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Xilin Li, Zemin Wang, James E Klaunig
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the western countries. The histological spectrum of NAFLD includes simple steatosis, steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Nuclear receptors are a large group of ligand-dependent transcription factors that sense the environmental and endogenous changes and regulate numerous physiological and pathological processes. Accumulating evidence has suggested that a dysregulation of nuclear receptors in NAFLD may effect on the metabolism of endogenous and exogenous chemicals in the liver...
August 15, 2018: Toxicology
Eric M Desjardins, Gregory R Steinberg
PURPOSE OF REVIEW: The global prevalence of type 2 diabetes (T2D) is escalating at alarming rates, demanding the development of additional classes of therapeutics to further reduce the burden of disease. Recent studies have indicated that increasing the metabolic activity of brown and beige adipose tissue may represent a novel means to reduce circulating glucose and lipids in people with T2D. The AMP-activated protein kinase (AMPK) is a cellular energy sensor that has recently been demonstrated to be important in potentially regulating the metabolic activity of brown and beige adipose tissue...
August 17, 2018: Current Diabetes Reports
Su-Kyung Shin, Hyun-Woo Cho, Seung-Eun Song, Dae-Kyu Song
Obesity and insulin resistance are considered the main causes of nonalcoholic fatty liver disease (NAFLD), and oxidative stress accelerates the progression of NAFLD. Free fatty acids, which are elevated in the liver by obesity or insulin resistance, lead to incomplete oxidation in the mitochondria, peroxisomes, and microsomes, leading to the production of reactive oxygen species (ROS). Among the ROS generated, H2 O2 is mainly produced in peroxisomes and decomposed by catalase. However, when the H2 O2 concentration increases because of decreased expression or activity of catalase, it migrates to cytosol and other organelles, causing cell injury and participating in the Fenton reaction, resulting in serious oxidative stress...
August 17, 2018: Pflügers Archiv: European Journal of Physiology
Idoia Labayen, Jonatan R Ruiz, Lide Arenaza, María Medrano, Ignacio Tobalina, Luis Gracia-Marco, Francisco B Ortega, Beatriz Rodriguez-Vigil
OBJECTIVES: To examine the influence of non-alcoholic fatty liver disease (NAFLD) and hepatic fat content on bone mineral density (BMD), and to investigate whether the relationship between NAFLD and BMD is independent of lifestyle factors related to BMD. METHODS: Hepatic fat content (magnetic resonance imaging), BMD, lean mass index, total and abdominal fat mass (dual-energy-X-ray absorptiometry), moderate to vigorous physical activity (MVPA) (accelerometry), and calcium and vitamin D intake (two 24 h recalls) were measured in 115 children with overweight/obesity aged 10...
August 6, 2018: Pediatric Research
Valerio Nobili, Anna Alisi, Zhipeng Liu, Tiebing Liang, Annalisa Crudele, Massimiliano Raponi, Jingmei Lin, Naga P Chalasani, Wanqing Liu
BACKGROUND: FADS1 gene encodes delta 5 desaturase, a rate-limiting enzyme in the metabolism of n-3 and n-6 polyunsaturated fatty acids (PUFAs). Minor alleles of FADS1 locus polymorphisms are associated with reduced FADS1 expression and intra-hepatic fat accumulation. However, the relationship between FADS1 expression and pediatric nonalcoholic fatty liver disease (NAFLD) risk remains to be explored. METHODS: We analyzed FADS1 transcription levels and their association with intra-hepatic fat and histology in children, and we performed pathway enrichment analysis on transcriptomic profiles associated with FADS1 polymorphisms...
August 4, 2018: Pediatric Research
Yi Luo, Abdul Oseini, Robert Gagnon, Edgar D Charles, Kurex Sidik, Robert Vincent, Rebeca Collen, Michael Idowu, Melissa J Contos, Faridoddin Mirshahi, Kalyani Daita, Amon Asgharpour, Mohammed S Siddiqui, Gabor Jarai, Glenn Rosen, Rose Christian, Arun J Sanyal
Fibrosis, resulted from the imbalance of fibrogenesis and fibrolysis, is a key readout of disease progression in nonalcoholic steatohepatitis (NASH) and reflects mortality risk. Non-invasive biomarkers capable of diagnosing fibrosis stages and monitoring fibrosis changes in NASH patients are urgently needed. This study is to evaluate collagen formation and degradation biomarkers, reflective of fibrogenesis or fibrolysis, in patients with biopsy proven NASH. Collagen formation biomarker PRO-C3 and PRO-C6 levels were significantly higher in patients with advanced fibrosis stage 3-4 than those with fibrosis stage 0-2...
August 17, 2018: Scientific Reports
Grace Hatton, Tommaso Alterio, Valerio Nobili, Jake P Mann
Paediatric non-alcoholic fatty liver disease (NAFLD) is common disorder that has complex pathophysiology and unquantified clinical significance. Though there have been major advances in the field there is much yet to be understood. Areas covered: PubMed/MEDLINE and Embase were searched for articles related to paediatric NAFLD and non-alcoholic steatohepatitis between January 1998 and January 2018. The areas considered to be "unmet needs" were: The relationship between the intestinal microbiome and perinatal events; clinical event risk stratification; and mechanisms underlying portal inflammation...
