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fibroblast growth factor liver disease

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https://www.readbyqxmd.com/read/29770125/fgf23-actions-on-target-tissues-with-and-without-klotho
#1
REVIEW
Beatrice Richter, Christian Faul
Fibroblast growth factor (FGF) 23 is a phosphaturic hormone whose physiologic actions on target tissues are mediated by FGF receptors (FGFR) and klotho, which functions as a co-receptor that increases the binding affinity of FGF23 for FGFRs. By stimulating FGFR/klotho complexes in the kidney and parathyroid gland, FGF23 reduces renal phosphate uptake and secretion of parathyroid hormone, respectively, thereby acting as a key regulator of phosphate metabolism. Recently, it has been shown that FGF23 can also target cell types that lack klotho...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29753678/deficiency-of-fibroblast-growth-factor-21-fgf21-promotes-hepatocellular-carcinoma-hcc-in-mice-on-a-long-term-obesogenic-diet
#2
Garima Singhal, Gaurav Kumar, Suzanne Chan, Ffolliott M Fisher, Yong Ma, Hilde G Vardeh, Imad A Nasser, Jeffrey S Flier, Eleftheria Maratos-Flier
OBJECTIVE: Non-alcoholic fatty liver (NAFL) associated with obesity is a major cause of liver diseases which can progress to non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) plays an important role in liver metabolism and is also a potential marker for NAFL. Here we aimed to test the effect of FGF21 deficiency on liver pathology in mice consuming a conventional high fat, high sucrose (HFHS) obesogenic diet for up to 52 weeks...
March 8, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29735309/the-elevation-of-circulating-fibroblast-growth-factor-23-without-kidney-disease-does-not-increase-cardiovascular-disease-risk
#3
Eva-Maria Pastor-Arroyo, Nicole Gehring, Christiane Krudewig, Sarah Costantino, Carla Bettoni, Thomas Knöpfel, Sibylle Sabrautzki, Bettina Lorenz-Depiereux, Johanne Pastor, Tim M Strom, Martin Hrabě de Angelis, Giovanni G Camici, Francesco Paneni, Carsten A Wagner, Isabel Rubio-Aliaga
High circulating fibroblast growth factor 23 (FGF23) levels are probably a major risk factor for cardiovascular disease in chronic kidney disease. FGF23 interacts with the receptor FGFR4 in cardiomyocytes inducing left ventricular hypertrophy. Moreover, in the liver FGF23 via FGFR4 increases the risk of inflammation which is also found in chronic kidney disease. In contrast, X-linked hypophosphatemia is characterized by high FGF23 circulating levels due to loss of function mutations of the phosphate-regulating gene with homologies to an endopeptidase on the X chromosome (PHEX), but is not characterized by high cardiovascular morbidity...
May 5, 2018: Kidney International
https://www.readbyqxmd.com/read/29727594/fibroblast-growth-factor-21-a-versatile-regulator-of-metabolic-homeostasis
#4
Lucas D BonDurant, Matthew J Potthoff
Fibroblast growth factor 21 (FGF21) is an endocrine hormone derived from the liver that exerts pleiotropic effects on the body to maintain overall metabolic homeostasis. During the past decade, there has been an enormous effort made to understand the physiological roles of FGF21 in regulating metabolism and to identify the mechanism for its potent pharmacological effects to reverse diabetes and obesity. Through both human and rodent studies, it is now evident that FGF21 levels are dynamically regulated by nutrient sensing, and consequently FGF21 functions as a critical regulator of nutrient homeostasis...
May 4, 2018: Annual Review of Nutrition
https://www.readbyqxmd.com/read/29704003/pilot-study-with-ibat-inhibitor-a4250-for-the-treatment-of-cholestatic-pruritus-in-primary-biliary-cholangitis
#5
Samer Al-Dury, Annika Wahlström, Staffan Wahlin, Jacqueline Langedijk, Ronald Oude Elferink, Marcus Ståhlman, Hanns-Ulrich Marschall
Pruritus is a common complication of cholestatic liver diseases. Inhibition of the ileal bile acid transporter (IBAT/ASBT) may emerge as treatment option. Our aim was to assess tolerability and effect on pruritus of the selective IBAT inhibitor A4250 in patients with primary biliary cholangitis (PBC). Ten patients with PBC and bile acid sequestrant treatment of cholestatic pruritus were after a two-week wash out of the bile acid sequestrant treated with either 0.75 mg (n = 4) or 1.5 mg (n = 5) of A4250 for four weeks...
