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https://www.readbyqxmd.com/read/29782848/impaired-tfeb-mediated-lysosome-biogenesis-and-autophagy-promote-chronic-ethanol-induced-liver-injury-and-steatosis-in-mice
#1
Xiaojuan Chao, Shaogui Wang, Katrina Zhao, Yuan Li, Jessica A Williams, Tiangang Li, Hemantkumar Chavan, Partha Krishnamurthy, Xi C He, Linheng Li, Andrea Ballabio, Hong-Min Ni, Wen-Xing Ding
BACKGROUND & AIMS: Defects in lysosome function and autophagy contribute to pathogenesis of alcoholic liver disease. We investigated the mechanisms by which alcohol consumption affects these processes, evaluating the functions transcription factor EB (TFEB), which regulates lysosomal biogenesis. METHODS: We performed studies with GFP-LC3 mice, mice with liver-specific deletion of transcription factor EB (TFEB), mice with disruption of the transcription factor E3 gene (TFE3-knockout mice), mice with disruption of the Tefb and Tfe3 genes (TFEB, TFE3 double-knockout mice), and Tfebflox/flox albumin cre-negative mice (controls)...
May 18, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29779826/the-bckdh-kinase-and-phosphatase-integrate-bcaa-and-lipid-metabolism-via-regulation-of-atp-citrate-lyase
#2
Phillip J White, Robert W McGarrah, Paul A Grimsrud, Shih-Chia Tso, Wen-Hsuan Yang, Jonathan M Haldeman, Thomas Grenier-Larouche, Jie An, Amanda L Lapworth, Inna Astapova, Sarah A Hannou, Tabitha George, Michelle Arlotto, Lyra B Olson, Michelle Lai, Guo-Fang Zhang, Olga Ilkayeva, Mark A Herman, R Max Wynn, David T Chuang, Christopher B Newgard
Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulates branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis, and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K...
May 11, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29779697/usefulness-of-controlled-attenuation-parameter-for-detecting-increased-arterial-stiffness-in-general-population
#3
Hyo Eun Park, Heesun Lee, Su-Yeon Choi, Min-Sun Kwak, Jong In Yang, Jeong Yoon Yim, Goh Eun Chung
BACKGROUND: Liver fibroscan has recently been suggested as an alternative method to measure liver steatosis noninvasively. In this study, we evaluated usefulness of controlled attenuation parameter (CAP) for detecting increased arterial stiffness in general population. METHODS: A total of 515 asymptomatic patients without potential cause of liver disease who had liver fibroscan and cardio-ankle vascular index (CAVI) during their health check-up exams were included...
May 4, 2018: Digestive and Liver Disease
https://www.readbyqxmd.com/read/29779170/histological-improvement-of-non-alcoholic-steatohepatitis-with-a-prebiotic-a-pilot-clinical-trial
#4
Marc R Bomhof, Jill A Parnell, Hena R Ramay, Pam Crotty, Kevin P Rioux, Chris S Probert, Saumya Jayakumar, Maitreyi Raman, Raylene A Reimer
PURPOSE: In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted...
May 19, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29778510/assessment-of-intestinal-failure-associated-liver-disease-according-to-different-diagnostic-criteria
#5
Anna Simona Sasdelli, Federica Agostini, Caterina Pazzeschi, Mariacristina Guidetti, Simon Lal, Loris Pironi
BACKGROUND & AIMS: Intestinal failure associated liver disease (IFALD) has been defined using numerous criteria; however the clinical relevance of these criteria has never been compared. We therefore aimed to evaluate the prevalence, incidence, evolution of IFALD diagnosed by different criteria and to assess any clinical features that may be associated with its occurrence. METHODS: A cross sectional (CS) and retrospective study were carried out on adults on home parenteral nutrition (HPN) for chronic intestinal failure (CIF) managed at a single center...
