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Non-alcoholic steatosis

Milla-Maria Tauriainen, Ville Männistö, Dorota Kaminska, Maija Vaittinen, Vesa Kärjä, Pirjo Käkelä, Sari Venesmaa, Helena Gylling, Jussi Pihlajamäki
Background & aims : Non-alcoholic fatty liver disease (NAFLD) associates with low levels of serum plant sterols in cross-sectional studies. However, parenterally given plant sterols may lead to liver injury. In addition, it has been suggested that the hepatic sterol transport mechanisms are altered in NAFLD. Therefore, we investigated the association between serum, liver and bile plant sterols and sitostanol with NAFLD. Methods : Out of the 138 individuals (age: 46.3±8.9, BMI: 43.3±6.9 kg/m², 28% men and 72% women), 44 could be histologically categorized to have normal liver, and 94 to have NAFLD...
March 14, 2018: Bioscience Reports
Prahlad K Rao, Kate Merath, Eugene Drigalenko, Avinash Y L Jadhav, Richard A Komorowski, Matthew I Goldblatt, Anand Rohatgi, Mark A Sarzynski, Samer Gawrieh, Michael Olivier
Background: Metabolic diseases such as obesity and diabetes are associated with changes in high-density lipoprotein (HDL) particles, including changes in particle size and protein composition, often resulting in abnormal function. Recent studies suggested that patients with non-alcoholic fatty liver disease (NAFLD), including individuals with non-alcoholic steatohepatitis (NASH), have smaller HDL particles when compared to individuals without liver pathologies. However, no studies have investigated potential changes in HDL particle protein composition in patients with NAFLD, in addition to changes related to obesity, to explore putative functional changes of HDL which may increase the risk of cardiovascular complications...
2018: Clinical Proteomics
Dandan Huang, Baoqing Liu, Kai Huang, Kun Huang
Metabolic disorders, including obesity, non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and diabetes, are complex and progressive diseases. Enoyl coenzyme A hydratase 1 (Ech1) is an enzyme that participates in mitochondrial fatty acid β-oxidation; however, little is known regarding the significance of Ech1 in the pathogenesis of metabolic disorders. Here, we report that high-fat-diet (HFD)-induced and genetic obesity could increase Ech1 expression in mouse liver. The overexpression of Ech1 using adeno-associated virus (AAV2/8) ameliorated HFD-induced liver lipid accumulation and accompanying liver injury...
March 8, 2018: Biochemical and Biophysical Research Communications
Shanshan Shao, Zhenyu Yao, Jiayu Lu, Yongfeng Song, Zhao He, Chunxiao Yu, Xiaoming Zhou, Lifang Zhao, Jiajun Zhao, Ling Gao
Increasing prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide has necessitated a more thorough understanding of it and expanded the scope of research in this field. Women are more resistant to NAFLD than men despite equal exposure to major risk factors, such as obesity or hyperlipidemia. Female resistance is hormone-dependent, as evidenced by the sharp increase in NAFLD incidence in post-menopausal women who do not take hormone replacement therapy. Here, we found that the estrogen-responsive pituitary hormone prolactin (PRL), through specific PRL receptor (PRLR), down-regulates hepatic triglyceride (TG) accumulation...
March 7, 2018: Biochemical and Biophysical Research Communications
Karen Louise Thomsen, Francesco De Chiara, Krista Rombouts, Hendrik Vilstrup, Fausto Andreola, Rajeshwar P Mookerjee, Rajiv Jalan
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases ranging from steatosis, through non-alcoholic steatohepatitis (NASH) to cirrhosis. The development of fibrosis is the most important factor contributing to NASH-associated morbidity and mortality. Hepatic stellate cells (HSCs) are responsible for extracellular matrix deposition in conditions of frank hepatocellular injury and are key cells involved in the development of fibrosis. In experimental models and patients with NASH, urea cycle enzyme gene and protein expression is reduced resulting in functional reduction in the in vivo capacity for ureagenesis and subsequent hyperammonemia at a pre-cirrhotic stage...
