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fibroblast growth factor liver disease

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https://www.readbyqxmd.com/read/28872123/ileectomy-induced-bile-overaccumulation-in-mouse-intestine
#1
Rongli Zhang, Jonathan W Ray, Mukesh K Jain, Shuxin Han
Intestinal resection is a common therapeutic approach for human diseases such as obesity, inflammatory bowel disease, Crohn's disease, and colon cancer that often results in severe short bowel syndrome-like adverse effects including bile acid diarrhea, dehydration, electrolyte disturbances, and nutrient malabsorption. Here we introduce a murine ileal resection model, termed ileectomy, to evaluate tissue communication and the maintenance of systemic homeostasis. After ileal resection, circulating blood is permanently devoid of the ileum-specific endocrine hormone fibroblast growth factor 15 (FGF15), which releases its endocrinal inhibition of bile acid synthesis in the liver...
August 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28855398/targeting-the-vascular-and-perivascular-niches-as-a-regenerative-therapy-for-lung-and-liver-fibrosis
#2
Zhongwei Cao, Tinghong Ye, Yue Sun, Gaili Ji, Koji Shido, Yutian Chen, Lin Luo, Feifei Na, Xiaoyan Li, Zhen Huang, Jane L Ko, Vivek Mittal, Lina Qiao, Chong Chen, Fernando J Martinez, Shahin Rafii, Bi-Sen Ding
The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. We show that targeting both the vascular niche and perivascular fibroblasts establishes "hospitable soil" to foster the incorporation of "seed," in this case, the engraftment of parenchymal cells in injured organs...
August 30, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28820393/fibroblast-growth-factor-21-and-omentin-1-hepatic-mrna-expression-and-serum-levels-in-morbidly-obese-women-with-non-alcoholic-fatty-liver-disease
#3
M Waluga, M Kukla, M Zorniak, M Kajor, L Liszka, M Dyaczynski, G Kowalski, D Zadlo, E Waluga, P Olczyk, R J Buldak, A Berdowska, M Hartleb
Fibroblast growth factor-21 (FGF21) and omentin-1 have been recognized as potent antidiabetic agents with potential hepatoprotective activity. The aim of this study was to evaluate hepatic FGF21 and omentin-1 mRNA expression as well as their serum levels as predictive markers of liver injury and insulin resistance in morbidly obese women with non-alcoholic fatty liver disease (NAFLD). This study included 56 severely obese women who underwent intraoperative wedge liver biopsy during the bariatric surgery. Hepatic FGF21 and omentin-1 mRNA were assessed by quantitative real-time PCR, while their serum concentrations were measured with commercially available enzyme-linked immunosorbent assays...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28795382/liver-adipose-tissue-crosstalk-a-key-player-in-the-pathogenesis-of-glucolipid-metabolic-disease
#4
De-Wei Ye, Xiang-Lu Rong, Ai-Min Xu, Jiao Guo
Glucolipid metabolic disease (GLMD), a complex of interrelated disorders in glucose and lipid metabolism, has become one of the leading chronic diseases causing public and clinical problem worldwide. As the metabolism of lipid and glucose is a highly coordinated process under both physiological and diseased conditions, the impairment in the signals corresponding to the metabolism of either lipid or glucose represents the common mechanism underlying the pathogenesis of GLMD. The liver and adipose tissue are the major metabolic organs responsible for energy utilization and storage, respectively...
June 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28774887/suppressed-hepatic-bile-acid-signalling-despite-elevated-production-of-primary-and-secondary-bile-acids-in-nafld
#5
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/28756207/pregnane-x-receptor-pxr-deficiency-improves-high-fat-diet-induced-obesity-via-induction-of-fibroblast-growth-factor-15-fgf15-expression
#6
Li-Yang Zhao, Jia-Yi Xu, Zhe Shi, Neal A Englert, Shu-Yun Zhang
Obesity has become a significant global health problem, and is a high risk factor for a variety of metabolic diseases. Fibroblast growth factor (FGF) 15 plays an important role in the regulation of metabolism. Xenobiotic-sensing nuclear receptors pregnane X receptor (PXR/NR1I2) and constitutive androstane receptor (CAR/NR1I3) play important roles in xenobiotic detoxification and metabolism, and also are involved in the regulation of energy metabolism. However, the effects that PXR and CAR have on the regulation of FGF15 are unknown...
