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fibroblast growth factor liver disease

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https://www.readbyqxmd.com/read/27919710/the-transcription-factor-carbohydrate-response-element-binding-protein-chrebp-a-possible-link-between-metabolic-disease-and-cancer
#1
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...
December 2, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27917437/nicotine-plus-a-high-fat-diet-triggers-cardiomyocyte-apoptosis
#2
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
#3
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
#4
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
#5
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: Non-alcoholic 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 may induce insulin resistance. We investigated the effects of diets high in animal protein vs plant protein, which differ in levels of methionine and BCAA, in subjects 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...
October 17, 2016: 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
#6
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
#7
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
#8
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...
September 19, 2016: Gut
https://www.readbyqxmd.com/read/27631137/the-suppression-of-hepatic-glucose-production-improves-metabolism-and-insulin-sensitivity-in-subcutaneous-adipose-tissue-in-mice
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27521506/new-pharmacologic-agents-that-target-inflammation-and-fibrosis-in-nonalcoholic-steatohepatitis-related-kidney-disease
#12
Giovanni Musso, Franco De Michieli, Daria Bongiovanni, Renato Parente, Luciana Framarin, Nicola Leone, Mara Berrutti, Roberto Gambino, Maurizio Cassader, Solomon Cohney, Elena Paschetta
Epidemiologic data show an association between the prevalence and severity of nonalcoholic fatty liver disease and the incidence and stage of chronic kidney disease (CKD); furthermore, nonalcoholic steatohepatitis (NASH)-related cirrhosis has a higher risk of renal failure, a greater necessity for simultaneous liver-kidney transplantation, and a poorer renal outcome than cirrhosis of other etiologies even after simultaneous liver-kidney transplantation. These data suggest that NASH and CKD share common proinflammatory and profibrotic mechanisms of progression, which are targeted incompletely by current treatments...
August 10, 2016: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27470139/fibroblast-growth-factor-21-reflects-liver-fat-accumulation-and-dysregulation-of-signalling-pathways-in-the-liver-of-c57bl-6j-mice
#13
Fenni Rusli, Joris Deelen, Evi Andriyani, Mark V Boekschoten, Carolien Lute, Erik B van den Akker, Michael Müller, Marian Beekman, Wilma T Steegenga
Fibroblast growth factor 21 (Fgf21) has emerged as a potential plasma marker to diagnose non-alcoholic fatty liver disease (NAFLD). To study the molecular processes underlying the association of plasma Fgf21 with NAFLD, we explored the liver transcriptome data of a mild NAFLD model of aging C57BL/6J mice at 12, 24, and 28 months of age. The plasma Fgf21 level significantly correlated with intrahepatic triglyceride content. At the molecular level, elevated plasma Fgf21 levels were associated with dysregulated metabolic and cancer-related pathways...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27462066/two-case-reports-of-fgf23-induced-hypophosphatemia-in-childhood-biliary-atresia
#14
Halley Wasserman, Chijioke Ikomi, Einar T Hafberg, Alexander G Miethke, Kevin E Bove, Philippe F Backeljauw
Cholestatic liver disease has long been associated with childhood rickets, secondary to impaired absorption of fat-soluble vitamin D. Elevated serum levels of fibroblast growth factor 23 (FGF23), secondary to genetic defects or tumor-induced osteomalacia, causes hypophosphatemic rickets in childhood. We present 2 infants with end-stage liver disease due to biliary atresia (BA) who developed hypophosphatemia with renal phosphate wasting. Serum FGF23 levels were elevated more than 8 times the upper limit of normal, and the older infant showed radiographic evidence of rickets...
August 2016: Pediatrics
https://www.readbyqxmd.com/read/27435856/fgf21-ameliorates-nonalcoholic-fatty-liver-disease-by-inducing-autophagy
#15
Shenglong Zhu, Yunzhou Wu, Xianlong Ye, Lei Ma, Jianying Qi, Dan Yu, Yuquan Wei, Guangxiao Lin, Guiping Ren, Deshan Li
The aim of this study is to evaluate the role of fibroblast growth factor 21 (FGF21) in nonalcoholic fatty liver disease (NAFLD) and seek to determine if its therapeutic effect is through induction of autophagy. In this research, Monosodium L-glutamate (MSG)-induced obese mice or normal lean mice were treated with vehicle, Fenofibrate, and recombinant murine FGF21, respectively. After 5 weeks of treatment, metabolic parameters including body weight, blood glucose and lipid levels, hepatic and fat gene expression levels were monitored and analyzed...
