniy E Yuzhalin, Keaton Jones, Bostjan Markelc, Jon N Buzelli, Emmanouil Fokas, Yunhong Cao, Sean Smart, Ruth Muschel
: Hepatic metastases are amenable to ablation, however many patients are not suitable candidates for such therapy and recurrence is common. The tumor microenvironment is known to be essential for metastatic growth, yet identification of plausible targets for cancer therapy in the microenvironment has proven elusive. We found that human colorectal cancer liver metastases and murine gastrointestinal experimental liver metastases are infiltrated by neutrophils. Plasticity in neutrophils has recently been shown to lead to both pro- and anti- tumor effects...
January 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28131861/alcoholic-fatty-liver-is-enhanced-in-cyp2a5-knockout-mice-the-role-of-the-ppar%C3%AE-fgf21-axis
#4
Xue Chen, Stephen C Ward, Arthur I Cederbaum, Huabao Xiong, Yongke Lu
BACKGROUND & AIMS: Cytochrome P450 2A5 (CYP2A5) is induced by ethanol, and the ethanol induction of CYP2A5 is regulated by nuclear factor-erythroid 2-related factor 2 (NRF2). Cyp2a5 knockout (Cyp2a5(-/-)) mice develop more severe alcoholic fatty liver than Cyp2a5(+/+) mice. Fibroblast growth factor 21 (FGF21), a PPARα-regulated liver hormone, is involved in hepatic lipid metabolism. Alcoholic and non-alcoholic fatty liver are enhanced in Pparα knockout (Pparα(-/-)) mice. This study investigates the relationship between the PPARα-FGF21 axis and the enhanced alcoholic fatty liver in Cyp2a5(-/-) mice...
January 25, 2017: Toxicology
https://www.readbyqxmd.com/read/28102887/clinical-trial-of-nintedanib-in-patients-with-recurrent-or-metastatic-salivary-gland-cancer-of-the-head-and-neck-a-multicenter-phase-2-study-korean-cancer-study-group-hn14-01
#5
Youjin Kim, Su Jin Lee, Ji Yun Lee, Se-Hoon Lee, Jong-Mu Sun, Keunchil Park, Ho Jung An, Jae Yong Cho, Eun Joo Kang, Ha-Young Lee, Jinsoo Kim, Bhumsuk Keam, Hye Ryun Kim, Kyoung Eun Lee, Moon Young Choi, Ki Hyeong Lee, Myung-Ju Ahn
BACKGROUND: Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß)...
January 19, 2017: Cancer
https://www.readbyqxmd.com/read/28039838/fibroblast-growth-factor-21-and-its-novel-association-with-oxidative-stress
#6
REVIEW
Miguel Ángel Gómez-Sámano, Mariana Grajales-Gómez, Julia María Zuarth-Vázquez, Ma Fernanda Navarro-Flores, Mayela Martínez-Saavedra, Óscar Alfredo Juárez-León, Mariana G Morales-García, Víctor Manuel Enríquez-Estrada, Francisco J Gómez-Pérez, Daniel Cuevas-Ramos
Fibroblast growth factor 21 (FGF21) is an endocrine-member of the FGF family. It is synthesized mainly in the liver, but it is also expressed in adipose tissue, skeletal muscle, and many other organs. It has a key role in glucose and lipid metabolism, as well as in energy balance. FGF21 concentration in plasma is increased in patients with obesity, insulin resistance, and metabolic syndrome. Recent findings suggest that such increment protects tissue from an increased oxidative stress environment. Different types of physical stress, such as strenuous exercising, lactation, diabetic nephropathy, cardiovascular disease, and critical illnesses, also increase FGF21 circulating concentration...