July 26, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28728751/a-phase-ii-evaluation-of-brivanib-in-the-treatment-of-persistent-or-recurrent-carcinoma-of-the-cervix-an-nrg-oncology-gynecologic-oncology-group-study
#7
John K Chan, Wei Deng, Robert V Higgins, Krishnansu S Tewari, Albert J Bonebrake, Michael Hicks, Stephanie Gaillard, Pedro T Ramirez, Weldon Chafe, Bradley J Monk, Carol Aghajanian
BACKGROUND: Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients. METHODS: Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity...
July 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28698650/complementary-role-of-fibroblast-growth-factor-21-and-cytokeratin-18-in-monitoring-the-different-stages-of-nonalcoholic-fatty-liver-disease
#8
Guangyu Wu, Huating Li, Qichen Fang, Jing Zhang, Mingliang Zhang, Lei Zhang, Liang Wu, Xuhong Hou, Junxi Lu, Yuqian Bao, Weiping Jia
Fibroblast growth factor 21 (FGF21) and cytokeratin 18 (CK18) were previously reported to be elevated in nonalcoholic fatty liver disease (NAFLD). We aim to analyze the differential roles of FGF21, cell apoptosis marker CK18 fragment M30 and total cell death marker CK18 M65ED in monitoring the different stages of NAFLD spectrum in a population-based prospective cohort comprising 808 Chinese subjects. Predictive performances for monitoring the different stages of NAFLD were assessed by logistic regression and receiver-operating characteristic (ROC) curves...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673684/the-effect-of-fibroblast-growth-factor-15-deficiency-on-the-development-of-high-fat-diet-induced-non-alcoholic-steatohepatitis
#9
J D Schumacher, B Kong, Y Pan, L Zhan, R Sun, J Aa, D Rizzolo, J R Richardson, A Chen, M Goedken, L M Aleksunes, D L Laskin, G L Guo
Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease (NAFLD) characterized by steatosis, inflammation, and fibrosis often associated with metabolic syndrome. Fibroblast growth factor 15 (FGF15), an endocrine factor mainly produced in the distal part of small intestine, has emerged to be a critical factor in regulating bile acid homeostasis, energy metabolism, and liver regeneration. We hypothesized that FGF15 alters the development of each of the listed features of NASH. To test this hypothesis, four-week old male Fgf15(-/-) and their corresponding wild-type (WT) mice were fed either a high fat diet (HFD) or a control chow diet for six months...
September 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28651670/alterations-in-vitamin-a-retinoic-acid-homeostasis-in-diet-induced-obesity-and-insulin-resistance
#10
Nimesh Mody
Vitamin A is an essential micronutrient for life and the phytochemical β-carotene, also known as pro-vitamin A, is an important dietary source of this vitamin. Vitamin A (retinol) is the parent compound of all bioactive retinoids but it is retinoic acid (RA) that is the active metabolite of vitamin A. The plasma concentration of retinol is maintained in a narrow range and its normal biological activities strictly regulated since excessive intake can lead to toxicity and thus also be detrimental to life. The present review will give an overview of how vitamin A homeostasis is maintained and move on to focus on the link between circulating vitamin A and metabolic disease states...
June 27, 2017: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/28651327/alpha-klotho-and-fibroblast-growth-factor-23-among-alcoholics
#11
Geraldine Quintero-Platt, Emilio González-Reimers, Melchor Rodríguez-Gaspar, Candelaria Martín-González, Onán Pérez-Hernández, Lucía Romero-Acevedo, Elisa Espelosín-Ortega, María José de la Vega-Prieto, Francisco Santolaria-Fernández
Aims: Alcoholism may be a cardiovascular risk factor. Osteocyte derived molecules such as fibroblast growth factor 23 (FGF-23) and soluble α Klotho have recently been associated with cardiovascular disease, but their role in alcoholics is unknown. We here analyze the behavior of FGF23 and α Klotho in alcoholics. Methods: Ninety-seven alcoholic patients were assessed for liver function, presence of hypertension, diabetes, atrial fibrillation, left ventricular hypertrophy (LVH), vascular calcifications (assessed by chest X-ray) and nutritional status (lean and fat mass measured by densitometry)...