August 17, 2018: Expert Review of Gastroenterology & Hepatology
Laura J den Hartigh, Leela Goodspeed, Shari A Wang, Heidi L Kenerson, Mohamed Omer, Kevin D O'Brien, Warren Ladiges, Raymond Yeung, Savitha Subramanian
NEW FINDINGS: What is the central question of this study? Whether chronic oral rapamycin promotes beneficial effects on glucose/lipid metabolism and energy balance when administered to mice with an obesogenic diet rich in saturated fat and sucrose has not been explored. What is the main finding and its importance? Chronic oral rapamycin reduces body weight and fat gain, improves insulin sensitivity, and reduces hepatic steatosis when administered to mice with a high fat high sucrose diet...
August 16, 2018: Experimental Physiology
Mingnuan Han, Ting Zhang, Wen Gu, Xingxin Yang, Ronghua Zhao, Jie Yu
Previous studies have suggested that 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) prevents progression of non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet. The present study aimed to evaluate whether TSG could reverse NAFLD induced by a methionine and choline-deficient (MCD) diet and identify the possible mechanism of action. C57BL6/J mice were fed a MCD diet and were treated with TSG, fenofibrate, and resveratrol for 9 weeks. Regulatory effects of several cytokines and enzymes, including Nod-like receptor protein 3, apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), caspase-1, interleukin (IL)-18, IL-1β, and gut microbiota balance were investigated...
August 2018: Experimental and Therapeutic Medicine
Helmut K Seitz, Ramon Bataller, Helena Cortez-Pinto, Bin Gao, Antoni Gual, Carolin Lackner, Philippe Mathurin, Sebastian Mueller, Gyongyi Szabo, Hidekazu Tsukamoto
Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease worldwide. ALD can progress from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which is characterized by hepatic inflammation. Chronic ASH can eventually lead to fibrosis and cirrhosis and in some cases hepatocellular cancer (HCC). In addition, severe ASH (with or without cirrhosis) can lead to alcoholic hepatitis, which is an acute clinical presentation of ALD that is associated with liver failure and high mortality...
August 16, 2018: Nature Reviews. Disease Primers
Cho-Rong Bae, Jun Hino, Hiroshi Hosoda, Mikiya Miyazato, Kenji Kangawa
AIMS: Our previous study revealed that mice transgenic for endothelial-cell-specific overexpression of CNP (E-CNP Tg mice) are protected against the increased fat weight, inflammation, and insulin resistance associated with high-fat diet (HFD)-induced obesity. In addition, E-CNP overexpression prevented abnormal lipid profiles and metabolism and blocked inflammation in the livers of HFD-fed mice. Because obesity, dyslipidemia, and insulin resistance increase the risk of various liver diseases, including non-alcoholic steatohepatitis (NASH), we here studied the role of E-CNP overexpression in the livers of mice in which NASH was induced through feeding of either HFD or a choline-deficient defined l‑amino-acid diet (CDAA)...
August 13, 2018: Life Sciences
Nicolas Perez Gonzalez, Jiaxiang Tao, Nash D Rochman, Dhruv Vig, Denis Wirtz, Sean X Sun
Animal cells use an unknown mechanism to control their growth and physical size. Here, using the fluorescence exclusion method, we quantitatively measure cell volume for adherent cells on substrates of varying stiffness. We discover that the cell volume has a complex dependence on substrate stiffness, and is positively correlated with the size of the cell adhesion to the substrate. From a mechanical force balance condition that determines the geometry of the cell surface, we find that the observed cell volume variation can be quantitatively predicted from the distribution of active myosin throughout the cell cortex...
August 16, 2018: Molecular Biology of the Cell
Brett R Loman, Diego Hernández-Saavedra, Ruopeng An, R Scott Rector
Context: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent and underdiagnosed comorbidity of many chronic diseases that is associated with altered intestinal bacterial communities. This association has prompted research into alternative treatments aimed at modulating intestinal microbiota. Given the novelty of these treatments, scarce evidence regarding their effectiveness in clinical populations exists. Objective: This meta-analysis sought to systemically review and quantitatively synthesize evidence on prebiotic, probiotic, and synbiotic therapies for patients with NAFLD in randomized controlled trials...
August 3, 2018: Nutrition Reviews
Dunya Tomic, William W Kemp, Stuart K Roberts
Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent liver disease in the world. It involves a spectrum of conditions from hepatic steatosis to nonalcoholic steatohepatitis and liver fibrosis, and is a major cause of cirrhosis and hepatocellular carcinoma. It is defined by presence of steatosis in 5% of hepatocytes or more in the absence of other causes of fatty liver. The metabolic syndrome is the major known risk factor for NAFLD. Dietary contributors such as high fructose intake and coffee consumption appear to increase and decrease the risk of disease respectively, but these links are unclear...