April 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29701901/no-gut-no-gain-enteral-bile-acid-treatment-preserves-gut-growth-but-not-parenteral-nutrition-associated-liver-injury-in-a-novel-extensive-short-bowel-animal-model
#6
Gustavo Villalona, Amber Price, Keith Blomenkamp, Chandrashekhara Manithody, Saurabh Saxena, Thomas Ratchford, Matthew Westrich, Vindhya Kakarla, Shruthika Pochampally, William Phillips, Nicole Heafner, Niraja Korremla, Jose Greenspon, Miguel A Guzman, Ajay Kumar Jain
BACKGROUND: Parenteral nutrition (PN) provides nutrition intravenously; however, this life-saving therapy is associated with significant liver disease. Recent evidence indicates improvement in PN-associated injury in animals with intact gut treated with enteral bile acid (BA), chenodeoxycholic acid (CDCA), and a gut farnesoid X receptor (FXR) agonist, which drives the gut-liver cross talk (GLCT). We hypothesized that similar improvement could be translated in animals with short bowel syndrome (SBS)...
April 27, 2018: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29698569/preemptive-activation-of-the-integrated-stress-response-protects-mice-from-diet-induced-obesity-and-insulin-resistance-via-fibroblast-growth-factor-21-induction
#7
Xu Xu, Christopher Krumm, Jae-Seon So, Curtis J Bare, Corey Holman, Jesper Gromada, David E Cohen, Ann-Hwee Lee
The integrated stress response (ISR) is a signaling system in which the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) by stress-specific kinases and the subsequent activation of activation transcription factor (ATF) 4 help restore cellular homeostasis following exposure to environmental stresses. ISR activation has been observed in metabolic diseases including hepatic steatosis, steatohepatitis and insulin resistance, but it remains unclear whether ISR contributes to the disease pathogenesis, or represents an innate defense mechanism against metabolic stresses...
April 26, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29696080/therapeutic-effects-of-serum-extracellular-vesicles-in-liver-fibrosis
#8
Li Chen, Ruju Chen, Sherri Kemper, Min Cong, Hong You, David R Brigstock
The lack of approved therapies for hepatic fibrosis seriously limits medical management of patients with chronic liver disease. Since extracellular vesicles (EVs) function as conduits for intercellular molecular transfer, we investigated if EVs from healthy individuals have anti-fibrotic properties. Hepatic fibrogenesis or fibrosis in carbon tetrachloride (CCl4 )- or thioacetic acid-induced liver injury models in male or female mice were suppressed by serum EVs from normal mice (EVN) but not from fibrotic mice (EVF)...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29653185/sex-differences-in-the-development-of-hepatic-steatosis-in-cafeteria-diet-induced-obesity-in-young-mice
#9
Fabiana Rodrigues Silva Gasparin, Fernando Olinto Carreño, Juliana Moraes Mewes, Eduardo Hideo Gilglioni, Clairce Luzia Salgueiro Pagadigorria, Maria Raquel Marçal Natali, Karina Sayuri Utsunomiya, Rodrigo Polimeni Constantin, Amanda Tomie Ouchida, Carlos Curti, Ingrid C Gaemers, Ronald Petrus Johannes Oude Elferink, Jorgete Constantin, Emy Luiza Ishii-Iwamoto
The present study was planned to improve our understanding about sex differences in the development of hepatic steatosis in cafeteria diet-induced obesity in young mice. Female (FCaf) and male (MCaf) mice fed a cafeteria diet had similar body weight gain and adiposity index, but FCaf had a more extensive steatosis than MCaf. FCaf livers exhibited a higher non-alcoholic fatty liver disease activity score, elevated lipid percentage area (+34%) in Sudan III staining and increased TG content (+25%) compared to MCaf...
