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https://www.readbyqxmd.com/read/28430653/preventive-effects-of-the-sodium-glucose-cotransporter-2-inhibitor-tofogliflozin-on-diethylnitrosamine-induced-liver-tumorigenesis-in-obese-and-diabetic-mice
#1
Koki Obara, Yohei Shirakami, Akinori Maruta, Takayasu Ideta, Tsuneyuki Miyazaki, Takahiro Kochi, Hiroyasu Sakai, Takuji Tanaka, Mitsuru Seishima, Masahito Shimizu
Sodium glucose cotransporter 2 inhibitors are expected to ameliorate the abnormalities associated with metabolic syndrome including non-alcoholic fatty liver disease. In this study, we investigated the effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on the development of non-alcoholic fatty liver disease-related liver tumorigenesis in C57BL/KsJ-+Leprdb/+Leprdb obese and diabetic mice. The direct effects of tofogliflozin on human liver cancer cell proliferation were also evaluated. Mice were administered diethylnitrosamine-containing water for 2 weeks and were treated with tofogliflozin throughout the experiment...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430371/evaluation-of-circulating-zonulin-as-a-potential-marker-in-the-pathogenesis-of-nonalcoholic-fatty-liver-disease
#2
Olfat M Hendy, Maha M Elsabaawy, Mona M Aref, Fatma M Khalaf, Abdel Moaty A Oda, Helmy M El Shazly
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders ranging from simple hepatic steatosis up to nonalcoholic steatohepatitis (NASH) evolving to cirrhosis and hepatocellular carcinoma (HCC). Liver biopsy is still the gold standard modality for diagnosing and staging NAFLD. The linkage between intestinal microbiota and NAFLD, might suggest a potential role of serum zonulin in NAFLD diagnosis. To appraise the role of circulating zonulin in NAFLD pathogenesis, 56 subjects with proved NAFLD by ultrasonography and liver biopsy, as well as 20 healthy controls were tested...
April 21, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28429344/up-regulation-of-microrna-367-promotes-liver-steatosis-through-repressing-tbl1-in-obese-mice
#3
D-D Li, Y Liu, L Xue, D-Y Su, W-Y Pang
OBJECTIVE: Increasing evidence has demonstrated that microRNAs (miRNAs) play a critical role in the progression of metabolic disorders, including obesity-induced non-alcoholic fatty liver disease (NAFLD). In the present study, the expression and function of miR-367 were investigated. MATERIALS AND METHODS: C57BL/6 male mice aged 8 weeks were fed with a normal diet (ND) or high-fat-diet (HFD). The expression levels of miR-367 were analyzed in livers from two groups of mice by quantitative real-time PCR...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28428634/lipid-droplets-and-liver-disease-from-basic-biology-to-clinical-implications
#4
REVIEW
Nina L Gluchowski, Michel Becuwe, Tobias C Walther, Robert V Farese
Lipid droplets are dynamic organelles that store neutral lipids during times of energy excess and serve as an energy reservoir during deprivation. Many prevalent metabolic diseases, such as the metabolic syndrome or obesity, often result in abnormal lipid accumulation in lipid droplets in the liver, also called hepatic steatosis. Obesity-related steatosis, or NAFLD in particular, is a major public health concern worldwide and is frequently associated with insulin resistance and type 2 diabetes mellitus. Here, we review the latest insights into the biology of lipid droplets and their role in maintaining lipid homeostasis in the liver...
April 21, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28428362/hepatic-lipid-accumulation-cause-and-consequence-of-dysregulated-glucoregulatory-hormones
#5
Caroline E Geisler, Benjamin Jennings Renquist
Fatty liver can be diet, endocrine, genetic, viral, or drug induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic, and ketogenic genes, promoting hyperglycemia, hyperlipidemia, and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency, and elevated sympathetic tone...
April 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28428350/targeted-inactivation-of-copper-transporter-atp7b-in-hepatocytes-causes-liver-steatosis-and-obesity-in-mice
#6
Abigael Muchenditsi, Haojun Yang, James P Hamilton, Lahari Koganti, Franck Housseau, Lisa Aronov, Hongni Fan, Hannah Pierson, Ashima Bhattacharjee, Robert C Murphy, Cynthia L Sears, James J Potter, Clavia Ruth Wooton-Kee, Svetlana Lutsenko
The copper transporter ATP7B is essential for mammalian copper homeostasis. Mutations in ATP7B result in copper accumulation, especially in the liver, and cause Wilson disease (WD). The major role of hepatocytes in WD pathology is firmly established. It is less certain whether the excess Cu in hepatocytes is solely responsible for development of WD. To address this issue, we generated a mouse strain for Cre-mediated deletion of Atp7b and inactivated Atp7b selectively in hepatocytes. Atp7bΔ(Hep) mice accumulate copper in the liver, have elevated urinary copper, lack holo-ceruloplasmin, but show no liver disease for up to 30 weeks...