May 8, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29777756/peroxiredoxin-5-regulates-adipogenesis-attenuating-oxidative-stress-in-obese-mouse-models-induced-by-a-high-fat-diet
#6
Mi Hye Kim, Sun-Ji Park, Jung-Hak Kim, Jung Bae Seong, Kyung-Min Kim, Hyun Ae Woo, Dong-Seok Lee
Elevated levels of reactive oxygen species (ROS) are a hallmark of obesity. Peroxiredoxin 5 (Prx5), which is a cysteine-dependent peroxidase enzyme, has an intensive ROS scavenging activity because it is located in the cytosol and mitochondria. Therefore, we focused on the role of Prx5 in regulating mitochondrial ROS and adipogenesis. We demonstrated that Prx5 expression was upregulated during adipogenesis and Prx5 overexpression suppressed adipogenesis by regulating cytosolic and mitochondrial ROS generation...
May 16, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29777706/n-3-polyunsaturated-fatty-acids-ameliorate-hepatic-steatosis-via-the-ppar-%C3%AE-cpt-1%C3%AE-pathway-in-a-mouse-model-of-parenteral-nutrition
#7
Feng Tian, Jiwei Wang, Haifeng Sun, Jianbo Yang, Peng Wang, Songlin Wan, Xuejin Gao, Li Zhang, Jieshou Li, Xinying Wang
Parenteral nutrition (PN) is one of the basic therapies for patients with intestinal failure; however, hepatic steatosis associated with PN limits the long-term use of PN. N-3 polyunsaturated fatty acids (PUFAs) have been used to improve clinical outcomes of patients receiving PN; however, the mechanisms by which n-3 PUFAs ameliorate hepatic steatosis remain unclear. In the present study, C57BL/6J mice were randomly assigned to three treatment groups, namely, enteral nutrition (EN), n-3 PUFAs, and n-6 PUFAs...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777704/dietary-mung-bean-protein-reduces-high-fat-diet-induced-weight-gain-by-modulating-host-bile-acid-metabolism-in-a-gut-microbiota-dependent-manner
#8
Akiho Nakatani, Xuan Li, Junki Miyamoto, Miki Igarashi, Hitoshi Watanabe, Asuka Sutou, Keita Watanabe, Takayasu Motoyama, Nobuhiko Tachibana, Mitsutaka Kohno, Hiroshi Inoue, Ikuo Kimura
The 8-globulin-rich mung bean protein (MPI) suppresses hepatic lipogenesis in rodent models and reduces fasting plasma glucose and insulin levels in obese adults. However, its effects on mitigating high fat diet (HFD)-induced obesity and the mechanism underlying these effects remain to be elucidated. Herein, we examined the metabolic phenotype, intestinal bile acid (BA) pool, and gut microbiota of conventionally raised (CONV-R) male C57BL/6 mice and germ-free (GF) mice that were randomized to receive either regular HFD or HFD containing mung bean protein isolate (MPI) instead of the dairy protein present in regular HFD...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777191/eradication-of-hepatitis-c-virus-is-associated-with-the-attenuation-of-steatosis-as-evaluated-using-a-controlled-attenuation-parameter
#9
Kohei Shimizu, Yoko Soroida, Masaya Sato, Hiromi Hikita, Tamaki Kobayashi, Momoe Endo, Mamiko Sato, Hiroaki Gotoh, Tomomi Iwai, Ryosuke Tateishi, Kazuhiko Koike, Yutaka Yatomi, Hitoshi Ikeda
Chronic hepatitis C virus (HCV) infection was shown to cause hepatic steatosis or suppression of serum lipid levels. However, little is known about the changes in hepatic steatosis following HCV eradication. We aimed to evaluate this issue using the controlled attenuation parameter (CAP), which was recently shown to provide a standardized non-invasive measure of hepatic steatosis. We enrolled 70 patients with chronic HCV infections and steatosis (CAP of over 248 dB/m) who had achieved a sustained viral response at 12 weeks after discontinuation of antiviral treatment using direct-acting antivirals (DAA)...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29775936/from-hit-to-lead-structure-based-discovery-of-naphthalene-1-sulfonamide-derivatives-as-potent-and-selective-inhibitors-of-fatty-acid-binding-protein-4
#10
Ding-Ding Gao, Hui-Xia Dou, Hai-Xia Su, Ming-Ming Zhang, Ting Wang, Qiu-Feng Liu, Hai-Yan Cai, Hai-Peng Ding, Zhuo Yang, Wei-Liang Zhu, Ye-Chun Xu, He-Yao Wang, Ying-Xia Li
Fatty acid binding protein 4 (FABP4) plays a critical role in metabolism and inflammatory processes and therefore is a potential therapeutic target for immunometabolic diseases such as diabetes and atherosclerosis. Herein, we reported the identification of naphthalene-1-sulfonamide derivatives as novel, potent and selective FABP4 inhibitors by applying a structure-based design strategy. The binding affinities of compounds 16dk, 16do and 16du to FABP4, at the molecular level, are equivalent to or even better than that of BMS309403...
