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Non-alcoholic fat liver

Maggie A Stanislawski, Catherine A Lozupone, Brandie D Wagner, Merete Eggesbø, Marci K Sontag, Nichole Nusbacher, Mercedes Martinez, Dana Dabelea
BACKGROUND: Recent evidence supports that the gut microbiota may be involved in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), and may also offer avenues for treatment or prevention. METHODS: We investigated the associations among gut microbiota, diet and hepatic fat fraction (HFF) in 107 adolescents. Magnetic Resonance Imaging (MRI) was used to assess HFF, and 16S rRNA gene sequencing was performed on collected fecal samples. Dietary intake was assessed using Food Frequency Questionnaires...
March 14, 2018: Pediatric Research
Yi-Yuan Zheng, Miao Wang, Xiang-Bing Shu, Pei-Yong Zheng, Guang Ji
AIM: To elucidate the potential role of autophagy and the protective effects of Jiang Zhi Granule (JZG) in metabolic stress-induced hepatocyte injury. METHODS: An in vitro and in vivo approach was used in this study. HepG2 cells were incubated in culture medium containing palmitate (PA; 0, 0.1, 0.2, 0.3, 0.4 or 0.5 mmol/L) and treated with or without JZG (100 μg/mL) for 24 h or 48 h, and the progression of autophagy was visualized by stable fluorescence-expressing cell lines LC3 and p62...
March 7, 2018: World Journal of Gastroenterology: WJG
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
Claus Uhrenholt Christensen, Emilie Glavind, Karen Louise Thomsen, Yong Ook Kim, Sara Heebøll, Detlef Schuppan, Stephen Hamilton-Dutoit, Christian Würtz Heegaard, Henning Grønbæk
BACKGROUND AND AIMS: Hepatic cholesterol deposition drives inflammation and fibrosis in non-alcoholic steatohepatitis (NASH). The Niemann-Pick type C2 (NPC2) protein plays an important role in regulating intracellular cholesterol trafficking and homeostasis. We hypothesized that intravenous NPC2 supplementation reduces cholesterol accumulation, hepatic inflammation and fibrogenesis in a nutritional NASH rat model. METHODS: Rats were fed a high-fat, high-cholesterol (HFHC) diet for four weeks resulting in moderately severe NASH...
2018: PloS One
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
Shoji Yamada, Yoko Takashina, Mitsuhiro Watanabe, Ryogo Nagamine, Yoshimasa Saito, Nobuhiko Kamada, Hidetsugu Saito
Gut microbiota plays a significant role in the development of hepatocellular carcinoma (HCC) in non-alcoholic steatohepatitis (NASH). However, understanding of the precise mechanism of this process remains incomplete. A new class steatohepatitis-inducing high-fat diet (HFD), namely STHD-01, can promote the development of HCC without the administration of chemical carcinogens. Using this diet, we comprehensively analyzed changes in the gut microbiota and its metabolic functions during the development of HCC in NASH...
February 9, 2018: Oncotarget
Andrew R Crawford, Naji Alamuddin, Anastassia Amaro
PURPOSE OF REVIEW: We review recent studies discussing the impact of pharmacologic agents for weight loss on clinical cardiovascular events, as well as cardiometabolic risk factors. RECENT FINDINGS: Pharmacotherapy with current FDA-approved medications for weight loss can significantly improve known risk factors for the development of cardiovascular disease such as hypertension, hyperlipidemia, insulin resistance, inflammatory biomarkers, and the quantity of visceral fat, as well as non-alcoholic fatty liver disease...
March 6, 2018: Current Atherosclerosis Reports
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
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
Christina Gallo-Ebert, Jamie Francisco, Hsing-Yin Liu, Riley Draper, Kinnari Modi, Michael D Hayward, Beverly K Jones, Olesia Buiakova, Virginia McDonough, Joseph T Nickels
MetS syndrome (MetS) is a term used to characterize individuals having at least three of the following diseases: obesity, dyslipidemia, hyperglycemia, insulin resistance, hypertension, and non-alcoholic fatty liver disease (NAFLD).  It is widespread and the number of individuals with MetS is increasing.  However, the events leading to the manifestation of MetS are not well understood.  Here, we show that loss of mARV1 in mice results in resistance to acquiring diseases associated with MetS.   Arv1-/- animals fed a high fat diet were resistant to diet-induced obesity, had lower blood cholesterol and triglycerides levels, and retained glucose tolerance and insulin sensitivity...