April 20, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28428116/cycloastragenol-improves-hepatic-steatosis-by-activating-farnesoid-x-receptor-signalling
#7
Ming Gu, Shiying Zhang, Yuanyuan Zhao, Jinwen Huang, Yahui Wang, Yin Li, Shengjie Fan, Li Yang, Guang Ji, Qingchun Tong, Cheng Huang
Non-alcoholic fatty liver disease (NAFLD) has become a global health problem. However, there is no approved therapy for NAFLD. Farnesoid X receptor (FXR) is a potential drug target for treatment of NAFLD. In an attempt to screen FXR agonists, we found that cycloastragenol (CAG), a natural occurring compound in Astragali Radix, stimulated FXR transcription activity. In animal studies, we demonstrated that CAG treatment resulted in obvious reduction of high-fat diet induced lipid accumulation in liver accompanied by lowered blood glucose, serum triglyceride levels and hepatic bile acid pool size...
April 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28427497/mirtazapine-induced-steatosis%C3%A2
#8
Elin Thomas, Hasan Haboubi, Namor Williams, Aled Lloyd, Chin Lye Ch'ng
Mirtazapine is a commonly used drug indicated for the treatment of severe depression. It works as a presynaptic α2-adrenoreceptor antagonist that increases central noradrenergic and serotonergic neurotransmission, and it is metabolized by the p450 cytochrome oxidase system. There is evidence within the literature to suggest a link between antidepressants and increased liver enzymes, although case reports demonstrating a link between mirtazapine specifically and steatosis are sparse. Here, we present a case of mirtazapine-induced steatosis in a 48-year-old office worker...
April 21, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28426902/hepatic-steatosis-after-pediatric-liver-transplant
#9
Emily R Perito, Tabitha Vase, Rageshree Ramachandran, Andrew Phelps, Kuang-Yu Jen, Robert H Lustig, Vickie A Feldstein, Philip Rosenthal
RATIONALE: Hepatic steatosis develops after liver transplant in 30% of adults, and non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in non-transplanted children. However, post-transplant steatosis has been minimally studied in pediatric liver transplant recipients. We explored the prevalence, persistence, and association with chronic liver damage of hepatic steatosis in these children. RESULTS: In this single-center study of pediatric patients transplanted 1988-2015 (n=318), 31% of those with any post-transplant biopsy (n=271) had ≥1 biopsy with steatosis...
April 20, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28426815/using-controlled-attenuation-parameter-combined-with-ultrasound-to-survey-non-alcoholic-fatty-liver-disease-in-hemodialysis-patients-a-prospective-cohort-study
#10
Yi-Hao Yen, Jin-Bor Chen, Ben-Chung Cheng, Jung-Fu Chen, Kuo-Chin Chang, Po-Lin Tseng, Cheng-Kun Wu, Ming-Chao Tsai, Ming-Tsung Lin, Tsung-Hui Hu
BACKGROUND AND AIMS: Controlled attenuation parameter (CAP) is a non-invasive method for measuring hepatic steatosis (HS). Non-alcoholic fatty liver disease (NAFLD) is closely related to cardiovascular diseases (CVDs). CVDs are the leading cause of morbidity and mortality in hemodialysis patients. The aim of this study was to investigate the prevalence of NAFLD in hemodialysis patients. METHOD: We prospectively enrolled patients undergoing chronic hemodialysis, as well as patients with normal renal function who served as controls...
2017: PloS One
https://www.readbyqxmd.com/read/28425566/gender-specific-histopathological-response-in-guppies-poecilia-reticulata-exposed-to-glyphosate-or-its-metabolite-aminomethylphosphonic-acid
#11
Adriana Maria Antunes, Thiago Lopes Rocha, Fernando Santiago Pires, Meire Alves de Freitas, Vanessa Rafaela Milhomem Cruz Leite, Sarah Arana, Paulo César Moreira, Simone Maria Teixeira Sabóia-Morais
Ecotoxicity of glyphosate (GLY) and its metabolite aminomethylphosphonic acid (AMPA) was investigated in guppies, Poecilia reticulata. We tested the effects of these chemicals on the gills and liver of both male and female guppies using qualitative and quantitative histopathological analyses associated with histopathological condition indexes. Both genders showed similar median lethal concentration (LC50 ) at 96 h for GLY (68.78 and 70.87 mg l(-1) ) and AMPA (180 and 164.32 mg l(-1) ). However, the histopathological assessment of both fish organs exposed to sublethal concentrations of GLY (35 mg l(-1) ) and AMPA (82 mg l(-1) ) for 96 h showed a tissue- and gender-specific histopathological response...
