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Francisco Heine Ferreira Machado, Heladio Feitosa de Castro Filho, Rodrigo Feitosa de Albuquerque Lima Babadopulos, Hermano Alexandre Lima Rocha, José Lima de Carvalho Rocha, Manoel Odorico de Moraes Filho
PURPOSE: To evaluate the contribution of ursodeoxycholic acid (UDCA) in the first 12 months after Roux-en-Y gastric bypass in the prevention of gallstone formation. METHODS: A community-based clinical trial was conducted. A total of 137 patients were included in the study; 69 were treated with UDCA, starting 30 days after the surgery, at a dose of 150 mg twice daily (300 mg/day) over a period of 5 consecutive months (GROUP A), and 68 were control patients (GROUP B)...
February 14, 2019: Acta Cirúrgica Brasileira
Carolina A Miranda, Tatiele E Schönholzer, Eduardo Klöppel, Yuri K Sinzato, Gustavo T Volpato, Débora C Damasceno, Kleber E Campos
Fructose consumption has increased worldwide, and it has been associated with the development of metabolic diseases such as insulin resistance (IR) and steatosis. The aim was to evaluate if lower fructose concentrations may cause pancreatic structural abnormalities, leading to a glucose intolerance without steatosis in male rats. Young male rats orally received 7% fructose solution for 12 weeks. Body weight, food, water, and energy intake were measured. An oral glucose tolerance test (OGTT) was performed. After final experimental period, all rats were anaesthetized and killed...
February 14, 2019: Anais da Academia Brasileira de Ciências
Leon A Adams
Non-alcoholic steatohepatitis (NASH) is an increasingly common cause of cirrhosis, hepatocellular carcinoma, and liver-related death (LRD). Consequently, there is a critical need for effective drug therapy that improves clinically relevant end-points. Hepatic steatosis assessed by magnetic resonance imaging-proton density fat fraction is increasingly used in the early phase trials examining drugs with anti-steatotic effects. However, the prognostic significance of a reduction in steatosis is unknown, and thus, phase 3 trials require a histological end-point of NASH resolution without fibrosis progression...
February 19, 2019: Hepatology International
Geum-Hwa Lee, Hwa-Young Lee, Sun-Ah Park, Tai-Sun Shin, Han-Jung Chae
The recent discovery that the impairment of autophagic flux in non-alcoholic fatty liver disease (NAFLD) might be a strong determining factor in steatosis suggests the potential of therapeutic control of autophagic flux with natural agents in restoring NAFLD. We investigated the potential of Eucommia ulmoides leaf extract (EUL) to control dyslipidemia in NAFLD. EUL supplementation (200 mg/kg) promoted recovery from high fat diet (HFD)-induced lipid dysmetabolism. This hepatoprotective efficacy was accompanied by suppression of endoplasmic reticulum (ER) stress, enhancing lysosomal functions, and thereby increasing autophagic flux...
February 18, 2019: Nutrients
Gabriela Handzlik, Michał Holecki, Joanna Kozaczka, Michał Kukla, Katarzyna Wyskida, Leszek Kędzierski, Krzysztof Pawlicki, Jan Duława
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is among the most common causes of liver disease worldwide. There is growing evidence on pathogenesis and pathophysiology of NAFLD. However, there is still no universally accepted pharmacotherapy protocol. METHODS: The study was conducted on 42 patients with NAFLD. They were randomized to dietary treatment alone (n = 21) or to diet and metformin therapy (n = 21). Liver ultrasonography, controlled attenuation parameter (CAP), liver stiffness (LS), complete blood count, anthropometric and biochemical parameters were obtained before treatment (baseline), and after 3 and 5 months of the therapy...