December 22, 2016: Redox Biology
https://www.readbyqxmd.com/read/28012645/the-role-of-fibroblast-growth-factor-21-in-atherosclerosis
#7
REVIEW
John Kokkinos, Shudi Tang, Kerry-Anne Rye, Kwok Leung Ong
The metabolic properties of the endocrine fibroblast growth factor 21 (FGF21) have been extensively studied in the past decade. Previous studies have demonstrated the lipid-lowering, anti-inflammatory and anti-oxidant properties of FGF21. FGF21 is mainly secreted in the liver and adipose tissue in response to a range of physiological and pathological stimuli. In animal and in vitro studies, FGF21 has been shown to improve lipid profiles and inhibit key processes in the pathogenesis of atherosclerosis. It exerts its effects on the cardiovascular system via adiponectin dependent and independent mechanisms...
December 1, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27959632/the-role-of-cancer-associated-fibroblasts-and-fibrosisin-liver-cancer
#8
Silvia Affo, Le-Xing Yu, Robert F Schwabe
Liver cancer is the second leading cause of cancer mortality worldwide, causing more than 700,000 deaths annually. Because of the wide landscape of genomic alterations and limited therapeutic success of targeting tumor cells, a recent focus has been on better understanding and possibly targeting the microenvironment in which liver tumors develop. A unique feature of liver cancer is its close association with liver fibrosis. More than 80% of hepatocellular carcinomas (HCCs) develop in fibrotic or cirrhotic livers, suggesting an important role of liver fibrosis in the premalignant environment (PME) of the liver...
January 24, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/27939978/%C3%AE-1-adrenergic-receptor-downregulates-hepatic-fgf21-production-and-circulating-fgf21-levels-in-mice
#9
Katsunori Nonogaki, Takao Kaji
Fibroblast growth factor 21 (FGF21) is primarily secreted by the liver as an endocrine hormone and is suggested as a promising target for the treatment of metabolic diseases. FGF21 acts centrally to exert its effects on energy expenditure and body weight via the sympathetic nervous system in mice. Here we show that intraperitoneal injection of phentolamine (an α-adrenergic receptor antagonist, 5mg/kg) significantly increased plasma FGF21 levels compared with the saline controls in C57BL6J mice, whereas alprenolol (a β-adrenergic receptor antagonist, 6mg/kg) had no effect...
December 6, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27919710/the-transcription-factor-carbohydrate-response-element-binding-protein-chrebp-a-possible-link-between-metabolic-disease-and-cancer
#10
REVIEW
Katsumi Iizuka
Carbohydrate-response element-binding protein (ChREBP) has been identified as a transcription factor that binds to carbohydrate response element in the promoter of pyruvate kinase, liver and red blood cells. ChREBP is activated by metabolites derived from glucose and suppressed by adenosine monophosphate (AMP), ketone bodies and cyclic cAMP. ChREBP regulates gene transcription related to glucose and lipid metabolism. Findings from knockout mice and human subjects suggest that ChREBP helps to induce hepatic steatosis, dyslipidemia, and glucose intolerance...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27917437/nicotine-plus-a-high-fat-diet-triggers-cardiomyocyte-apoptosis
#11
Indrani Sinha-Hikim, Theodore C Friedman, Mark Falz, Victor Chalfant, Mohammad Kamrul Hasan, Jorge Espinoza-Derout, Desean L Lee, Carl Sims, Peter Tran, Sushil K Mahata, Amiya P Sinha-Hikim
Cigarette smoking is an important risk factor for diabetes, cardiovascular disease and non-alcoholic fatty liver disease. The health risk associated with smoking can be aggravated by obesity. Smoking might also trigger cardiomyocyte (CM) apoptosis. Given that CM apoptosis has been implicated as a potential mechanism in the development of cardiomyopathy and heart failure, we characterize the key signaling pathways in nicotine plus high-fat diet (HFD)-induced CM apoptosis. Adult C57BL6 male mice were fed a normal diet (ND) or HFD and received twice-daily intraperitoneal (IP) injections of nicotine (0...
