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Non-alcoholic steatosis

Kwang-Youn Kim, Hyun-Jun Jang, Yong Ryul Yang, Kwang-Il Park, JeongKon Seo, Il-Woo Shin, Tae-Il Jeon, Soon-Cheol Ahn, Pann-Ghill Suh, Timothy F Osborne, Young-Kyo Seo
Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride...
October 21, 2016: Scientific Reports
Han-Sol Park, Jung Eun Jang, Myoung Seok Ko, Sung Hoon Woo, Bum Joong Kim, Hyun Sik Kim, Hye Sun Park, In-Sun Park, Eun Hee Koh, Ki-Up Lee
BACKGROUND: Non-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO) and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH), but underlying mechanisms of this prevention are largely unknown...
October 2016: Diabetes & Metabolism Journal
Zi Lin, Zheng-Feng Wu, Cui-Hua Jiang, Qing-Wen Zhang, Sheng Ouyang, Chun-Tao Che, Jian Zhang, Zhi-Qi Yin
BACKGROUND: Hepatic steatosis (HS) is the early stage of nonalcoholic fatty liver disease which is caused by impaired hepatic lipid homeostasis. Cyclocarya paliurus, an herbal tea consumed in China, has been demonstrated to ameliorate abnormal lipid metabolism for the treatment of metabolic diseases. PURPOSE: We aimed to investigate the regulative effect of chloroform extract from Cyclocarya paliurus (ChE) on treatment of HS, as well as key factors involved in hepatic lipid metabolism...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Su Jin Lee, Jeong Han Kang, Da Eun Lee, Min Jeong Nam, Hyun-Shik Lee, Oh-Shin Kwon
Chronic alcohol consumption causes hepatic steatosis, which is characterized by a considerable increase in free fatty acid (FFA) and triglyceride levels. To identify the possible proteins involved in the progression to alcoholic hepatosteatosis, we performed proteomic analysis on livers of mice exposed to alcohol. 2D-based proteomic analysis revealed that EtOH exposure in mice changed the expression of 43 proteins compared with that in mice fed a normal diet (ND). The most notable protein changes were proteins involved in Met metabolism and oxidative stress, most of which were significantly downregulated in alcohol-exposed animals...
October 20, 2016: Journal of Cellular Biochemistry
R Jin, A Krasinskas, N-A Le, J V Konomi, J Holzberg, R Romero, M B Vos
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of the endogenous fibrinolytic system and is known to be increased in obesity, insulin resistance and non-alcoholic fatty liver disease (NAFLD). We previously demonstrated that PAI-1 levels were closely related to the amount of hepatic steatosis in children. OBJECTIVES: The aim of this study was to characterize plasma PAI-1 in relationship to severity of inflammation and fibrosis, as well as to plasma lipids in children with NAFLD...
October 20, 2016: Pediatric Obesity
Thomas Gilliland, Sylvie Dufour, Gerald I Shulman, Kitt Falk Petersen, Sukru H Emre
NAFLD is a common condition linked to obesity, type 2 diabetes, and metabolic syndrome. Simple hepatic steatosis is a risk factor for inflammatory reactions in the liver (NASH), which may lead to cirrhosis. While the mechanism is unclear, NAFLD and NASH are associated with panhypopituitarism, which in the pediatric population often results from craniopharyngioma or pituitary adenoma and the sequelae of treatment, causing hypothyroidism, adrenal insufficiency, hypogonadotropic hypogonadism, and GH deficiency...
October 20, 2016: Pediatric Transplantation
Jennie Ka Ching Lau, Xiang Zhang, Jun Yu
Non-alcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. NAFLD progresses from simple liver steatosis to non-alcoholic steatohepatitis (NASH) and in more severe cases to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Due to its growing worldwide prevalence, various animal models that mirror both the histopathology and pathophysiology of each stage of human NAFLD have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field...