September 1, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/28584629/role-of-the-microrna-29-family-in-fibrotic-skin-diseases
#12
Duygu Harmanci, Erdogan Pekcan Erkan, Ayse Kocak, Gul Guner Akdogan
Fibrotic skin diseases are characterized by the accumulation of collagen. The hallmarks of fibrotic skin diseases are unbalanced fibroblast proliferation and differentiation, extracellular matrix production and transforming growth factor-β signalling. Numerous studies have investigated the possibility that microRNAs (miRNAs or miRs) are involved in the pathogenesis of certain fibrotic diseases, including skin, heart, lung and liver diseases. miRNAs are a class of small non-coding RNAs, which modify gene expression by binding to target messenger RNA (mRNA) and blocking the translation or inducing the degradation of target mRNA...
June 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28559437/fibroblast-growth-factor-21-a-regulator-of-metabolic-disease-and-health-span
#13
Ting Xie, Po Sing Leung
Fibroblast growth factor 21 (FGF21) is a potent endocrine regulator with physiological effects on glucose and lipid metabolism and thus garners much attention on its translational potential for the management of obesity and related metabolic syndromes. FGF21 is mainly expressed in several metabolically active tissue organs, such as the liver, adipose tissue, skeletal muscle and pancreas with profound effects and therapeutically relevance. Emerging experimental and clinical data point to the demonstrated metabolic benefits of FGF21 which includes, but not limit to, weight loss, glucose and lipid metabolism as well as insulin sensitivity...
May 30, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28549912/fatty-liver-and-fgf21-physiology
#14
REVIEW
Eleftheria Maratos-Flier
Non alcoholic fatty liver disease is linked to obesity and the metabolic syndrome. As rates of obesity rise it has become the major etiology of liver dysfunction. Despite intense study the molecular mechanisms contributing to the onset of fatty liver remain debatable. Furthermore, few therapies exist and as a result dietary therapy is commonly prescribed and remains problematic. Fibroblast growth factor is a complex metabolic regulator that is synthesized in multiple organs including the liver, with resulting complex systemic effects...
May 23, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28511023/efficacy-of-docosahexaenoic-acid-choline-vitamin-e-in-paediatric-nash-a-randomized-controlled-clinical-trial
#15
Evelyn Zöhrer, Anna Alisi, Jörg Jahnel, Antonella Mosca, Claudia Della Corte, Annalisa Crudele, Günter Fauler, Valerio Nobili
Nonalcoholic steatohepatitis (NASH), a progressive form of nonalcoholic fatty liver disease, is one of the most common hepatic diseases in children. We conducted a randomized controlled clinical trial on children with biopsy-proven NASH based on a combinatorial nutritional approach compared with placebo. Participants were assigned to lifestyle modification plus placebo or lifestyle modification plus a mix containing docosahexaenoic acid, choline, and vitamin E (DHA-CHO-VE). Forty children and adolescents participated in the entire trial...
May 16, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28467924/fgf21-is-a-sugar-induced-hormone-associated-with-sweet-intake-and-preference-in-humans
#16
Susanna Søberg, Camilla H Sandholt, Naja Z Jespersen, Ulla Toft, Anja L Madsen, Stephanie von Holstein-Rathlou, Trisha J Grevengoed, Karl B Christensen, Wender L P Bredie, Matthew J Potthoff, Thomas P J Solomon, Camilla Scheele, Allan Linneberg, Torben Jørgensen, Oluf Pedersen, Torben Hansen, Matthew P Gillum, Niels Grarup
The liking and selective ingestion of palatable foods-including sweets-is biologically controlled, and dysfunction of this regulation may promote unhealthy eating, obesity, and disease. The hepatokine fibroblast growth factor 21 (FGF21) reduces sweet consumption in rodents and primates, whereas knockout of Fgf21 increases sugar consumption in mice. To investigate the relevance of these findings in humans, we genotyped variants in the FGF21 locus in participants from the Danish Inter99 cohort (n = 6,514) and examined their relationship with a detailed range of food and ingestive behaviors...