April 2018: Medical Hypotheses
Stephen A Harrison, Mary E Rinella, Manal F Abdelmalek, James F Trotter, Angelo H Paredes, Hays L Arnold, Marcelo Kugelmas, Mustafa R Bashir, Mark J Jaros, Lei Ling, Stephen J Rossi, Alex M DePaoli, Rohit Loomba
BACKGROUND: Non-alcoholic steatohepatitis is a chronic liver disease characterised by the presence of hepatic steatosis, inflammation, and hepatocellular injury, for which no Food and Drug Administration (FDA)-approved treatment exists. FGF19 is a hormone that regulates bile acid synthesis and glucose homoeostasis. We aimed to assess the safety and efficacy of NGM282, an engineered FGF19 analogue, for the treatment of non-alcoholic steatohepatitis. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 study, we recruited patients aged 18-75 years with biopsy-confirmed non-alcoholic steatohepatitis as defined by the non-alcoholic steatohepatitis clinical research network histological scoring system, from hospitals and gastroenterology and liver clinics in Australia and the USA...
March 5, 2018: Lancet
Myong-Min Lee, Hyeong-Geug Kim, Sung-Bae Lee, Jin-Seok Lee, Won-Yong Kim, Seung-Hoon Choi, Sam-Keun Lee, Chang-Kyu Byun, Pung-Mi Hyun, Chang-Gue Son
BACKGROUND: The prevalence of Non-alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) has increased by 15-39% worldwide, but no pharmaceutical therapeutics exists. HYPOTHESIS/PURPOSE: This study investigated anti-hepatosteatotic effect of CGplus (a standardized herbal composition of Artemisia iwayomogi, Amomum xanthioides, and Salvia miltiorrhiza) and its underlying mechanisms in a tunicamycin-induced NASH model. METHODS: C57/BL6J male mice were orally administrated CGplus (50, 100, or 200 mg/kg), dimethyl dimethoxy biphenyl dicarboxylate (DDB, 50 mg/kg) or distilled water daily for 5 days...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Shinji Takai, Denan Jin
Non-alcoholic steatohepatitis (NASH) is characterized by inflammation and fibrosis, in addition to steatosis, of the liver, but no therapeutic agents have yet been established. The mast cell protease chymase can generate angiotensin II, matrix metalloproteinase-9 and transforming growth factor-β, all of which are associated with liver inflammation or fibrosis. In animal models of NASH, augmented chymase has been observed in the liver. In histological analysis, chymase inhibitor prevented hepatic steatosis, inflammation, and fibrosis...
2018: Frontiers in Pharmacology
Lotte Kors, Elena Rampanelli, Geurt Stokman, Loes Butter, Ntsiki M Held, Nike Claessen, Per W B Larsen, Joanne Verheij, Coert J Zuurbier, Gerhard Liebisch, Gerd Schmitz, Stephen E Girardin, Sandrine Florquin, Riekelt H Houtkooper, Jaklien C Leemans
NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that is uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we report that NLRX1 is essential in regulating cellular metabolism in non-immune parenchymal hepatocytes by decreasing mitochondrial fatty acid-dependent oxidative phosphorylation (OXPHOS) and promoting glycolysis. NLRX1 loss in mice has a profound impact on the prevention of diet-induced metabolic syndrome parameters, non-alcoholic fatty liver disease (NAFLD) progression, and renal dysfunction...
March 4, 2018: Biochimica et Biophysica Acta
Yung-Tsung Chen, Yu-Chun Lin, Jin-Seng Lin, Ning-Sun Yang, Ming-Ju Chen
SCOPE: Non-alcoholic fatty liver disease (NAFLD) is a common disease that is concomitant with obesity, resulting in increased mortality. To date, the efficiency of NAFLD treatment still needs to be improved. Therefore, we aimed to evaluate the effect of Lactobacillus mali APS1, which was isolated from sugary kefir, on hepatic steatosis in rats fed a high-fat diet (HFD). METHODS AND RESULTS: Sprague Dawley rats were fed a control diet, a high-fat diet with saline and a high-fat diet with APS1 intervention by gavage daily for 12 weeks...