October 18, 2016: Journal of Pathology
Gretchen Bain, Kristen E Shannon, Fei Huang, Janice Darlington, Lance Goulet, Patricia Prodanovich, Gina L Ma, Angelina M Santini, Adam J Stein, Dave Lonergan, Christopher D King, Imelda Calderon, Andiliy Lai, John H Hutchinson, Jilly F Evans
Autotaxin (ATX) is a secreted glycoprotein that converts lysophosphatidylcholine (LPC) to the bioactive phospholipid lysophosphatidic acid (LPA) and is the major enzyme generating circulating LPA. Inhibition of LPA signaling has profound anti-fibrotic effects in multiple organ systems including the lung, kidney, skin and peritoneum. However, other LPA-generating pathways exist and the role of ATX in localized tissue LPA production and fibrosis remains unclear and controversial. In this study, we describe the preclinical pharmacological, pharmacokinetic and pharmacodynamic properties of a novel small-molecule ATX inhibitor [3-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl) thio)-2-fluorobenzoic acid sodium salt] (PAT-505)...
October 17, 2016: Journal of Pharmacology and Experimental Therapeutics
Malleswarapu Mahesh, Munugala Bharathi, Mooli Raja Gopal Reddy, Manchiryala Sravan Kumar, Uday Kumar Putcha, Ayyalasomayajula Vajreswari, Shanmugam M Jeyakumar
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks...
September 2016: Preventive Nutrition and Food Science
Terry D Hinds, Katherine A Burns, Peter A Hosick, Lucien McBeth, Andrea Nestor-Kalinoski, Heather A Drummond, Adbulhadi A AlAmodi, Michael W Hankins, John P Vanden Heuvel, David E Stec
Non-alcoholic fatty liver disease (NAFLD) is the most rapidly growing form of liver disease, and if left untreated can result in non-alcoholic steatohepatitis (NASH) ultimately resulting in liver cirrhosis and failure. Biliverdin reductase-A (BVRA) is a multi-functioning protein primarily responsible for the reduction of biliverdin to bilirubin. Also, BVRA can function as a kinase and transcription factor, regulating several cellular functions. We report here that liver BVRA protects against hepatic steatosis by inhibiting glycogen synthase kinase-3β (GSK3β) by enhancing serine 9 phosphorylation, which inhibits its activity...
October 10, 2016: Journal of Biological Chemistry
Jennifer Chi Lo, Anne E O'Connor, Zane B Andrews, Camden Lo, Tony Tiganis, Matthew J Watt, Moira K O'Bryan
Fatty liver, or hepatic steatosis, is an alarmingly common pathology in western societies, in large part because if left unheaded it can lead to life-threatening forms of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. As such, it is essential that we attain a greater understanding of the pathways that control energy partitioning in the liver, and ultimately how they are impacted by environmental factors. Herein, we define the essential requirement for a member of the RAB-like clade of small GTPases, RABL2, in fatty acid metabolism including in microtubule-associated mitochondrial movement within the liver...
October 12, 2016: Endocrinology
J E Nelson, P Handa, B Aouizerat, L Wilson, L A Vemulakonda, M M Yeh, K V Kowdley
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). AIM: To investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort. METHODS: A total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563...
October 11, 2016: Alimentary Pharmacology & Therapeutics
Hyunwoo Oh, Dae Won Jun, Waqar K Saeed, Mindie H Nguyen
The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 25-30% of the population, and is the most common cause of elevated liver enzymes in Korea. NAFLD is a "hot potato" for pharmaceutical companies. Many clinical trials are underway to develop a first-in-class drug to treat NAFLD. However, there are several challenging issues regarding the diagnosis of NAFLD. Currently, liver biopsy is the gold standard method for the diagnosis of NAFLD and steatohepatitis. Ideally, globally recognized standards for histological diagnosis and methods to optimize observer agreement on biopsy interpretation should be developed...
September 2016: Clinical and Molecular Hepatology
Ali Canbay, Jan-Peter Sowa, Wing-Kin Syn, Jürgen Treckmann
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a continuously increasing cause of chronic liver disease and a health burden in all populations affected by the obesity and metabolic syndrome pandemic. Cirrhotic alterations or hepatocellular carcinoma developing from NAFLD may require liver transplantation (LTx). METHODS: Current literature was screened for data on LTx in the setting of NAFLD. RESULTS: NAFLD-associated LTx is expected to increase in number and relevance during the next decade...
