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https://www.readbyqxmd.com/read/29673898/activation-of-liver-ampk-with-pf-06409577-corrects-nafld-and-lowers-cholesterol-in-rodent-and-primate-preclinical-models
#1
Ryan M Esquejo, Christopher T Salatto, Jake Delmore, Bina Albuquerque, Allan Reyes, Yuji Shi, Rob Moccia, Emily Cokorinos, Matthew Peloquin, Mara Monetti, Jason Barricklow, Eliza Bollinger, Brennan K Smith, Emily A Day, Chuong Nguyen, Kieran F Geoghegan, John M Kreeger, Alan Opsahl, Jessica Ward, Amit S Kalgutkar, David Tess, Lynne Butler, Norimitsu Shirai, Timothy F Osborne, Gregory R Steinberg, Morris J Birnbaum, Kimberly O Cameron, Russell A Miller
Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid accumulation and ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a treatment for metabolic diseases; we show that the AMPK β1-biased activator PF-06409577 is capable of lowering hepatic and systemic lipid and cholesterol levels in both rodent and monkey preclinical models...
April 8, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29673321/relationship-of-sarcopenia-with-steatohepatitis-and-advanced-liver-fibrosis-in-non-alcoholic-fatty-liver-disease-a-meta-analysis
#2
Rui Yu, Qiangwei Shi, Lei Liu, Lidong Chen
BACKGROUND: Several studies have emerged indicating that sarcopenia is associated with nonalcoholic fatty liver disease, we aimed to systematically review and quantify the association between sacropenia and the histological severity of nonalcoholic fatty liver disease. METHODS: Pubmed, the Cochrane Library and EMBASE were searched (until August 2017) for studies examining the relationship of sarcopenia with steatohepatitis and advanced liver fibrosis in nonalcoholic fatty liver disease...
April 19, 2018: BMC Gastroenterology
https://www.readbyqxmd.com/read/29670908/liver-x-receptor-inverse-agonist-sr9243-suppresses-nonalcoholic-steatohepatitis-intrahepatic-inflammation-and-fibrosis
#3
Peng Huang, Benson Kaluba, Xiao-Lin Jiang, Shi Chang, Xiao-Feng Tang, Lin-Feng Mao, Zhi-Peng Zhang, Fei-Zhou Huang
Abnormal metabolism of cholesterol may be a contributing factor in nonalcoholic steatohepatitis (NASH) pathogenesis. Accumulating evidence has shown that liver X receptor (LXR) is closely related to intrahepatic inflammation and fibrosis. In this study, we evaluated the effects of a novel liver-specific LXR inverse agonist, SR9243, on antifibrosis in NASH mice. A high-cholesterol diet was employed to induce NASH in BALB/c mice by either carbon tetrachloride (CCL4) administration or bile-duct ligation (BDL)...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29668871/transgenic-mice-overexpressing-srebp-1a-in-male-ob-ob-mice-exhibit-lipodystrophy-and-exacerbate-insulin-resistance
#4
Hiroshi Ohno, Takashi Matsuzaka, Nie Tang, Rahul Sharma, Kaori Motomura, Takuya Shimura, Aoi Satoh, Song-Iee Han, Yoshinori Takeuchi, Yuichi Aita, Hitoshi Iwasaki, Shigeru Yatoh, Hiroaki Suzuki, Motohiro Sekiya, Yoshimi Nakagawa, Hirohito Sone, Naoya Yahagi, Nobuhiro Yamada, Yoshikazu Higami, Hitoshi Shimano
Sterol regulatory element-binding protein-1a (SREBP-1a) is a key transcription factor which activates the expression of genes involved in the synthesis of fatty acids, triglycerides, and cholesterol. Transgenic mice that overexpress the nuclear form of SREBP-1a under the control of phosphoenolpyruvate carboxykinase (PEPCK) promoter (Tg-1a) were previously shown to display a lipodystrophic phenotype characterized by enlarged and fatty livers, diminished peripheral white adipose tissue (WAT), and insulin resistance...