March 5, 2018: Molecular Nutrition & Food Research
Hui Liang, Yutong Wang
Abnormal lipid metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH). The ATP-binding cassette transporter A1 (ABCA1) protein mediates the transport of cholesterol and phospholipids from cells to apolipoprotein A-I (apoA-I) to generate nascent HDL particles. Previous studies revealed that the overexpression of ABCA1 alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effect of berberine (BBR) on ABCA1 in QSG-7701 hepatocytes and in mice. BBR decreased hepatic cholesterol and triglyceride levels...
March 2, 2018: Biochemical and Biophysical Research Communications
Gilles Fouret, Sylvie Gaillet, Jerome Lecomte, Beatrice Bonafos, Ferdinand Djohan, Bruno Barea, Eric Badia, Charles Coudray, Christine Feillet-Coudray
The incidence of obesity and its metabolic complications are rapidly increasing and become a major public health issue. This trend is associated with an increase in the prevalence of non-alcoholic fatty liver disease (NAFLD), insulin resistance and diabetes. The sequence of events leading to NAFLD progression and mitochondrial dysfunction and their interrelation remains to be elucidated. This study aimed to explore the installation and progression of NAFLD and its association with the liver mitochondrial structure and activity changes in rats fed an obesogenic diet up to 20 weeks...
February 2018: British Journal of Nutrition
Daniel F Vatner, Leigh Goedeke, Joao-Paulo G Camporez, Kun Lyu, Ali R Nasiri, Dongyan Zhang, Sanjay Bhanot, Susan F Murray, Christopher D Still, Glenn S Gerhard, Gerald I Shulman, Varman T Samuel
AIMS/HYPOTHESIS: Targeting regulators of adipose tissue lipoprotein lipase could enhance adipose lipid clearance, prevent ectopic lipid accumulation and consequently ameliorate insulin resistance and type 2 diabetes. Angiopoietin-like 8 (ANGPTL8) is an insulin-regulated lipoprotein lipase inhibitor strongly expressed in murine adipose tissue. However, Angptl8 knockout mice do not have improved insulin resistance. We hypothesised that pharmacological inhibition, using a second-generation antisense oligonucleotide (ASO) against Angptl8 in adult high-fat-fed rodents, would prevent ectopic lipid accumulation and insulin resistance by promoting adipose lipid uptake...
March 1, 2018: Diabetologia
Patricia Rosales-Cruz, Mayra Domínguez-Pérez, Elizabeth Reyes-Zárate, Oscar Bello-Monroy, Cristina Enríquez-Cortina, Roxana Miranda-Labra, Leticia Bucio, Luis Enrique Gómez-Quiroz, Emilio Rojas-Del Castillo, María Concepción Gutiérrez-Ruíz, Verónica Souza-Arroyo
Metabolic factors are the major risk of non-alcoholic fatty liver disease, although other factors may contribute steatosis. Cadmium exposure produces histopathological and molecular changes in liver, which are consistent with steatosis. In the present study, we describe the effect of low cadmium acute treatment on hepatocytes obtained from mice fed with a high cholesterol diet. Our data suggest that hepatocytes with cholesterol overload promote an adaptive response against cadmium-induced acute toxicity by up-regulating anti-apoptotic proteins, managing ROS overproduction, increasing GSH synthesis and MT-II content to avoid protein oxidation...
February 24, 2018: Toxicology
Giuseppina R Umano, Sonia Caprio, Anna Di Sessa, Naga Chalasani, Daniel J Dykas, Bridget Pierpont, Allen E Bale, Nicola Santoro
OBJECTIVES: Non alcoholic fatty liver disease (NAFLD) is a leading cause of liver damage in childhood, its occurrence is influenced by genetic and environmental factors. Recently, the rs626283 polymorphism in the MBOAT7 gene has been found to be associated with alcoholic liver disease and NAFLD in adults. METHODS: In a multiethnic cohort of obese children and adolescents we genotyped the rs626283 polymorphism in the MBOAT7 gene, evaluated insulin sensitivity by an oral glucose tolerance test, and measured the intra-hepatic fat content (HFF%) by magnetic resonance imaging...