April 20, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28424943/intestinal-alkaline-phosphatase-attenuates-alcohol-induced-hepatosteatosis-in-mice
#12
Sulaiman R Hamarneh, Byeong-Moo Kim, Kanakaraju Kaliannan, Sara A Morrison, Tyler J Tantillo, Qingsong Tao, Mussa M Rafat Mohamed, Juan M Ramirez, Aaron Karas, Wei Liu, Dong Hu, Abeba Teshager, Sarah Shireen Gul, Konstantinos P Economopoulos, Atul K Bhan, Madhu S Malo, Michael Y Choi, Richard A Hodin
BACKGROUND AND AIMS: Bacterially derived factors from the gut play a major role in the activation of inflammatory pathways in the liver and in the pathogenesis of alcoholic liver disease. The intestinal brush-border enzyme intestinal alkaline phosphatase (IAP) detoxifies a variety of bacterial pro-inflammatory factors and also functions to preserve gut barrier function. The aim of this study was to investigate whether oral IAP supplementation could protect against alcohol-induced liver disease...
April 19, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28424924/effects-of-gw002-a-novel-recombinant-human-glucagon-like-peptide-1-glp-1-analog-fusion-protein-on-cho-recombinant-cells-and-bks-db-mice
#13
Wan-Wan Ji, Dong-An Yu, Min Fan, Meng You, You Lu, Er-Bing Li, Ning Xie, Shou-Sheng Yan
AIMS: GLP-1-based strategies have many advantages in treatment of type 2 diabetes mellitus (T2DM), but native GLP-1 has a short half-life in the circulation, which limits its clinical application. The purpose of this study was to evaluate the effects of GW002, a novel recombinant GLP-1 analog fusion protein produced by linking the human GLP-1 analog C-terminus to the N-terminus of human serum albumin via a linker, in vitro and in BKS-db mice. METHODS: To determine whether GW002 can activate the GLP-1 receptor in cells, the level of luciferase expression was evaluated in vitro...
April 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28422962/docosahexaenoic-acid-blocks-progression-of-western-diet-induced-nonalcoholic-steatohepatitis-in-obese-ldlr-mice
#14
Kelli A Lytle, Carmen P Wong, Donald B Jump
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major public health concern in western societies. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is characterized by hepatic steatosis, inflammation, oxidative stress and fibrosis. NASH is a risk factor for cirrhosis and hepatocellular carcinoma. NASH is predicted to be the leading cause of liver transplants by 2020. Despite this growing public health concern, there remain no Food and Drug Administration (FDA) approved NASH treatments...
2017: PloS One
https://www.readbyqxmd.com/read/28422772/can-ultrasound-imaging-predict-the-success-of-an-experimental-steatofibrosis-model
#15
Rustu Turkay, Abdurrahman Fatih Aydin, Ilknur Bingul, Canan Kucukgergin, Isin Dogan-Ekici, Elif Hocaoglu, Ercan Inci, Baris Bakir, Mujdat Uysal
Our goal was to evaluate the role of ultrasound (US) imaging in an experimental 2-hit steatofibrosis rat model. Nineteen female Sprague-Dawley rats were divided into 2 groups: control group (n = 6) and high-fat diet carbontetrachloride (HFD-CCl4) group (n = 13) that was fed with HFD for 14 weeks. Ultrasound was performed to evaluate liver steatosis. The HFD-CCl4 group rats were divided further into 2 subgroups: HFD rats with liver steatosis [US (+) group; n = 6] and without steatosis [US (-) group; n = 7]. All rats in the subgroups were administered with CCl4...