May 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29774529/inhibition-of-prmt3-activity-selectively-impairs-lxr-driven-transcription-of-hepatic-lipogenic-genes-in-vivo
#11
Joya E Nahon, Christianne Groeneveldt, Janine J Geerling, Miranda Van Eck, Menno Hoekstra
BACKGROUND AND PURPOSE: Agonists for the liver X receptor (LXR) are considered promising therapeutic moieties in cholesterol-driven diseases by promoting cellular cholesterol efflux pathways. However, current clinical application of these agents is hampered by the concomitant LXR-induced activation of a lipogenic transcriptional network, leading to hepatic steatosis. Recent studies have suggested that protein arginine methyltransferase 3 (PRMT3) may act as a selective co-activator of LXR activity...
May 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29773823/comparison-of-conventional-sonographic-signs-and-magnetic-resonance-imaging-proton-density-fat-fraction-for-assessment-of-hepatic-steatosis
#12
Mimi Kim, Bo-Kyeong Kang, Dae Won Jun
This study correlated conventional ultrasonography (US) signs with the magnetic resonance imaging (MRI) proton density fat fraction (PDFF) to evaluate the diagnostic performance of US signs (alone or combined) to predict presence and degree of hepatic steatosis (HS). Overall, 182 subjects met the study inclusion criteria between February 2014 and October 2016. Four US signs were evaluated independently by two radiologists. MRI PDFF was defined as the average of 24 non-overlapping regions of interest (ROIs) within eight liver segments obtained by drawing three ROIs within each segment...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773653/inhibition-of-protein-arginine-methyltransferase-5-enhances-hepatic-mitochondrial-biogenesis
#13
Lei Huang, Jehnan Liu, Xiao-Ou Zhang, Katelyn Sibley, Sonia M Najjar, Mary M Lee, Joae Qiong Wu
Protein arginine methyltransferase 5 (PRMT5) regulates gene expression either transcriptionallyly by symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3, or at the post-translational level by methylation of non-histone target proteins. While emerging evidence suggests that PRMT5 functions as an oncogene, its role in metabolic diseases is not well defined. We investigated the role of PRMT5 in promoting high fat-induced hepatic steatosis. High fat diet up-regulated PRMT5 levels in the liver, but not in other metabolically relevant tissues such as skeletal muscle or white and brown adipose tissue...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29771124/genistein-ameliorates-non-alcoholic-fatty-liver-disease-by-targeting-thromboxane-a2-pathway
#14
Wenzhe Wang, Junliang Chen, Jinyan Mao, Hongling Li, Mingfu Wang, Hao Zhang, Haitao Li, Wei Chen
Non-alcoholic fatty liver disease (NAFLD) is now a public health issue worldwide, but no drug has received approval yet. Genistein, an isoflavonoid derived from soybean, ameliorates high fat diet-induced NAFLD in mice, but the molecular underpinnings remain largely elusive. Arachidonic acid is a major ingredient of animal fats, and arachidonic acid cascade has been implicated in chronic inflammation. In this study, we investigated whether genistein against NAFLD by targeting arachidonic acid cascade. By using a mouse model, we showed that genistein supplementation improved high-fat diet induced NAFLD by normalizing hepatomegaly, liver steatosis, aminotransferase abnormalities and glucose tolerance...
May 17, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29768729/adaptive-changes-in-pancreas-post-roux-en-y-gastric-bypass-induced-weight-loss
#15
A Lautenbach, M Wernecke, N Riedel, J Veigel, J Yamamura, S Keller, R Jung, P Busch, O Mann, F K Knop, J J Holst, J J Meier, J Aberle
AIMS: Obesity has been shown to trigger adaptive increases in pancreas parenchymal and fat volume. Consecutively, pancreatic steatosis may lead to beta-cell dysfunction. However, it is not known, whether the pancreatic tissue components decrease with weight loss and pancreatic steatosis is reversible following RYGB. Therefore, the objective of the study was to investigate the effects of RYGB-induced weight loss on pancreatic volume and glucose homeostasis. MATERIALS AND METHODS: 11 patients were recruited in the Obesity Centre of the University Medical Centre Hamburg-Eppendorf...