April 12, 2018: Endocrinology
https://www.readbyqxmd.com/read/29666185/hepatocyte-nuclear-receptor-shp-suppresses-inflammation-and-fibrosis-in-a-mouse-model-of-nonalcoholic-steatohepatitis
#5
An Zou, Nancy Magee, Fengyan Deng, Sarah Lehn, Cuncong Zhong, Yuxia Zhang
Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide, ranging from nonalcoholic fatty liver (NAFL, steatosis without hepatocellular injury) to the more aggressive nonalcoholic steatohepatitis (NASH, steatosis with ballooning, inflammation, or fibrosis). Although many studies have greatly contributed to the elucidation of NAFLD pathogenesis, the disease progression from NAFL to NASH still remains incompletely understood. Nuclear receptor small heterodimer partner (Nr0b2, SHP) is a transcriptional regulator critical for the regulation of bile acid, glucose, and lipid metabolism...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29662454/the-biological-clock-a-pivotal-hub-in-non-alcoholic-fatty-liver-disease-pathogenesis
#6
REVIEW
Gianluigi Mazzoccoli, Salvatore De Cosmo, Tommaso Mazza
Non-alcoholic fatty liver disease (NAFLD) is the most frequent hepatic pathology in the Western world and may evolve into steatohepatitis (NASH), increasing the risk of cirrhosis, portal hypertension and hepatocellular carcinoma. NAFLD derives from the accumulation of hepatic fat due to discrepant free fatty acid metabolism. Other factors contributing to this are deranged nutrients and bile acids fluxes as well as alterations in nuclear receptors, hormones, and intermediary metabolites, which impact on signaling pathways involved in metabolism and inflammation...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29662288/nonalcoholic-fatty-liver-disease-and-liver-transplantation-where-do-we-stand
#7
REVIEW
Ivana Mikolasevic, Tajana Filipec-Kanizaj, Maja Mijic, Ivan Jakopcic, Sandra Milic, Irena Hrstic, Nikola Sobocan, Davor Stimac, Patrizia Burra
Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation (LT), on patients on the waiting list for transplant, on post-transplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT...
April 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29661561/clinically-actionable-hypercholesterolemia-and-hypertriglyceridemia-in-children-with-nonalcoholic-fatty-liver-disease
#8
Kathryn E Harlow, Jonathan A Africa, Alan Wells, Patricia H Belt, Cynthia A Behling, Ajay K Jain, Jean P Molleston, Kimberly P Newton, Philip Rosenthal, Miriam B Vos, Stavra A Xanthakos, Joel E Lavine, Jeffrey B Schwimmer
OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network...
April 13, 2018: Journal of Pediatrics
https://www.readbyqxmd.com/read/29661431/stratifying-mortality-in-a-model-for-end-stage-liver-disease-waiting-list-a-brazilian-single-center-study
#9
R B Martino, D R Waisberg, A P M Dias, V B S Inoue, R M Arantes, L B P Haddad, W Andraus, L D Lopes, F H F Galvão, A T W Song, L A C D'Albuquerque
BACKGROUND: The Model for End-Stage Liver Disease (MELD) system reliably predicts mortality in cirrhotic patients. However, the etiology of liver disease and presence of portal vein thrombosis are not directly taken into account in MELD score. Its impact on the outcomes of patients on the waiting list is still unclear. The aim of this study was to investigate mortality and access to transplantation regarding etiology of liver disease and portal vein thrombosis (PVT). METHODS: A total of 465 adult patients on the liver waiting list from August 2015 to August 2016 were followed up until August 2017...
April 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29660603/both-alcoholic-and-non-alcoholic-steatohepatitis-association-with-cardiovascular-risk-and-liver-fibrosis
#10
Beatriz A Sánchez-Jiménez, Diana Brizuela-Alcántara, Martha H Ramos-Ostos, Luis F Alva-López, Misael Uribe-Esquivel, Norberto C Chávez-Tapia
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. Mortality in NAFLD is mainly related to cardiovascular disease (CVD) and cancer. NAFLD and its association with both CVD and liver disease risk have been well evaluated, but the association of NAFLD with alcohol, known as "both alcoholic and non-alcoholic steatohepatitis" (BASH), remains uncertain. The objective of this study was to assess the influence of alcohol and obesity in the development of liver and cardiovascular disease risk...