April 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29618028/hepatic-production-of-fibroblast-growth-factor-23-in-autosomal-dominant-polycystic-kidney-disease
#10
Frank Bienaimé, Ariane Ambolet, Béatrice Aussilhou, François Brazier, Marie Fouchard, Amandine Viau, Pauline Barre, Anne-Marie Tissier, Jean-Michel Correas, Valérie Paradis, Fabiola Terzi, Gérard Friedlander, Bertrand Knebelmann, Dominique Joly, Dominique Prié
Context: the bone-derived hormone fibroblast growth factor 23 (FGF23) controls phosphate homeostasis and urinary phosphate excretion. FGF23 plasma levels increase at the early step of renal insufficiency to prevent hyperphosphatemia. Recent evidence suggests that this increase has off-target effects on cardiac and immune cells that compromises patients' health. Subjects with autosomal dominant polycystic kidney disease (ADPKD) have been reported to display higher FGF23 concentrations than non-ADPKD patients with similar renal function...
March 29, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29574933/the-association-of-serum-fgf23-and-non-alcoholic-fatty-liver-disease-is-independent-of-vitamin-d-in-type-2-diabetes-patients
#11
Xingxing He, Yun Shen, Xiaojing Ma, Lingwen Ying, Jiahui Peng, Xiaoping Pan, Yuqian Bao, Jian Zhou
Recent studies have showed that circulating fibroblast growth factor (FGF) 23 and vitamin D levels were closely correlated with insulin resistance. The aim of this study was to investigate the relationship among serum FGF 23 level, serum 25-hydroxyvitamin D [25(OH)D] levels, and non-alcoholic fatty liver disease (NAFLD) in Chinese patients with type 2 diabetes mellitus (T2DM). This study enrolled 331 hospitalized T2DM patients (209 patients with NAFLD and 122 patients without NAFLD). Serum FGF23 levels were measured using a sandwich enzyme-linked immunosorbent assay...
March 25, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29558905/novel-biomarker-based-model-for-the-prediction-of-sorafenib-response-and-overall-survival-in-advanced-hepatocellular-carcinoma-a-prospective-cohort-study
#12
Hwi Young Kim, Dong Hyeon Lee, Jeong-Hoon Lee, Young Youn Cho, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
BACKGROUND: Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). METHODS: This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib...
March 20, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29545834/human-fibroblast-growth-factor-21-serves-as-a-predictor-and-prognostic-factor-in-patients-with-hepatitis-b-cirrhosis-combined-with-adrenal-insufficiency
#13
Jian Zhang, Junhong Li, Junwei Ma, Hongxin Wang, Yin Yi
Hepatitis B cirrhosis is caused by liver cell necrosis, residual liver cell nodular regeneration, connective tissue hyperplasia and fiber formation, which frequently leads to adrenal insufficiency. Previous reports have demonstrated that human fibroblast growth factor (hFGF)-21 is a multifunctional protein that exhibits potential therapeutic value for metabolic diseases. The present study investigated the diagnostic value of hFGF-21 and analyzed the potential molecular mechanism in the progression of hepatitis B cirrhosis combined with adrenal insufficiency...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29486523/intestine-farnesoid-x-receptor-agonist-and-the-gut-microbiota-activate-g-protein-bile-acid-receptor-1-signaling-to-improve-metabolism
#14
Preeti Pathak, Xie Cen, Robert G Nichols, Jessica M Ferrell, Shannon Boehme, Kristopher W Krausz, Andrew D Patterson, Frank J Gonzalez, John Y L Chiang
Bile acids activate farnesoid X receptor (FXR) and G protein-coupled bile acid receptor-1 (Gpbar-1, aka TGR5) to regulate bile acid metabolism and glucose and insulin sensitivity. FXR and TGR5 are co-expressed in the enteroendocrine L cells but their roles in integrated regulation of metabolism are not completely understood. We reported recently that activation of FXR induces TGR5 to stimulate glucagon-like peptide-1 (GLP-1) secretion to improve insulin sensitivity and hepatic metabolism. In this study, we used the intestine-restricted FXR agonist fexaramine (FEX) to study the effect of activation of intestinal FXR on the gut microbiome, bile acid metabolism, and FXR and TGR5 signaling...