May 2, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28445152/multiplexed-gene-expression-profiling-identifies-the-fgfr4-pathway-as-a-novel-biomarker-in-intrahepatic-cholangiocarcinoma
#17
Changhoon Yoo, Jihoon Kang, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Seung-Mo Hong, Jung Jin Hwang, Seong-Yun Jeong, Shin Hwang, Ki-Hun Kim, Young-Joo Lee, Klaus P Hoeflich, Oleg Schmidt-Kittler, Stephen Miller, Eun Kyung Choi
BACKGROUND: The fibroblast growth factor receptor 4 (FGFR4) pathway is an essential regulatory component of bile acid synthesis, and its relationship with hepatocellular carcinoma (HCC) has been reported. We investigated the gene expression and clinical significance of FGFR4 and related pathways in intrahepatic cholangiocarcinoma (iCCA). RESULTS: The median age was 56 years (range 30-78) and 34 patients (74%) were male. Six patients (13%) had hepatitis B virus infection, with or without liver cirrhosis...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415887/amelioration-of-late-onset-hepatic-steatosis-in-idh2-deficient-mice
#18
Su Jeong Lee, Hanvit Cha, Hyunjin Kim, Jin Hyup Lee, Jeen-Woo Park
Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in the general population and can evolve into nonalcoholic steatohepatosis (NASH), cirrhosis, and complications such as liver failure and hepatocellular carcinoma. Recently, we reported that mitochondrial NADP(+)-dependent isocitrate dehydrogenase, encoded by the IDH2, plays an important role in the regulation of redox balance and oxidative stress levels, which are tightly associated with intermediary metabolism and energy production. In the present study, we showed that in mice targeted disruption of IDH2 attenuates age-associated hepatic steatosis by the activation of p38/cJun NH2-terminal kinase (JNK) and p53, presumably induced by the elevation of mitochondrial reactive oxygen species (ROS), which in turn resulted in the suppression of hepatic lipogenesis and inflammation via the upregulation of fibroblast growth factor 21 (FGF21) and the inhibition of NFκB signaling pathways...
May 5, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28411440/tweak-fn14-promotes-pro-inflammatory-cytokine-secretion-in-hepatic-stellate-cells-via-nf-%C3%AE%C2%BAb-stat3-pathways
#19
Aixiu Wang, Feng Zhang, Hui Xu, Mingcui Xu, Yu Cao, Chen Wang, Yuanyuan Xu, Min Su, Ming Zhang, Yuzheng Zhuge
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) have been associated with liver disease. Hepatic stellate cells (HSCs) play a critical role in the hepatic wound-healing response after liver injury, but there is little information available on the role of the TWEAK/Fn14 pathway in human HSCs. In this study, we explored the role of TWEAK/Fn14 in activated human HSCs. The LX-2 cells were treated with TWEAK, and the expression of pro-inflammatory cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR)...
July 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28358987/highly-selective-targeting-of-hepatic-stellate-cells-for-liver-fibrosis-treatment-using-a-d-enantiomeric-peptide-ligand-of-fn14-identified-by-mirror-image-mrna-display
#20
Luying Huang, Jing Xie, Qiuyan Bi, Zhuoxuan Li, Sha Liu, Qing Shen, Chong Li
Although liver fibrosis is a major public health issue, there is still no effective drug therapy in the clinic. Fibroblast growth factor-inducible 14 (Fn14), a membrane receptor highly specifically expressed in activated hepatic stellate cells (HSCs), is the key driver of liver fibrosis, and thus, it has a great potential as a novel target for the development of effective treatment. Here, we identified a d-enantiomeric peptide ligand of Fn14 through mirror-image mRNA display. This included the chemical synthesis of a d-enantiomer of the target protein (extracellular domain of Fn14), identification of an l-peptide ligand of d-Fn14 using a constructed mRNA peptide library, and identification of a d-enantiomer of the l-peptide, which is a ligand of the natural Fn14 for reasons of symmetry...
April 12, 2017: Molecular Pharmaceutics
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