February 28, 2018: Journal of Biological Chemistry
Laura Palanker Musselman, Jill L Fink, Ezekiel J Maier, Jared A Gatto, Michael R Brent, Thomas J Baranski
Insulin resistance is associated with obesity, cardiovascular disease, non-alcoholic fatty liver disease, and type 2 diabetes. These complications are exacerbated by a high-calorie diet, which we used to model type 2 diabetes in Drosophila melanogaster Our studies focused on the fat body, an adipose- and liver-like tissue that stores fat and maintains circulating glucose. A gene regulatory network was constructed to predict potential regulators of insulin signaling in this tissue. Genomic characterization of fat bodies suggested a central role for the transcription factor Seven-up (Svp)...
February 27, 2018: Genetics
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
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
Lisa Rein-Fischboeck, Elisabeth M Haberl, Rebekka Pohl, Verena Schmid, Susanne Feder, Sabrina Krautbauer, Gerhard Liebisch, Christa Buechler
Adipose tissue dysfunction contributes to the pathogenesis of non-alcoholic steatohepatitis (NASH). The adapter protein alpha-syntrophin (SNTA) is expressed in adipocytes. Knock-down of SNTA increases preadipocyte proliferation and formation of small lipid droplets, which are both characteristics of healthy adipose tissue. To elucidate a potential protective role of SNTA in NASH, SNTA null mice were fed a methionine-choline-deficient (MCD) diet or an atherogenic diet which are widely used as preclinical NASH models...
February 20, 2018: Biochimica et Biophysica Acta
Tianxing Chen, Dong Yan, Xiaoying Cheng, XiaoJun Ji, Wu Yin
MicroRNAs are potential therapeutic targets for metabolic diseases. Here, miR-1224-5p was highly expressed in the livers of both high fat diet (HFD)-fed mice and obese (ob/ob) mice. To examine the potential role of miR-1224-5p, we constructed liver-specific adenoviral vectors expressing either an miR-1224-5p inhibitor sequence or miR-1224-5p mimic sequences. Following tail-vein vector injection, HFD-fed mice were examined for expression of lipogenic genes. We found that miR-1224-5p inhibitors significantly attenuated hepatic lipogenesis and steatosis in HFD-fed mice, while miR-1224-5p mimics promoted lipid accumulation in the liver of chow-fed C57BL/6 mice...
February 21, 2018: Endocrinology
I Barchetta, F A Cimini, R De Gioannis, G Ciccarelli, L Bertoccini, A Lenzi, M G Baroni, M G Cavallo
AIMS: Procollagen-III peptide (PIIINP) is a marker of fibrosis associated with increased cardio-metabolic risk and progression of chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH); its association with type 2 diabetes mellitus has not been elucidated yet. Aim of this study was to investigate the relationship between circulating PIIINP levels, metabolic traits and body fat distribution in subjects with T2DM with or without NAFLD. MATERIALS AND METHODS: Data from sixty-two T2DM subjects recruited in our Diabetes outpatient clinics at Sapienza University of Rome, Italy, were analysed...
February 22, 2018: Diabetes/metabolism Research and Reviews
Anne S Kramer, Bruce Latham, Luke A Diepeveen, Lingjun Mou, Geoffrey J Laurent, Caryn Elsegood, Laura Ochoa-Callejero, George C Yeoh
Hepatic progenitor cells (HPCs) play an important regenerative role in acute and chronic liver pathologies. Liver disease research often necessitates the grading of disease severity, and pathologists' reports are the current gold-standard for assessment. However, it is often impractical to recruit pathologists in large cohort studies. In this study we utilise PerkinElmer's "InForm" software package to semi-automate the scoring of patient liver biopsies, and compare outputs to a pathologist's assessment...
February 21, 2018: Scientific Reports
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