February 27, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29452367/variant-in-human-pofut1-reduces-enzymatic-activity-and-likely-causes-a-recessive-microcephaly-global-developmental-delay-with-cardiac-and-vascular-features
#15
Hideyuki Takeuchi, Derek Wong, Michael Schneider, Hudson H Freeze, Megumi Takeuchi, Steven J Berardinelli, Atsuko Ito, Hane Lee, Stanley F Nelson, Robert S Haltiwanger
Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects. Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe Notch-like phenotypes including defects in somitogenesis, cardiogenesis, vasculogenesis, and neurogenesis, but the extent to which POFUT1 is required for normal human development is not yet understood...
February 14, 2018: Glycobiology
https://www.readbyqxmd.com/read/29451701/phase-1b-study-of-pasireotide-everolimus-and-selective-internal-radioembolization-therapy-for-unresectable-neuroendocrine-tumors-with-hepatic-metastases
#16
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
May 1, 2018: Cancer
https://www.readbyqxmd.com/read/29448103/fgf-21-deficiency-slows-gastric-emptying-and-reduces-initial-blood-alcohol-concentration-in-mice-exposed-to-acute-alcohol-in-fasting-state
#17
Guicheng Wu, Yanlong Liu, Yunhuan Liu, Lihua Zhang, Haiyang Zhao, Liming Liu, Cuiqing Zhao, Wenke Feng
Excess alcohol consumption can lead to alcoholic liver disease. Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple physiologic functions. Previous study demonstrated that FGF21 deficiency exacerbated alcohol-induced liver injury and exogenous FGF21 administration protected liver from chronic alcohol-induced injury. In this study, we aimed to explore the role of FGF21 in alcohol metabolism in mice. FGF21 knockout (KO) mice and the wild type(WT) control mice were divided into two groups and fasted for 24 h followed by a bonus of alcohol treatment at a dose of 5 g/kg body weight via gavage...
February 26, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29404440/engineered-fgf19-eliminates-bile-acid-toxicity-and-lipotoxicity-leading-to-resolution-of-steatohepatitis-and-fibrosis-in-mice
#18
Mei Zhou, R Marc Learned, Stephen J Rossi, Alex M DePaoli, Hui Tian, Lei Ling
Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease for which no approved therapies are available. Despite intensive research, the cellular mechanisms that mediate NAFLD pathogenesis and progression are poorly understood. Although obesity, diabetes, insulin resistance, and related metabolic syndrome, all consequences of a Western diet lifestyle, are well-recognized risk factors for NAFLD development, dysregulated bile acid metabolism is emerging as a novel mechanism contributing to NAFLD pathogenesis...
December 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29399808/disease-prevention-and-delayed-aging-by-dietary-sulfur-amino-acid-restriction-translational-implications
#19
REVIEW
Zhen Dong, Raghu Sinha, John P Richie
Sulfur amino acids (SAAs) play numerous critical roles in metabolism and overall health maintenance. Preclinical studies have demonstrated that SAA-restricted diets have many beneficial effects, including extending life span and preventing the development of a variety of diseases. Dietary sulfur amino acid restriction (SAAR) is characterized by chronic restrictions of methionine and cysteine but not calories and is associated with reductions in body weight, adiposity and oxidative stress, and metabolic changes in adipose tissue and liver resulting in enhanced insulin sensitivity and energy expenditure...
February 5, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29378767/perilipin-5-deletion-unmasks-an-endoplasmic-reticulum-stress-fibroblast-growth-factor-21-axis-in-skeletal-muscle
#20
Magdalene K Montgomery, Ruzaidi Mokhtar, Jacqueline Bayliss, Helena C Parkington, Victor M Suturin, Clinton R Bruce, Matthew J Watt
Lipid droplets (LDs) are critical for the regulation of lipid metabolism, and dysregulated lipid metabolism contributes to the pathogenesis of several diseases, including type 2 diabetes. We generated mice with muscle-specific deletion of the LD-associated protein perilipin 5 (PLIN5, Plin5MKO ) and investigated PLIN5's role in regulating skeletal muscle lipid metabolism, intracellular signaling, and whole-body metabolic homeostasis. High-fat feeding induced changes in muscle lipid metabolism of Plin5MKO mice, which included increased fatty acid oxidation and oxidative stress but, surprisingly, a reduction in inflammation and endoplasmic reticulum (ER) stress...
April 2018: Diabetes
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