December 5, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27904677/an-engineered-fgf21-variant-ly2405319-can-prevent-non-alcoholic-steatohepatitis-by-enhancing-hepatic-mitochondrial-function
#12
Ju Hee Lee, Yea Eun Kang, Joon Young Chang, Ki Cheol Park, Hyeon-Woo Kim, Jung Tae Kim, Hyun Jin Kim, Hyon-Seung Yi, Minho Shong, Hyo Kyun Chung, Koon Soon Kim
Non-alcoholic fatty liver disease (NAFLD) is a prevalent obesity-related disease that affects large populations throughout the world due to excessive calorie intake and an increasingly sedentary lifestyle. Fibroblast growth factor 21 (FGF21) has recently emerged as a promising therapeutic candidate for the treatment of obesity and diabetes. FGF21 is a starvation-induced pleiotropic hormone with various beneficial metabolic effects, and pharmacological treatment in rodents has been shown to improve insulin sensitivity and decrease simple fatty liver disease...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27832316/bone-derived-factors-a-new-gateway-to-regulate-glycemia
#13
Nicolas Bonnet
Type 2 diabetes mellitus (T2DM) and osteoporosis are two major disorders which prevalence increases with aging and is predicted to worsen in the coming years. Preclinical investigations suggest common mechanisms implicated in the pathogenesis of both disorders. Recent evidence has established that there is a clear link between glucose and bone metabolism. The emergence of bone as an endocrine regulator through FGF23 and osteocalcin has led to the re-evaluation of the role of bone cells and bone-derived factors in the development of metabolic diseases such as T2DM...
November 10, 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27765690/isocaloric-diets-high-in-animal-or-plant-protein-reduce-liver-fat-and-inflammation-in-individuals-with-type-2-diabetes
#14
Mariya Markova, Olga Pivovarova, Silke Hornemann, Stephanie Sucher, Turid Frahnow, Katrin Wegner, Jürgen Machann, Klaus Jürgen Petzke, Johannes Hierholzer, Ralf Lichtinghagen, Christian Herder, Maren Carstensen-Kirberg, Michael Roden, Natalia Rudovich, Susanne Klaus, Ralph Thomann, Rosemarie Schneeweiss, Sascha Rohn, Andreas F H Pfeiffer
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with increased risk of hepatic, cardiovascular, and metabolic diseases. High-protein diets, rich in methionine and branched chain amino acids (BCAAs), apparently reduce liver fat, but can induce insulin resistance. We investigated the effects of diets high in animal protein (AP) vs plant protein (PP), which differ in levels of methionine and BCAAs, in patients with type 2 diabetes and NAFLD. We examined levels of liver fat, lipogenic indices, markers of inflammation, serum levels of fibroblast growth factor 21 (FGF21), and activation of signaling pathways in adipose tissue...
February 2017: Gastroenterology
https://www.readbyqxmd.com/read/27708340/activation-and-increase-of-radio-sensitive-cd11b-recruited-kupffer-cells-macrophages-in-diet-induced-steatohepatitis-in-fgf5-deficient-mice
#15
Hiroyuki Nakashima, Masahiro Nakashima, Manabu Kinoshita, Masami Ikarashi, Hiromi Miyazaki, Hiromi Hanaka, Junko Imaki, Shuhji Seki
We have recently reported that Kupffer cells consist of two subsets, radio-resistant resident CD68+ Kupffer cells and radio-sensitive recruited CD11b+ Kupffer cells/macrophages (Mφs). Non-alcoholic steatohepatitis (NASH) is characterized not only by hepatic steatosis but also chronic inflammation and fibrosis. In the present study, we investigated the immunological mechanism of diet-induced steatohepatitis in fibroblast growth factor 5 (FGF5) deficient mice. After consumption of a high fat diet (HFD) for 8 weeks, FGF5 null mice developed severe steatohepatitis and fibrosis resembling human NASH...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27666676/myeloid-cell-specific-lipin-1-deficiency-stimulates-endocrine-adiponectin-fgf15-axis-and-ameliorates-ethanol-induced-liver-injury-in-mice
#16
Jiayou Wang, Chunki Kim, Alvin Jogasuria, Yoonhee Han, Xudong Hu, Jiashin Wu, Hong Shen, Roman Chrast, Brian N Finck, Min You
Lipin-1 is a phosphatidate phosphohydrolase (PAP) required for the generation of diacylglycerol during glycerolipid synthesis, and exhibits dual functions in the regulation of lipid metabolism. Lipin-1 has been implicated in the pathogenesis of alcoholic liver disease (ALD). In the present study, we assessed lipin-1 function in myeloid cells in ALD using a myeloid cell-specific lipin-1 knockout (mLipin-1KO) mouse model. Utilizing the Gao-binge ethanol feeding protocol, matched mLipin-1KO mice and littermate loxP control (WT) mice were pair-fed with either an ethanol-containing diet or an ethanol-free diet (control)...
