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https://www.readbyqxmd.com/read/29666185/hepatocyte-nuclear-receptor-shp-suppresses-inflammation-and-fibrosis-in-a-mouse-model-of-nonalcoholic-steatohepatitis
#1
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/29666152/phenylmethimazole-abrogates-diet-induced-inflammation-glucose-intolerance-and-nafld
#2
Ashley Patton, Tyler Church, Caroline Wilson, Jean Thuma, Douglas J Goetz, Darlene E Berryman, Edward O List, Frank L Schwartz, Kelly D McCall
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of both metabolic and inflammatory diseases and has become the leading chronic liver disease worldwide. High fat (HF) diets promote an increased uptake and storage of free fatty acids (FFAs) and triglycerides (TGs) in hepatocytes, which initiates steatosis and induces lipotoxicity, inflammation, and insulin resistance. Activation and signaling of Toll-like receptor 4 (TLR4) by FFAs induces inflammation evident in NAFLD and insulin resistance...
April 17, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29665034/metabolic-features-of-nonalcoholic-fatty-liver-nafl-in-obese-adolescents-findings-from-a-multi-ethnic-cohort
#3
Domenico Tricò, Sonia Caprio, Giuseppina Rosaria Umano, Bridget Pierpont, Jessica Nouws, Alfonso Galderisi, Grace Kim, Mariana M Mata, Nicola Santoro
AIMS: We conducted a prospective study in a large, multiethnic cohort of obese adolescents to characterize clinical and genetic features associated with pediatric Non-Alcoholic Fatty Liver (NAFL), the most common cause of chronic liver disease in youth. METHODS: A total of 503 obese adolescents were enrolled, including 191 (38.0%) Caucasians, 134 (26.6%) African Americans, and 178 (35.4%) Hispanics. Participants underwent abdominal magnetic resonance imaging (MRI) to quantify hepatic fat content, an oral glucose tolerance test to assess glucose tolerance and insulin sensitivity, and the genotyping of three SNPs associated with fatty liver (PNPLA3 rs738409, GCKR rs1260326, and TM6SF2 rs58542926)...
April 17, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29663608/the-effects-of-hexachloronaphthalene-on-selected-parameters-of-heme-biosynthesis-and-systemic-toxicity-in-female-wistar-rats-after-90-day-oral-exposure
#4
Michal Klimczak, Adam Darago, Elzbieta Bruchajzer, Katarzyna Domeradzka-Gajda, Maciej Stepnik, Katarzyna Kuzajska, Anna Kilanowicz
Hexachloronaphthalenes (HxCNs) are the most toxic congeners of polychlorinated naphthalenes, a group of compounds lately included into the list of persistent organic pollutants (POPs). This study presents the effects of 90-day intragastric administration of HxCN to female Wistar rats at doses of 0.03, 0.1, and 0.3 mg/kg body weight. The study examined selected parameters of the heme synthesis pathway, oxidative stress, hepatic cytochromes level, and basic hematology indicators. A micronucleus test was also performed...
April 16, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29663549/ostreolysin-induces-browning-of-adipocytes-and-ameliorates-hepatic-steatosis
#5
Lili Nimri, Katerina Staikin, Irena Peri, Einav Yehuda-Shnaidman, Betty Schwartz
BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is associated with all features of the metabolic syndrome. Deposition of excess triglycerides in liver cells, a hallmark of NAFLD, is associated with loss of insulin sensitivity. Ostreolysin (Oly) is a 15-kDa fungal protein known to interact with cholesterol-enriched raft-like membrane domains. We aim to test whether a recombinant version of Oly (rOly) can induce functional changes in vitro in adipocytes or in vivo in mice fed a high-fat diet (HFD)...
April 16, 2018: Journal of Gastroenterology and Hepatology
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/29662329/diagnosis-and-staging-of-fibrosis-in-patients-with-chronic-hepatitis-c-comparison-and-critical-overview-of-current-strategies
#7
REVIEW
Leandro César Mendes, Raquel Sb Stucchi, Aline G Vigani
In the past years, what has always been considered undisputed true in liver fibrosis staging has been challenged. Diagnostic performance of histological evaluation has proven to be significantly influenced by sample- and observer-related variabilities. Differentiation between lower levels of fibrosis remains difficult for many, if not all, test modalities, including liver biopsy but, perhaps, such a distinction is not indispensable in light of current therapeutic approaches. Biomarkers and elastography offer, nonetheless, high predictive values for advanced fibrosis and cirrhosis and correlate well with liver-related outcomes...