November 15, 2017: Alcohol
https://www.readbyqxmd.com/read/29656250/exposure-to-environmental-level-phenanthrene-induces-a-nash-like-phenotype-in-new-born-rat
#11
Jiaojiao Guo, Chonggang Wang, Zhizhun Guo, Zhenghong Zuo
More and more evidence indicates that persistent organic pollutants (POPs) are a risk factor for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Phenanthrene (Phe) is a kind of POP which existed extensively in the environment, but whose toxicity on mammals has so far received less focus. Subcutaneously injection of Phe (0.5, 5, 50 μg/kg) for 21 days induced significant NAFLD/NASH symptoms in new born rats. Exposure to environmental levels of Phe decreased body weight and liver-somatic index; impaired histology of liver; influenced the peroxisome proliferator-activated receptor gamma (PPARγ) signaling and lipid metabolism in liver; stimulated oxidative stress in the rats' liver; induced the variation of NFκB pathway and liver inflammatory response; and caused liver fibrosis via transforming growth factor β1 (tgfβ1)...
April 12, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29656147/liver-fibrosis-direct-antifibrotic-agents-and-targeted-therapies
#12
REVIEW
Detlef Schuppan, Muhammad Ashfaq-Khan, Ai Ting Yang, Yong Ook Kim
Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C. Highly effective antiviral therapy can prevent progression or even induce reversal in the majority of patients, but such treatment remains elusive for the majority of liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic or autoimmune liver diseases...
April 12, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29653253/cholesterol-and-bile-acid-mediated-regulation-of-autophagy-in-fatty-liver-diseases-and-atherosclerosis
#13
REVIEW
Yifeng Wang, Wen-Xing Ding, Tiangang Li
Liver is the major organ that regulates whole body cholesterol metabolism. Disrupted hepatic cholesterol homeostasis contributes to the pathogenesis of nonalcoholic steatohepatitis, dyslipidemia, atherosclerosis, and cardiovascular diseases. Hepatic bile acid synthesis is the major catabolic mechanism for cholesterol elimination from the body. Furthermore, bile acids are signaling molecules that regulate liver metabolism and inflammation. Autophagy is a highly-conserved lysosomal degradation mechanism, which plays an essential role in maintaining cellular integrity and energy homeostasis...
April 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29651702/tsumura-suzuki-obese-diabetic-mice-derived-hepatic-tumors-closely-resemble-human-hepatocellular-carcinomas-in-metabolism-related-genes-expression-and-bile-acid-accumulation
#14
Tetsuyuki Takahashi, Ulrich Deuschle, Shu Taira, Takeshi Nishida, Makoto Fujimoto, Takao Hijikata, Koichi Tsuneyama
BACKGROUND AND AIMS: Tsumura-Suzuki obese diabetic (TSOD) is a good model of metabolic syndrome showing typical lesions found in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and develops spontaneous hepatic tumors with a high frequency. Majority of the developing tumors overexpress glutamine synthetase (GS), which is used as a marker of hepatocellular carcinoma (HCC). The aim of this study is to assess the status of expression of metabolism-related genes and the level of bile acids in the TSOD mice-derived tumors and to determine the association with metabolic dysregulation between human HCC and TSOD mice-derived tumors...
April 12, 2018: Hepatology International
https://www.readbyqxmd.com/read/29643297/investigation-of-pharmacological-responses-to-anti-diabetic-drugs-in-female-spontaneously-diabetic-torii-sdt-fatty-rats-a-new-nonalcoholic-steatohepatitis-nash-model
#15
Yasufumi Toriniwa, Tomoyuki Saito, Katsuhiro Miyajima, Yukihito Ishii, Kinuko Uno, Tatsuya Maekawa, Tohru Matsui, Shinichi Kume, Takahisa Yamada, Takeshi Ohta
Nonalcoholic steatohepatitis (NASH) is a progressive liver disease, and some patients develop hepatic cirrhosis/carcinoma. Animal models play key roles in the development of new therapies for NASH. In this study, the pharmacological effects of metformin and pioglitazone were investigated in female Spontaneously Diabetic Torii (SDT) fatty rats to verify the utility of this model. The anti-diabetic drugs were administered to SDT fatty rats fed a cholesterol-enriched diet from 4 to 25 weeks, and changes in food intake, body weight, and blood chemistry parameters were evaluated every 4 weeks...
April 10, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29629906/low-rates-of-retention-into-hepatocellular-carcinoma-hcc-surveillance-program-after-initial-hcc-screening
#16
Ann Robinson, Hesam Tavakoli, Ramsey Cheung, Benny Liu, Taft Bhuket, Robert J Wong
GOALS: To evaluate rates and predictors of retention into hepatocellular carcinoma (HCC) surveillance beyond initial screening among underserved cirrhosis patients. BACKGROUND: Although initial HCC screening among cirrhosis patients remains low, few studies have evaluated retention to HCC surveillance beyond initial screening. METHODS: We retrospectively evaluated all consecutive adults with cirrhosis from 2014 to 2017 at a single underserved safety net hospital system to determine rates of HCC surveillance at 6 months and at 1 year beyond initial screening...