September 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27646933/current-and-upcoming-pharmacotherapy-for-non-alcoholic-fatty-liver-disease
#17
REVIEW
Yaron Rotman, Arun J Sanyal
Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress...
January 2017: Gut
https://www.readbyqxmd.com/read/27631137/the-suppression-of-hepatic-glucose-production-improves-metabolism-and-insulin-sensitivity-in-subcutaneous-adipose-tissue-in-mice
#18
Sylvie Casteras, Aya Abdul-Wahed, Maud Soty, Fanny Vulin, Hervé Guillou, Mélanie Campana, Hervé Le Stunff, Luciano Pirola, Fabienne Rajas, Gilles Mithieux, Amandine Gautier-Stein
AIMS/HYPOTHESIS: Despite the strong correlation between non-alcoholic fatty liver disease and insulin resistance, hepatic steatosis is associated with greater whole-body insulin sensitivity in several models. We previously reported that the inhibition of hepatic glucose production (HGP) protects against the development of obesity and diabetes despite severe steatosis, thanks to the secretion of specific hepatokines such as fibroblast growth factor 21 (FGF21) and angiopoietin-related growth factor...
September 9, 2016: Diabetologia
https://www.readbyqxmd.com/read/27580383/alterations-in-enterohepatic-fgf15-signaling-and-changes-in-bile-acid-composition-depend-on-localization-of-murine-intestinal-inflammation
#19
Monika Rau, Bruno Stieger, Maria J Monte, Johannes Schmitt, Daniel Jahn, Isabelle Frey-Wagner, Tina Raselli, Jose J G Marin, Beat Müllhaupt, Gerhard Rogler, Andreas Geier
BACKGROUND: Fibroblast growth factor (FGF) 15/19 is part of the gut-liver crosstalk accounting for bile acid (BA) metabolism regulation. Dysregulation of fibroblast growth factor 15/19 signaling is observed in different pathological conditions, for example, in gastrointestinal diseases such as inflammatory bowel disease (IBD). To understand the molecular bases, we analyzed the enterohepatic regulation of Fgf15-mediated pathway in 2 different inflammatory bowel disease mouse models. METHODS: Target genes of the BA-farnesoid-X-receptor (Fxr)-Ffg15 axis were quantified by RT-PCR or western blotting in gut and liver of dextran sulfate sodium (DSS)-treated and IL10 mice...
October 2016: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/27548521/a-liver-stress-endocrine-nexus-promotes-metabolic-integrity-during-dietary-protein-dilution
#20
Adriano Maida, Annika Zota, Kim A Sjøberg, Jonas Schumacher, Tjeerd P Sijmonsma, Anja Pfenninger, Marie M Christensen, Thomas Gantert, Jessica Fuhrmeister, Ulrike Rothermel, Dieter Schmoll, Mathias Heikenwälder, Juan L Iovanna, Kerstin Stemmer, Bente Kiens, Stephan Herzig, Adam J Rose
Dietary protein intake is linked to an increased incidence of type 2 diabetes (T2D). Although dietary protein dilution (DPD) can slow the progression of some aging-related disorders, whether this strategy affects the development and risk for obesity-associated metabolic disease such as T2D is unclear. Here, we determined that DPD in mice and humans increases serum markers of metabolic health. In lean mice, DPD promoted metabolic inefficiency by increasing carbohydrate and fat oxidation. In nutritional and polygenic murine models of obesity, DPD prevented and curtailed the development of impaired glucose homeostasis independently of obesity and food intake...
September 1, 2016: Journal of Clinical Investigation
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