October 26, 2018: Pharmacological Reports: PR
Yueyue Lei, Leilei Gong, Fanggen Tan, Yixiao Liu, Shuangshuang Li, Houwang Shen, Min Zhu, Weiwei Cai, Fei Xu, Bao Hou, Yuetao Zhou, Hongxiu Han, Liying Qiu, Haijian Sun
Destructive glucose and lipid metabolism in the liver is a crucial characteristic of type 2 diabetes mellitus (T2DM), eventually leading to insulin resistance and subsequent hyperglycemia and hyperlipidemia. Vaccarin is an active flavonoid glycoside associated with various biological functions, but its effects on glucose and lipid metabolic disorder in T2DM are still unclear. In this study, glucosamine (GlcN) and free fatty acids (FFAs, oleate/palmitate, 2:1 ratio) were applied to mimic insulin resistance and lipid deposition in HepG2 cells, respectively...
February 16, 2019: European Journal of Pharmacology
Hirotsugu Nakai, Shigeki Arizono, Hiroyoshi Isoda, Kaori Togashi
OBJECTIVE: The purpose of this study was to evaluate the imaging characteristics of liver metastases overlooked at contrast-enhanced CT. MATERIALS AND METHODS: The records of 746 patients with a diagnosis of liver metastases from colorectal, breast, gastric, or lung cancer between November 2010 and September 2017 were reviewed. Images were reviewed when liver metastases were first diagnosed, and images from prior contrast-enhanced CT examinations were checked if available...
February 19, 2019: AJR. American Journal of Roentgenology
Wajahat Z Mehal, Rohit Loomba
With chronic overnutrition the storage of triglyceride in numerous cells including hepatocytes seems inevitable, and can be explained by well recognized pathways of lipid metabolism. This seemingly obvious association between chronic overnutrition and hepatocyte steatosis appears to be regulated by an unnervingly complex set of pathways that are not traditionally thought of as metabolic regulators. The study of regulation of steatosis is traditionally approached by hypothesis driven manner which examine the role of an individual molecules and pathways...
February 19, 2019: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Isabel Schulien, Birgit Hockenjos, Annette Schmitt-Graeff, Markus Große Perdekamp, Marie Follo, Robert Thimme, Peter Hasselblatt
Progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to non-alcoholic steatohepatitis (NASH) is a key step of NASH pathogenesis. The AP-1 transcription factor c-Jun is an important regulator of hepatic stress responses, but its contribution to NASH pathogenesis remains poorly defined. We therefore addressed c-Jun expression in liver biopsies of patients with steatosis and NASH. The role of c-Jun during NASH pathogenesis was analyzed mechanistically in c-Jun mutant mice fed with a methionine- and choline-deficient diet (MCDD)...
February 18, 2019: Cell Death and Differentiation
Menno Hoekstra, Joya E Nahon, Laura M de Jong, Mara J Kröner, Lidewij R de Leeuw, Miranda Van Eck
The nuclear receptor liver X receptor (LXR) impacts on cholesterol metabolism as well as hepatic lipogenesis via transcriptional regulation. It is proposed that inhibition of the protein arginine methyltransferase 3 (PRMT3) uncouples these two transcriptional pathways in vivo by acting as a specific lipogenic coactivator of LXR. Here we validated the hypothesis that treatment with the allosteric PRMT3 inhibitor SGC707 will diminish the hepatic steatosis extent, while leaving global cholesterol metabolism, important in cholesterol-driven pathologies like atherosclerosis, untouched...
February 15, 2019: Biochimica et biophysica acta. Molecular basis of disease
Shu-Fang Xia, Yu-Yu Qiu, Li-Mei Chen, Yu-Yu Jiang, Wei Huang, Zhen-Xing Xie, Xue Tang, Jin Sun
Hepatic microRNAs (miRs) regulate local thyroid hormone (TH) action and TH-related lipid metabolism. We previously found that myricetin effectively ameliorated hepatic steatosis by targeting PPAR signaling pathway, in which the differentially expressed genes were TH-responsive. The present study was designed to explore the mechanism by which myricetin regulated miR-dependent TH action and lipid metabolism on high-fat diet (HFD)-induced hepatic steatosis. C57BL/6J mice were fed a HFD with or without 100 mg kg-1 myricetin by oral gavage for 16 weeks (n = 8 for each group)...