August 2016: Visc Med
Ilaria Croci, Nuala M Byrne, Veronique S Chachay, Andrew P Hills, Andrew D Clouston, Trisha M O'Moore-Sullivan, Johannes B Prins, Graeme A Macdonald, Ingrid J Hickman
AIM: To investigate the independent effects of 6-mo of dietary energy restriction or exercise training on whole-body and hepatic fat oxidation of patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Participants were randomised into either circuit exercise training (EX; n = 13; 3 h/wk without changes in dietary habits), or dietary energy restriction (ER) without changes in structured physical activity (ER; n = 8). Respiratory quotient (RQ) and whole-body fat oxidation rates (Fatox) were determined by indirect calorimetry under basal, insulin-stimulated and exercise conditions...
September 28, 2016: World Journal of Hepatology
M Maida, F S Macaluso, F Salomone, S Petta
NAFLD (Non-Alcoholic Fatty Liver Disease) is an increasingly significant public health issue, regarded as the most relevant liver disease of the twenty-first century. Approximately 20%-30% of NAFLD subjects develop a NASH (Non-Alcoholic Steato-Hepatitis), a condition which can potentially evolve to liver cirrhosis and hepatocellular carcinoma. For these reasons a proper evaluation of liver damage is a key point for diagnosis and prognosis and liver biopsy still remains the "gold standard" procedure both for discrimination between steatosis and steatohepatitis and assessment of the degree of liver fibrosis...
October 4, 2016: Current Molecular Medicine
Caroline Duval, Fatima Teixeira-Clerc, Alix F Leblanc, Sothea Touch, Claude Emond, Michèle Guerre-Millo, Sophie Lotersztajn, Robert Barouki, Martine Aggerbeck, Xavier Coumoul
BACKGROUND: Exposure to persistent organic pollutants (POPs) has been associated with the progression of chronic liver diseases, yet the contribution of POPs to the development of fibrosis in non-alcoholic fatty liver disease (NAFLD), a condition closely linked to obesity, remains poorly documented. OBJECTIVES: We investigated the effects of subchronic exposure to low-doses of the POP 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor ligand, on NAFLD progression in diet-induced obese C57BL/6J mice...
October 7, 2016: Environmental Health Perspectives
Hiroyuki Nakashima, Masahiro Nakashima, Manabu Kinoshita, Masami Ikarashi, Hiromi Miyazaki, Hiromi Hanaka, Junko Imaki, Shuhji Seki
We have recently reported that Kupffer cells consist of two subsets, radio-resistant resident CD68+ Kupffer cells and radio-sensitive recruited CD11b+ Kupffer cells/macrophages (Mφs). Non-alcoholic steatohepatitis (NASH) is characterized not only by hepatic steatosis but also chronic inflammation and fibrosis. In the present study, we investigated the immunological mechanism of diet-induced steatohepatitis in fibroblast growth factor 5 (FGF5) deficient mice. After consumption of a high fat diet (HFD) for 8 weeks, FGF5 null mice developed severe steatohepatitis and fibrosis resembling human NASH...
October 6, 2016: Scientific Reports
Maëna Le Corvec, Coralie Allain, Salim Lardjane, Thibault Cavey, Bruno Turlin, Alain Fautrel, Karima Begriche, Valérie Monbet, Bernard Fromenty, Patricia Leroyer, Pascal Guggenbuhl, Martine Ropert, Olivier Sire, Olivier Loréal
Non-alcoholic fatty liver disease is associated with obesity, diabetes, and metabolic syndrome. The detection of systemic metabolic changes associated with alterations in the liver status during non-alcoholic fatty liver disease could improve patient follow-up. The aim of the present study was to evaluate the potential of mid-infrared fibre evanescent wave spectroscopy as a minimum-invasive method for evaluating the liver status during non-alcoholic fatty liver disease. Seventy-five mice were subjected to a control, high-fat or high-fat-high carbohydrate diets...
September 26, 2016: Analyst
Ahmed Abd Allah Salman, Soheir Abd Elfattah Aboelfadl, Mona Abd Elmenem Heagzy
BACKGROUND: Liver histology remains the gold standard for assessing non-alcoholic fatty liver disease (NAFLD). Noninvasive serological markers and radiological methods have been developed to evaluate steatosis to avoid biopsy. AIM: To put cutoff value for liver enzymes that could predict non-alcoholic steatohepatitis (NASH). PATIENTS AND METHODS: This study was conducted on 54 patients (with NAFLD diagnosed by the US). Patients were subjected to history, physical, anthropometric measurements, investigations including liver enzymes, abdominal US, and liver biopsy...
September 15, 2016: Open Access Macedonian Journal of Medical Sciences
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