May 16, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29768686/prevalence-and-predictive-factors-of-moderate-severe-liver-steatosis-in-chronic-hepatitis-c-chc-infected-patients-evaluated-with-controlled-attenuation-parameter-cap
#16
Ana Carolina Cardoso, Renata M Perez, Claudio de Figueiredo-Mendes, Nathalie Carvalho Leite, Henrique Sergio Moraes Coelho, Cristiane A Villela-Nogueira
A novel controlled attenuation parameter (CAP) using FibroScan® has been developed for assessment of liver steatosis. The aim was to evaluate the frequency and associated factors for moderate/severe steatosis evaluated by CAP in CHC patients submitted to transient elastography (TE) by FibroScan® . CHC patients underwent TE with CAP evaluation. The classification of steatosis was defined as: CAP < 222 dB/m = S0; CAP ≥ 222 dB/m and <233dB /m = S1; ≥233 dB/m <290dB/m = S2 and >= 290 dB/m = S3...
May 16, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29768504/sarcopoterium-spinosum-extract-improved-insulin-sensitivity-in-mice-models-of-glucose-intolerance-and-diabetes
#17
Konstantin Rozenberg, Tovit Rosenzweig
BACKGROUND: The glucose lowering properties of Sarcopoterium spinosum, a traditional medicinal plant, were previously validated by us using KK-Ay mice as a genetic model for type 2 diabetes (T2D). OBJECTIVE: To clarify the effects of Sarcopoterium spinosum extract (SSE) on diet-induced glucose intolerance and to investigate SSE effects on carbohydrate and lipid metabolism in target tissues of both high-fat-diet (HFD)-fed and KK-Ay mice. RESULTS: Mice were given SSE (70 mg/day) for 6 weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29766802/endoplasmic-reticulum-stress-related-molecular-mechanisms-in-nonalcoholic-fatty-liver-disease-nafld
#18
Lifeng Wang, Jun Ren
Non-alcoholic fatty liver disease (NAFLD) has emerged as a common public health problem and a common cause of chronic liver diseases. However, the underlying mechanisms leading to the development and progression of NAFLD remain elusive. Accumulating evidence has depicted an essential role for endoplasmic reticulum (ER) stress in the development of steatosis and later progression into nonalcoholic steatohepatitis and hepatocarcinoma. With the accumulation of unfolded and misfolded proteins in the ER lumen, ER stress is provoked to turn on the unfolded protein response (UPR)...
May 16, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29765319/progression-and-regression-of-hepatic-lesions-in-a-mouse-model-of-nash-induced-by-dietary-intervention-and-its-implications-in-pharmacotherapy
#19
Zhi-Ming Ding, Yue Xiao, Xikun Wu, Haixia Zou, Shurong Yang, Yiyun Shen, Juehua Xu, Heather C Workman, Amy L Usborne, Haiqing Hua
Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH) is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765172/dietary-sucrose-regulates-the-expression-of-the-cd36-gene-in-hepatic-tissue-of-rats-with-obesity-and-non-alcoholic-fatty-liver-disease-nafld
#20
Rodolfo Quintana Castro, Ida Soto Rodriguez, Rosa A Deschamps Lago, Peter Grube Pagola, Jorge Rodriguez Antolin, Adriana Peres Quintal, Jaime Rivera Rivera, Alfonso Alexander Aguilera
AIM: To evaluate the mRNA expression levels of Cd36 in adipose and hepatic tissues, in rats with NAFLD after the consumption of sucrose for 10 and 20 weeks. METHODS: Twenty Wistar rats, all nearly 21 days old were divided into two experimental groups (NAFLD-10 and NAFLD-20), that received a standard diet (2014 Teklad Global) plus 30% sucrose in their drinking water for 10 and 20 weeks and the control groups (C Groups). Variables such as body weight, food intakes, and serum parameters were measured...
May 15, 2018: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
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