February 18, 2019: Food & Function
Rehab M Badi, Dalia G Mostafa, Eman F Khaleel, Huda H Satti
Non-alcoholic fatty liver disease (NAFLD) is associated with hepatic insulin resistance (IR). Resveratrol (RES) a potent hypolipidemic dietary polyphenol has been identified for its ability to prevent hepatic steatosis and hepatic IR in high-fat diet (HFD)-fed murine models of NAFLD. In the present study, we have carried an in vivo animal experiment to identify a novel mechanism for RES protective action. Sub-chronic (45 days) RES pre-treatment in 3 days HFD-fed adult Wistar rats prevented early hepatic IR through inhibiting PKC/JNK activation; decreasing p-IRS (Ser307 ) and increasing p-IRS(Tyr612 ), p-Akt(Ser473 ) and p-GSK3(Ser9 )...
February 17, 2019: Clinical and Experimental Pharmacology & Physiology
Oren Rom, Guan Xu, Yanhong Guo, Yunhao Zhu, Huilun Wang, Jifeng Zhang, Yanbo Fan, Wenying Liang, Haocheng Lu, Yuhao Liu, Michael Aviram, Zhipeng Liu, Seongho Kim, Wanqing Liu, Xueding Wang, Y Eugene Chen, Luis Villacorta
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are reaching global epidemic proportions. Lack of non-invasive diagnostic tools and effective therapies constitute two of the major hurdles for a bona fide treatment and a reversal of NASH progression and/or regression of the disease. Nitro-oleic acid (OA-NO2 ) has been proven effective in multiple experimental models of inflammation and fibrosis. Thus, the potential benefit of in vivo administration of OA-NO2 to treat advanced NAFLD was tested herein in a model of long-term NASH diet-induced liver damage...
February 13, 2019: EBioMedicine
Daniel Lindén, Andrea Ahnmark, Piero Pingitore, Ester Ciociola, Ingela Ahlstedt, Anne-Christine Andréasson, Kavitha Sasidharan, Katja Madeyski-Bengtson, Magdalena Zurek, Rosellina M Mancina, Anna Lindblom, Mikael Bjursell, Gerhard Böttcher, Marcus Ståhlman, Mohammad Bohlooly-Y, William G Haynes, Björn Carlsson, Mark Graham, Richard Lee, Sue Murray, Luca Valenti, Sanjay Bhanot, Peter Åkerblad, Stefano Romeo
OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of advanced chronic liver disease. The progression of NAFLD, including nonalcoholic steatohepatitis (NASH), has a strong genetic component, and the most robust contributor is the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 encoding the 148M protein sequence variant. We hypothesized that suppressing the expression of the PNPLA3 148M mutant protein would exert a beneficial effect on the entire spectrum of NAFLD...
February 5, 2019: Molecular Metabolism
Peter Lykke Eriksen, Michael Sørensen, Henning Grønbæk, Stephen Hamilton-Dutoit, Hendrik Vilstrup, Karen Louise Thomsen
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major health concern affecting 25% of the world's population. It is generally held that a fatty liver does not influence liver function, but quantitative measurements of metabolic liver functions have not been systematically performed. We aimed to study selected hepatocellular metabolic functions in patients with different stages of NAFLD. METHODS: Twenty-five non-diabetic, biopsy-proven NAFLD patients [12 with simple steatosis; 13 with non-alcoholic steatohepatitis (NASH)] and ten healthy controls were included in a cross-sectional study...