September 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27429519/differentiation-of-bone-marrow-derived-mesenchymal-stem-cells-into-hepatocyte-like-cells
#16
Nesrien M Al Ghrbawy, Reham Abdel Aleem Mohamed Afify, Nehal Dyaa, Asmaa A El Sayed
Cirrhosis is the end-stage liver fibrosis, whereby normal liver architecture is disrupted by fibrotic bands, parenchymal nodules and vascular distortion. Portal hypertension and hepatocyte dysfunction are the end results and give rise to major systemic complications and premature death. Mesenchymal stem cells (MSC) have the capacity of self-renew and to give rise to cells of various lineages, so MSC can be isolated from bone marrow (BM) and induced to differentiate into hepatocyte-like cells. MSC were induced to differentiate into hepatocyte-like cells by hepatotic growth factor (HGF) and fibroblast growth factor-4 (FGF-4)...
September 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/27427417/the-detrimental-role-played-by-lipocalin-2-in-alcoholic-fatty-liver-in-mice
#17
Yan Cai, Alvin Jogasuria, Huquan Yin, Ming-Jiang Xu, Xudong Hu, Jiayou Wang, Chunki Kim, Jiashin Wu, Kwangwon Lee, Bin Gao, Min You
We have previously shown that the ethanol-mediated elevation of lipocaline-2 (LCN2) is closely associated with the development of alcoholic fatty liver disease (AFLD) in mice. Herein, we aimed to understand the functional significance of LCN2 induction by ethanol and to explore its underlying mechanisms. We evaluated the effects of LCN2 in an in vitro cellular alcoholic steatosis model and in an animal study using wild-type and LCN2 knockout mice fed for 4 weeks with an ethanol-supplemented Lieber-DeCarli diet...
September 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27379400/generation-of-functional-hepatocyte-like-cells-from-human-deciduous-periodontal-ligament-stem-cells
#18
Punitha Vasanthan, Pukana Jayaraman, Wijenthiran Kunasekaran, Anthony Lawrence, Nareshwaran Gnanasegaran, Vijayendran Govindasamy, Sabri Musa, Noor Hayaty Abu Kasim
Human deciduous periodontal ligament stem cells have been introduced for as an easily accessible source of stem cells from dental origin. Although recent studies have revealed the ability of these stem cells in multipotential attribute, their efficiency of hepatic lineage differentiation has not been addressed so far. The aim of this study is to investigate hepatic lineage fate competence of periodontal ligament stem cells through direct media induction. Differentiation of periodontal ligament stem cells into hepatocyte-like cells was conducted by the exposure of two phase media induction...
August 2016: Die Naturwissenschaften
https://www.readbyqxmd.com/read/27293995/lack-of-fibroblast-growth-factor-21-accelerates-metabolic-liver-injury-characterized-by-steatohepatities-in-mice
#19
Xingkai Liu, Ping Zhang, Robert C Martin, Guozhen Cui, Guangyi Wang, Yi Tan, Lu Cai, Guoyue Lv, Yan Li
Fibroblast growth factor 21 (FGF21) concentrations are increased in human subjects who either have type 2 diabetes or nonalcoholic fatty liver disease (NAFLD). While excessive fat in the liver promotes the release of pro-inflammatory cytokines, NAFLD progresses from steatosis to non alcoholic steatohepatitis (NASH), a more aggressive form of hepatic damage, and lastly toward cirrhosis and HCC. In our previous study, loss of FGF21 is associated with hyper-proliferation, aberrant p53, and HCC development in diabetes mice...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27262842/hepatokines-and-non-alcoholic-fatty-liver-disease
#20
Dariusz M Lebensztejn, Marta Flisiak-Jackiewicz, Irena Białokoz-Kalinowska, Anna Bobrus-Chociej, Irina Kowalska
Nowadays non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver pathology both in adults and children. NAFLD manifestation ranges from a simple liver steatosis to steatohepatitis (nonalcoholic steatohepatitis - NASH), which may progress to advanced fibrosis, cirrhosis and end-stage liver disease. Due to the coexistence of visceral obesity, insulin resistance and dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome. In recent years, in the pathogenesis of metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and also NAFLD, more and more attention has been paid to the so-called organokines, proteins with both paracrine or/and endocrine activities...
2016: Acta Biochimica Polonica
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