2018: Hepatic Medicine: Evidence and Research
https://www.readbyqxmd.com/read/29662288/nonalcoholic-fatty-liver-disease-and-liver-transplantation-where-do-we-stand
#8
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/29661433/better-selection-criteria-with-prognostic-factors-for-liver-transplantation
#9
L S Nacif, R S Pinheiro, V Rocha-Santos, V M Barbosa, A P de Moura Dias, R B Martino, R A Macedo, L Ducatti, L Haddad, F Galvão, W Andraus, L Carneiro D' Albuquerque
BACKGROUND: Liver transplantation has evolved significantly in recent years, with each advancement part of the effort toward increasing patient and graft survival as well as quality of life. The objective of this study was to evaluate the prognostic factors and selection criteria for liver transplantation. METHODS: Our study was a statistical analysis, logistic regression, and survival evaluation of a total of 80 liver transplants that were performed between June 1, 2016 and September 24, 2016...
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/29660324/magnetic-resonance-imaging-proton-density-fat-fraction-associates-with-progression-of-fibrosis-in-patients-with-nonalcoholic-fatty-liver-disease
#11
Veeral Ajmera, Charlie C Park, Cyrielle Caussy, Seema Singh, Carolyn Hernandez, Ricki Bettencourt, Jonathan Hooker, Ethan Sy, Cynthia Behling, Ronghui Xu, Michael S Middleton, Mark A Valasek, Claire Faulkner, Emily Rizo, Lisa Richards, Claude B Sirlin, Rohit Loomba
Markers are needed to predict progression of nonalcoholic fatty liver disease (NAFLD). The proton density fat fraction, measured by magnetic resonance imaging (MRI-PDFF), provides an accurate, validated marker of hepatic steatosis. However, it is not clear whether the proton density fat fraction identifies patients at risk for NAFLD progression. We performed a follow-up study of 95 well-characterized patients with biopsy-proven NAFLD and examined the association between liver fat content and fibrosis progression...
April 13, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29659970/cholic-acid-supplementation-of-a-high-fat-obesogenic-diet-suppresses-hepatic-triacylglycerol-accumulation-in-mice-via-a-fibroblast-growth-factor-21-dependent-mechanism
#12
Siri M Ippagunta, Alexei Kharitonenkov, Andrew C Adams, F Bradley Hillgartner
Background: Supplementation of a high-fat obesogenic diet (HFD) with cholic acid (CA) suppresses the development of obesity, insulin resistance, and hepatic steatosis in mice. Objective: We investigated the role of fibroblast growth factor 21 (FGF21) in mediating the beneficial actions of CA on metabolic syndrome. Methods: Male 7-wk-old wild-type (WT) mice and FGF21 knockout (FGF21KO) mice were fed an HFD for 12 wk followed by a 4-wk period in which the mice were fed the HFD alone or supplemented with 0...
April 1, 2018: Journal of Nutrition
https://www.readbyqxmd.com/read/29659785/glucocorticoid-induced-metabolic-disturbances-are-exacerbated-in-obese-male-mice
#13
Innocence Harvey, Erin J Stephenson, JeAnna R Redd, Quynh T Tran, Irit Hochberg, Nathan Qi, Dave Bridges
The purpose of this study was to determine the effects of glucocorticoid-induced metabolic dysfunction in the presence of diet-induced obesity. C57BL/6J adult male lean and diet-induced obese mice were given dexamethasone and levels of hepatic steatosis, insulin resistance and lipolysis were determined. Obese mice given dexamethasone had significant, synergistic effects on fasting glucose, insulin resistance and markers of lipolysis, as well as hepatic steatosis. This was associated with synergistic transactivation of the lipolytic enzyme ATGL...
April 11, 2018: Endocrinology
https://www.readbyqxmd.com/read/29657020/helicobacter-pylori-infection-aggravates-diet-induced-nonalcoholic-fatty-liver-in-mice
#14
Cong He, Dandan Cheng, Huan Wang, Ketao Wu, Yin Zhu, Nonghua Lu
BACKGROUND: Previous epidemiological studies have suggested a link between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD), yet animal studies are lacking to elucidate this association. In this study, we evaluated the potential effects of H. pylori infection on NAFLD in mice. METHODS: We first established two strains of H. pylori infected mice model with either chow diet or high fat diet (HFD). The body and liver weight, blood glucose, serum transaminases and lipid levels and markers of hepatic inflammation were measured...
April 12, 2018: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/29656466/evaluation-of-high-fat-high-fructose-diet-treatment-in-factor-viii-coagulation-factor-deficient-mouse-model
#15
Alaknanda Mishra, Shailendra Arindkar, Preeti Sahay, Jerald Mahesh Kumar, Pramod K Upadhyay, Subeer S Majumdar, Perumal Nagarajan
Non-alcoholic fatty liver disease (NAFLD)-like conditions enhance the production and action of clotting factors in humans. However, studies examining the effect of NAFLD due to high-fat high-fructose (HFHF) diet in factor VIII-deficient (haemophilia A) animals or patients have not been reported previously. In this study, we investigated the individual role of factor VIII in the progression of diet-induced NAFLD in the factor 8-/- (F8-/- ) mouse model system and its consequences on the haemophilic status of the mice...