February 12, 2019: Clinics and Research in Hepatology and Gastroenterology
Nicholas K H Khoo, Marco Fazzari, Dionysios V Chartoumpekis, Lihua Li, Danielle Aparecida Guimaraes, Gavin E Arteel, Sruti Shiva, Bruce A Freeman
Non-alcoholic fatty liver disease (NAFLD) is linked to obesity and insulin resistance and is the most prevalent chronic liver disease. During the development of obesity and NAFLD, mitochondria adapt to the increased lipid load in hepatocytes by increasing the rate of fatty acid oxidation. In concert with this, reactive species (RS) generation is increased, damaging hepatocytes and inducing inflammation. Hepatic mitochondrial dysfunction is central to the pathogenesis of NAFLD via undefined mechanisms. There are no FDA approved treatments for NAFLD other than weight loss and management of glucose tolerance...
February 1, 2019: Redox Biology
David Houghton, Paweł Zalewski, Kate Hallsworth, Sophie Cassidy, Christian Thoma, Leah Avery, Joanna Slomko, Timothy Hardy, Alastair D Burt, Dina Tiniakos, Kieren G Hollingsworth, Roy Taylor, Christopher P Day, Steven Masson, Stuart McPherson, Quentin M Anstee, Julia L Newton, Michael I Trenell
BACKGROUND: Cardiovascular disease is the principle cause of death in patients with elevated liver fat unrelated to alcohol consumption, more so than liver related morbidity and mortality. OBJECTIVES: The aim of this study was to evaluate the relationship between liver fat and cardiac and autonomic function. Secondly, how impairment in cardiac and autonomic function is influenced by metabolic risk factors. METHODS: Cardiovascular and autonomic function were assessed in 96 sedentary individuals: 1) NAFLD (n = 46, hepatic steatosis >5% by magnetic resonance spectroscopy), 2) Hepatic steatosis and alcohol (DAFLD) (n = 16, >5%, consuming >20g/day of alcohol) and 3) CONTROLS (n = 34, no cardiac, liver or metabolic disorders, <20g/day of alcohol)...
February 12, 2019: Journal of Hepatology
Domenico Serino, Chiara Davico, Nicola Specchio, Carlo Efisio Marras, Franco Fioretto
Berardinelli-Seip syndrome, or congenital generalized lipodystrophy type 2 (CGL2), is characterized by a lack of subcutaneous adipose tissue and precocious metabolic syndrome with insulin resistance, resulting in diabetes, dyslipidaemia, hepatic steatosis, cardiomyopathy, and acanthosis nigricans. Most reported mutations are associated with mild, non-progressive neurological impairment. We describe the clinical and EEG data of a patient with progressive myoclonus epilepsy (PME), CGL2, and progressive neurological impairment, carrying a homozygous BSCL2 nonsense mutation...
February 15, 2019: Epileptic Disorders: International Epilepsy Journal with Videotape
Zahra Darabi, Mina Darand, Zahra Yari, Mehdi Hedayati, Amirhosein Faghihi, Shahram Agah, Azita Hekmatdoost
OBJECTIVES: The aim of this study was to investigate the effects of citrulline (Cit) supplementation on inflammatory markers and liver histopathology in patients with non-alcoholic fatty liver disease (NAFLD). In this clinical trial, fifty NAFLD patients were assigned to receive 2 g/day Cit or placebo for 3 months. RESULTS: At the end of study, serum high sensitive C-reactive protein (hs-CRP) and activity of nuclear factor kappa B (NF-κB) were reduced in Cit group significantly more than placebo group (P-value = 0...
February 15, 2019: BMC Research Notes
Ye Bi, Ji-Lan Wang, Ming-Long Li, Jie Zhou, Xiang-Lan Sun
OBJECTIVES: Pancreas steatosis is the description of fat accumulation in the pancreatic gland. The prevalence and development mechanisms of pancreatic steatosis in patients with metabolic disorders still remain unclear. The aim of this study is to systematically review the association between pancreatic steatosis and metabolic co-morbidities. METHODS: We performed a systematic search strategy using three electronic databases (MEDLINE, Scopus, and Embase) for relevant studies concerning the associations of pancreatic steatosis with metabolic syndrome (MetS) and its clinical relevance from inception until September 30, 2018...
February 14, 2019: Diabetes/metabolism Research and Reviews
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