April 6, 2018: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/29627620/efficacy-safety-and-tolerability-of-lubiprostone-for-the-treatment-of-non-alcoholic-fatty-liver-disease-in-adult-patients-with-constipation-the-lubiprone-double-blind-randomised-placebo-controlled-study-design
#17
Takaomi Kessoku, Kento Imajo, Takashi Kobayashi, Yasushi Honda, Takayuki Kato, Yuji Ogawa, Wataru Tomeno, Shingo Kato, Takuma Higurashi, Masato Yoneda, Hiroyuki Kirikoshi, Kazuki Kubota, Masataka Taguri, Takeharu Yamanaka, Haruki Usuda, Koichiro Wada, Satoru Saito, Atsushi Nakajima
BACKGROUND: This paper reports the protocol of a randomised, double-blind, placebo-controlled study to test the efficacy, safety, and tolerability of lubiprostone (LUB) vs. placebo on suppressing gut permeability in non-alcoholic fatty liver disease (NAFLD) patients with constipation. NAFLD, including non-alcoholic steatohepatitis (NASH), is a common chronic liver disorder. Progression is associated with increased gut permeability and gut-derived endotoxins. Most NAFLD/NASH clinical trial drugs aim to improve liver function or systemic metabolism...
April 5, 2018: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/29624631/temporal-trends-in-disease-presentation-and-survival-of-patients-with-hepatocellular-carcinoma-a-real-world-experience-from-1998-to-2015
#18
Nathan G Kim, Pauline P Nguyen, Hansen Dang, Radhika Kumari, Gabriel Garcia, Carlos O Esquivel, Mindie H Nguyen
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the few cancers whose incidence continues to increase. The goal of the current study was to investigate the presentation and survival trends of patients with HCC presenting to a university hospital between 1998 and 2015. METHODS: Study data were ascertained by individual chart review with survival data also supplemented by National Death Index query up to December 31, 2015. Patients were divided into three 6-year groups by diagnosis date (1998-2003, 2004-2009, and 2010-2015)...
April 6, 2018: Cancer
https://www.readbyqxmd.com/read/29619419/tumor-necrosis-factor-%C3%AE-mediated-hepatocyte-apoptosis-stimulates-fibrosis-in-the-steatotic-liver-in-mice
#19
Yosuke Osawa, Ekumi Kojika, Yukiko Hayashi, Masamichi Kimura, Koji Nishikawa, Sachiyo Yoshio, Hiroyoshi Doi, Tatsuya Kanto, Kiminori Kimura
Hepatocyte apoptosis has been implicated in the progression of nonalcoholic steatohepatitis. However, it is unclear whether the induction of tumor necrosis factor (TNF)-α-mediated hepatocyte apoptosis in the simple fatty liver triggers liver fibrosis. To address this question, high-fat diet-fed mice were repeatedly administered D-galactosamine, which increases the sensitivity of hepatocytes to TNF-α-mediated apoptosis. In mice treated with a high-fat diet plus D-galactosamine, hepatocyte apoptosis and liver fibrosis were induced, whereas both apoptosis and fibrosis were inhibited in these mice following gut sterilization with antimicrobials or knockout of TNF-α...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29619418/the-role-of-intestinal-c-type-regenerating-islet-derived-3-lectins-for-nonalcoholic-steatohepatitis
#20
Sena Bluemel, Lirui Wang, Cameron Martino, Suhan Lee, Yanhan Wang, Brandon Williams, Angela Horvath, Vanessa Stadlbauer, Karsten Zengler, Bernd Schnabl
C-type regenerating islet derived-3 (Reg3) lectins defend against pathogens and keep commensal bacteria at a distance. Deficiency of Reg3g and Reg3b facilitates alcohol-induced bacterial translocation and alcoholic liver disease. Intestinal Reg3g is down-regulated in animal models of diet-induced obesity, but the functional consequences for nonalcoholic steatohepatitis (NASH) are unknown. The aim of this study was to investigate the role of Reg3 lectins in NASH. NASH was induced by a Western-style fast-food diet in mice deficient for Reg3g or Reg3b and in transgenic mice overexpressing Reg3g in intestinal epithelial cells ( Reg3g Tg)...
April 2018: Hepatology Communications
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