April 19, 2017: Ultrasound Quarterly
https://www.readbyqxmd.com/read/28422749/obesity-induced-hepatic-steatosis-is-mediated-by-endoplasmic-reticulum-stress-in-the-subfornical-organ-of-the-brain
#16
Julie A Horwath, Chansol Hurr, Scott D Butler, Mallikarjun Guruju, Martin D Cassell, Allyn L Mark, Robin L Davisson, Colin N Young
Nonalcoholic fatty liver disease (NAFLD), characterized by an excess accumulation of hepatic triglycerides, is a growing health epidemic. While ER stress in the liver has been implicated in the development of NAFLD, the role of brain ER stress - which is emerging as a key contributor to a number of chronic diseases including obesity - in NAFLD remains unclear. These studies reveal that chemical induction of ER stress in the brain caused hepatomegaly and hepatic steatosis in mice. Conversely, pharmacological reductions in brain ER stress in diet-induced obese mice rescued NAFLD independent of body weight, food intake, and adiposity...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28422425/negativization-of-viremia-prior-to-liver-transplant-reduces-early-allograft-dysfunction-in-hepatitis-c-recipients
#17
Silvia Martini, Francesco Tandoi, Lodovico Terzi di Bergamo, Silvia Strona, Bruna Lavezzo, Marco Sacco, Francesca Maione, Federica Gonella, Paolo Strignano, Dominic Dell Olio, Mauro Salizzoni, Giorgio Maria Saracco, Renato Romagnoli
Although early allograft dysfunction (EAD) negatively impacts on survival from the first months following liver transplantation (LT), direct-acting antivirals (DAAs) have revolutionized HCV therapy. We investigated the EAD definition best predicting 90-day graft loss and identified EAD risk factors in HCV positive recipients. From 11-2002 to 06-2016, 603 HCV-positive patients (hepatocellular carcinoma 53.4%) underwent a first LT with HCV-negative donors. Median recipient MELD score 15, median donor age 63 years...
April 19, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28422289/dietary-tuna-dark-muscle-protein-attenuates-hepatic-steatosis-and-increases-serum-high-density-lipoprotein-cholesterol-in-obese-type-2-diabetic-obese-kk-a-y-mice
#18
Hayato Maeda, Ryota Hosomi, Mari Fukuda, Yuki Ikeda, Munehiro Yoshida, Kenji Fukunaga
Tuna muscle consists of light and dark muscle in approximately equal proportions. However, besides for the light muscle of tuna, cod, sardine, and salmon, few researches have assessed the health-promoting functions of fish protein. Therefore, we evaluated the mechanisms underlying the alteration of lipid storage and cholesterol metabolism following the intake of tuna dark muscle protein (TDMP) by obese type-2 diabetic/obese mice. Four-week-old male KK-A(y) mice were separated into 2 dietary groups, with one group receiving a casein-based diet and the other receiving a diet with the substitution of part of the protein (50%, w/w) by TDMP (TDMP diet) for 4 wk...
April 19, 2017: Journal of Food Science
https://www.readbyqxmd.com/read/28422172/transient-elastography-as-a-screening-tool-for-liver-fibrosis-in-a-large-hemodialysis-population
#19
Ben-Chung Cheng, Yi-Hao Yen, Jung-Fu Chen, Cheng-Kun Wu, Kuo-Chin Chang, Po-Lin Tseng, Ming-Chao Tsai, Ming-Tsung Lin, Jung-Ting Lin, Jin-Bor Chen, Tsung-Hui Hu
Metabolic syndrome, an etiological factor in non-alcoholic fatty liver disease (NAFLD), is often present in hemodialysis patients. Little is known about the prevalence of, and factors associated with, liver fibrosis in hemodialysis populations. We used transient elastography (TE) to investigate these phenomena. 659 patients treated with chronic hemodialysis were enrolled. We excluded those with excess alcohol intake, liver stiffness measurement (LSM) failure, or unreliable LSM values. LSM ≥8.0 kPa was used as a cutoff suggesting clinically relevant fibrosis...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28421320/hepatocyte-specific-depletion-of-ubiquitin-regulatory-x-domain-containing-protein-8-accelerates-fibrosis-in-a-mouse-non-alcoholic-steatohepatitis-model
#20
Norihiro Imai, Michitaka Suzuki, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Kazuhiko Hayashi, Masatoshi Ishigami, Yoshiki Hirooka, Tetsuya Ishikawa, Hidemi Goto, Toyoshi Fujimoto
Ubiquitin regulatory X domain-containing protein 8 (UBXD8) is engaged in the degradation of lipidated apolipoprotein B in hepatocytes. We previously showed that hepatocyte-specific UBXD8-deficient mice (U8-HKO) fed a moderately high-fat diet (31 kcal % fat) showed periportal macrovesicular steatosis along with a decrease in very low-density lipoprotein secretion, but did not develop fibrosis. In the present study, we examined whether U8-HKO mice show NASH-like phenotypes when fed a very high-fat diet (60 kcal % fat)...
April 18, 2017: Histochemistry and Cell Biology
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