April 15, 2018: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/29656250/exposure-to-environmental-level-phenanthrene-induces-a-nash-like-phenotype-in-new-born-rat
#16
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/29656210/micheliolide-alleviates-hepatic-steatosis-in-db-db-mice-by-inhibiting-inflammation-and-promoting-autophagy-via-ppar-%C3%AE-mediated-nf-%C3%B0%C2%BAb-and-ampk-mtor-signaling
#17
Juan Zhong, Wangqiu Gong, Jing Chen, Yao Qing, Shuyue Wu, Hongbei Li, Chunxi Huang, Yihua Chen, Yuxian Wang, Zhaozhong Xu, Wenting Liu, HongYu Li, Haibo Long
The anti-inflammatory, immunomodulatory, and anticancer effects of micheliolide (MCL) isolated from Michelia champaca were previously reported, but its role and underlying mechanisms in relieving liver steatosis remain unclear. Herein, we investigated the effects of MCL on hepatic steatosis using a db/db mouse model and lipid mixture (LM)-induced AML12 and LO2 cells. The body and liver weights, food consumption, lipid content and liver aminotransferase levels in serum, the lipid content and inflammatory cytokine levels in liver tissue, and the extent of hepatic steatosis in db/db mice were increased compared with those in db/m mice, and these increases were reversed by MCL treatment...
April 12, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29656110/targeting-hepatic-pyruvate-dehydrogenase-kinases-restores-insulin-signaling-and-mitigates-chrebp-mediated-lipogenesis-in-diet-induced-obese-mice
#18
Cheng-Yang Wu, Shih-Chia Tso, Jacinta L Chuang, Wen-Jun Gui, Mingliang Lou, Gaurav Sharma, Chalermchai Khemtong, Xiangbing Qi, R Max Wynn, David T Chuang
OBJECTIVE: Mitochondrial pyruvate dehydrogenase kinases 1-4 (PDKs1-4) negatively regulate activity of the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation. PDKs play a pivotal role in maintaining energy homeostasis and contribute to metabolic flexibility by attenuating PDC activity in various mammalian tissues. Cumulative evidence has shown that the up-regulation of PDK4 expression is tightly associated with obesity and diabetes. In this investigation, we test the central hypothesis that PDKs1-4 are a pharmacological target for lowering glucose levels and restoring insulin sensitivity in obesity and type 2 diabetes (T2D)...
March 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29656108/epoxygenase-inactivation-exacerbates-diet-and-aging-associated-metabolic-dysfunction-resulting-from-impaired-adipogenesis
#19
Antoni Olona, Ximena Terra, Jeong-Hun Ko, Carme Grau-Bové, Montserrat Pinent, Anna Ardevol, Ana Garcia Diaz, Aida Moreno-Moral, Matthew Edin, David Bishop-Bailey, Darryl C Zeldin, Timothy J Aitman, Enrico Petretto, Mayte Blay, Jacques Behmoaras
OBJECTIVE: When molecular drivers of healthy adipogenesis are perturbed, this can cause hepatic steatosis. The role of arachidonic acid (AA) and its downstream enzymatic cascades, such as cyclooxygenase, in adipogenesis is well established. The exact contribution of the P450 epoxygenase pathway, however, remains to be established. Enzymes belonging to this pathway are mainly encoded by the CYP2J locus which shows extensive allelic expansion in mice. Here we aimed to establish the role of endogenous epoxygenase during adipogenesis under homeostatic and metabolic stress conditions...
March 9, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29655841/lysosomal-acid-lipase-deficiency-allograft-recurrence-and-liver-failure-clinical-outcomes-of-18-liver-transplantation-patients
#20
REVIEW
Donna Lee Bernstein, Steven Lobritto, Alina Iuga, Helen Remotti, Thomas Schiano, Maria Isabel Fiel, Manisha Balwani
Lysosomal acid lipase deficiency (LAL-D) results in progressive microvesicular hepatosteatosis, fibrosis, cirrhosis, dyslipidemia, and vascular disease. Interventions available prior to enzyme replacement therapy development, including lipid lowering medications, splenectomy, hematopoietic stem cell and liver transplantation were unsuccessful at preventing multi-systemic disease progression, and were associated with significant morbidity and mortality. We report two sisters, diagnosed in infancy, who succumbed to LAL-D with accelerated disease progression following splenectomy and liver transplantation...
March 27, 2018: Molecular Genetics and Metabolism
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