February 27, 2018: American Journal of Gastroenterology
Marcin Krawczyk, Heike Bantel, Monika Rau, Jörn M Schattenberg, Frank Grünhage, Anita Pathil, Münevver Demir, Johannes Kluwe, Tobias Boettler, Susanne N Weber, Andreas Geier, Frank Lammert
Non-alcoholic fatty liver disease (NAFLD) is frequent among obese individuals with metabolic syndrome. Variants PNPLA3 p.I148M, TM6SF2 p.E167K and MBOAT7 rs641738 are associated with higher liver fat contents. Here we analyzed 63 biopsied non-obese, non-diabetic patients with NAFLD (39 men, age: 20-72 years) recruited within the German NAFLD CSG program. The frequencies of the PNPLA3, TM6SF2 and MBOAT7 polymorphisms were compared with the remaining patients in the NAFLD CSG cohort and with a control population (n = 174)...
February 26, 2018: Journal of Human Genetics
Yasuyo Urasaki, Chi Zhang, Ji-Xin Cheng, Thuc T Le
Current assessment of non-alcoholic fatty liver disease (NAFLD) with histology is time-consuming, insensitive to early-stage detection, qualitative, and lacks information on etiology. This study explored alternative methods for fast and quantitative assessment of NAFLD with hyperspectral stimulated Raman scattering (SRS) microscopy and nanofluidic proteomics. Hyperspectral SRS microscopy quantitatively measured liver composition of protein, DNA, and lipid without labeling and sensitively detected early-stage steatosis in a few minutes...
February 26, 2018: Scientific Reports
Islam N Mohamed, Nahla Reda Sarhan, Mohamed Ahmed Eladl, Azza B El-Remessy, Mohamed El-Sherbiny
Endemic prevalence of obesity is associated with alarming increases in non-alcoholic steatohepatitis (NASH) with limited available therapeutics. Toll-like receptor2 (TLR2) and Nod-like receptor protein 3 (NLRP3) Inflammasome are implicated in hepatic steatosis, inflammation and fibrosis; the histological landmark stages of NASH. TXNIP, a member of α-arrestin family activates NLRP3 in response to various danger stimuli. The aim of current work was to investigate the effect of TXNIP genetic deletion on histological manifestations of high fat diet-induced steatohepatitis and activation of TLR2-NLRP3-inflammasome axis...
February 23, 2018: Acta Histochemica
Hirofumi Fukushima, Shunhei Yamashina, Atsushi Arakawa, Gentaro Taniguchi, Tomonori Aoyama, Akira Uchiyama, Kazuyoshi Kon, Kenichi Ikejima, Sumio Watanabe
BACKGROUND: Hepatic inclusion composed of autophagy-specific substrate p62 is one of the histological features of non-alcoholic fatty liver disease (NAFLD) and can be a precursor to hepatic carcinogenesis. The expression of p62 was enhanced by not only autophagic dysfunction but also oxidative stress and inflammation. M1/M2 phenotypic balance of macrophages plays a pivotal role in the progression of NAFLD. We evaluated the correlation between macrophage-polarization and the formation of p62 aggregation in NAFLD...
February 26, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Chi Han Li, Shing Chun Tang, Chi Hin Wong, Yan Wang, Jian-Dong Jiang, Yangchao Chen
Berberine is a Chinese herbal medicine extracted from rhizoma coptidis that functions to improve insulin resistance, hyperlipidemia, hepatosteatosis and inflammation. Berberine can modify the activity of cell metabolism and signaling pathways by regulating expression of genes. However, the roles and effects of differential microRNA (miRNA) expression induced by berberine treatment are largely unexplored. It is believed that miRNAs expression modified by berberine contributes to its therapeutic effects to diseases such as hepatosteatosis and non-alcoholic fatty liver disease...
February 22, 2018: European Journal of Pharmacology
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