August 14, 2018: European Journal of Gastroenterology & Hepatology
Jee Sun Jeong, Mee Kyung Kim, Kyung Do Han, Oak Kee Hong, Ki Hyun Baek, Ki Ho Song, Dong Jin Chung, Jung Min Lee, Hyuk Sang Kwon
BACKGROUND: Whether pancreatic steatosis has a local or systemic effect, like ectopic fat of other major organs, remains unknown. Data on the influence of pancreatic steatosis on microvascular complication are rare. Therefore, we investigated the relationship between pancreatic steatosis and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: The attenuation of three pancreatic regions (head, body, and tail) and the spleen (S) in 186 patients with T2DM was measured using non-enhanced computed tomography imaging...
August 9, 2018: Diabetes & Metabolism Journal
Jun Namkung, Ko Eun Shong, Hyeongseok Kim, Chang Myung Oh, Sangkyu Park, Hail Kim
BACKGROUND: Hepatic steatosis is caused by metabolic stress associated with a positive lipid balance, such as insulin resistance and obesity. Previously we have shown the anti-obesity effects of inhibiting serotonin synthesis, which eventually improved insulin sensitivity and hepatic steatosis. However, it is not clear whether serotonin has direct effect on hepatic lipid accumulation. Here, we showed the possibility of direct action of serotonin on hepatic steatosis. METHODS: Mice were treated with para-chlorophenylalanine (PCPA) or LP-533401 to inhibit serotonin synthesis and fed with high fat diet (HFD) or high carbohydrate diet (HCD) to induce hepatic steatosis...
April 25, 2018: Diabetes & Metabolism Journal
Vladimir J Lozanovski, Elias Khajeh, Hamidreza Fonouni, Jan Pfeiffenberger, Rebecca von Haken, Thorsten Brenner, Markus Mieth, Peter Schirmacher, Christoph W Michalski, Karl Heinz Weiss, Markus W Büchler, Arianeb Mehrabi
INTRODUCTION: Numerous extended donor criteria (EDC) have been identified in liver transplantation (LT), but different EDC have different impacts on graft and patient survival. This study aimed to identify major EDC (maEDC) that were best able to predict the outcome after LT and to examine the plausibility of an allocation algorithm based on these criteria. METHODS: All consecutive LTs between 12/2006 and 03/2014 were included (n = 611). We analyzed the following EDC: donor age > 65 years, body mass index > 30, malignancy and drug abuse history, intensive care unit stay/ventilation > 7 days, aminotransferases > 3 times normal, serum bilirubin > 3 mg/dL, serum Na+ > 165 mmol/L, positive hepatitis serology, biopsy-proven macrovesicular steatosis (BPS) > 40%, and cold ischemia time (CIT) > 14 h...
August 15, 2018: Langenbeck's Archives of Surgery
M Sarkar, N Terrault, C C Duwaerts, P Tien, M I Cedars, H Huddleston
Polycystic Ovary Syndrome (PCOS) affects 10-15% of reproductive age women and is a recognized risk factor for nonalcoholic fatty liver disease (NAFLD). The more severe form of NAFLD, known as nonalcoholic steatohepatitis (NASH), results in liver inflammation with or without fibrosis, and is now a leading cause of cirrhosis. Ethnic differences are apparent in NAFLD, with higher prevalence in Hispanics, although the role of Hispanic ethnicity on risk for NAFLD/NASH in women with PCOS is not known. OBJECTIVE: The aim of this study was to evaluate ethnic differences in the prevalence and risk of NAFLD/NASH in women with PCOS...
February 20, 2018: Current opinion in gynecology and obstetrics
Shanhong Lu, Ting Zhang, Wen Gu, Xingxin Yang, Jianmei Lu, Ronghua Zhao, Jie Yu
Background: The dried mature fruit of Amomum villosum has been historically used in China as food and in the auxiliary treatment of digestive system disorders. Numerous studies have shown that gastrointestinal function is closely related to the development of nonalcoholic fatty liver disease via the "gut-liver" axis. Objective: The present study aimed to explore whether the mechanism underlying the regulation of lipid accumulation in nonalcoholic fatty liver disease (NAFLD) may affect related disorders using the active ingredients in A...
2018: BioMed Research International
Ching-Chou Tsai, Yu-Ju Lin, Hong-Ren Yu, Jiunn-Ming Sheen, You-Lin Tain, Li-Tung Huang, Mao-Meng Tiao
Prenatal exposure to glucocorticoids is associated with negative health consequences for the offspring that persist into adulthood, including liver steatosis. Melatonin has previously been demonstrated to suppress liver steatosis and oxidative stress in humans with non-alcoholic fatty liver disease and in animal models of obesity. The present study aimed to determine whether melatonin protects against liver steatosis induced by prenatal dexamethasone exposure followed by postnatal high-fat diet. Pregnant Sprague-Dawley rats at gestational days 14-21 were administered dexamethasone (0...
August 2018: Experimental and Therapeutic Medicine
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