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In vitro NAFLD

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https://www.readbyqxmd.com/read/28098838/role-of-udp-glucuronosyltransferase-1a1-in-the-metabolism-and-pharmacokinetics-of-silymarin-flavonolignans-in-patients-with-hcv-and-nafld
#1
Ying Xie, Sonia R Miranda, Janelle M Hoskins, Roy L Hawke
Silymarin is the most commonly used herbal medicine by patients with chronic liver disease. Silymarin flavonolignans undergo rapid first-pass metabolism primarily by glucuronidation. The aims of this investigation were: (1) to determine the association of UGT1A1*28 polymorphism with the area under the plasma concentration-time curves (AUCs) for silybin A (SA) and silybin B (SB); (2) to evaluate the effect of UGT1A1*28 polymorphism on the profile of flavonolignan glucuronide conjugates found in the plasma; and (3) to investigate the role of UGT1A1 enzyme kinetics on the pharmacokinetics of SA and SB...
January 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28081181/aronia-melanocarpa-extract-ameliorates-hepatic-lipid-metabolism-through-ppar%C3%AE-2-downregulation
#2
Chung-Hwa Park, Jung-Hee Kim, Eun Byul Lee, Wonhee Hur, Oh-Joo Kwon, Hyoung-Jin Park, Seung Kew Yoon
Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Studies have demonstrated that anthocyanin-rich foods may improve hyperlipidemia and ameliorate hepatic steatosis. Here, effects of Aronia melanocarpa (AM), known to be rich of anthocyanins, on hepatic lipid metabolism and adipogenic genes were determined. AM was treated to C57BL/6N mice fed with high fat diet (HFD) or to FL83B cells treated with free fatty acid (FFA). Changes in levels of lipids, enzymes and hormones were observed, and expressions of adipogenic genes involved in hepatic lipid metabolism were detected by PCR, Western blotting and luciferase assay...
2017: PloS One
https://www.readbyqxmd.com/read/28077733/identification-of-potential-plasma-biomarkers-for-nonalcoholic-fatty-liver-disease-by-integrating-transcriptomics-and-proteomics-in-laying-hens
#3
Meng-Tsz Tsai, Yu-Jen Chen, Ching-Yi Chen, Mong-Hsun Tsai, Chia-Li Han, Yu-Ju Chen, Harry J Mersmann, Shih-Torng Ding
BACKGROUND: Prevalent worldwide obesity is associated with increased incidence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. The identification of noninvasive biomarkers for NAFLD is of recent interest. Because primary de novo lipogenesis occurs in chicken liver as in human liver, adult chickens with age-associated steatosis resembling human NAFLD is an appealing animal model. OBJECTIVE: The objective of this study was to screen potential biomarkers in the chicken model for NAFLD by transcriptomic and proteomic analysis...
January 11, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28030556/hepatocyte-hypoxia-inducible-factor-1-mediates-the-development-of-liver-fibrosis-in-a-mouse-model-of-nonalcoholic-fatty-liver-disease
#4
Omar A Mesarwi, Mi-Kyung Shin, Shannon Bevans-Fonti, Christina Schlesinger, Janet Shaw, Vsevolod Y Polotsky
BACKGROUND: Obstructive sleep apnea (OSA) is associated with the progression of non-alcoholic fatty liver disease (NAFLD) to steatohepatitis and fibrosis. This progression correlates with the severity of OSA-associated hypoxia. In mice with diet induced obesity, hepatic steatosis leads to liver tissue hypoxia, which worsens with exposure to intermittent hypoxia. Emerging data has implicated hepatocyte cell signaling as an important factor in hepatic fibrogenesis. We hypothesized that hepatocyte specific knockout of the oxygen sensing α subunit of hypoxia inducible factor-1 (HIF-1), a master regulator of the global response to hypoxia, may be protective against the development of liver fibrosis...
2016: PloS One
https://www.readbyqxmd.com/read/28027586/targeting-the-mitochondrial-pyruvate-carrier-attenuates-fibrosis-in-a-mouse-model-of-nonalcoholic-steatohepatitis
#5
Kyle S McCommis, Wesley T Hodges, Elizabeth M Brunt, ILKe Nalbantoglu, William G McDonald, Christopher Holley, Hideji Fujiwara, Jean E Schaffer, Jerry R Colca, Brian N Finck
: Diseases of the liver related to metabolic syndrome have emerged as the most common and undertreated hepatic ailments. The cause of nonalcoholic fatty liver disease (NAFLD) is the aberrant accumulation of lipid in hepatocytes, though the mechanisms whereby this leads to hepatocyte dysfunction, death, and hepatic fibrosis are still unclear. Insulin-sensitizing thiazolidinediones have shown efficacy in treating nonalcoholic steatohepatitis (NASH), but their widespread use is constrained by dose-limiting side effects thought to be due to activation of the peroxisome proliferator-activated receptor γ (PPARγ)...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27996362/the-effects-of-di-2-ethyl-hexyl-phthalate-dehp-on-cellular-lipid-accumulation-in-hepg2-cells-and-its-potential-mechanisms-in-the-molecular-level
#6
Wang Zhang, Xin-Yue Shen, Wen-Wen Zhang, Hao Chen, Wei-Ping Xu, Wei Wei
Diethylhexyl phthalate (DEHP) is suspected to be an inevitable factor related to metabolic disease. Our previous study demonstrated that excess DEHP could exacerbate Non Alcoholic Fatty Liver Disease(NAFLD) in SD rats. Addressing the terra incognita in DEHP-induced metabolic dysfunction, this study used HepG2 cells to investigate the potential mechanisms involved in DEHP-induced toxicity in vitro. The cells were established lipid overload model with oleic acid and BSA, then exposed to different concentrations (5, 10, 25, 50, 100 μmol/l DEHP) of DEHP for further analysis...
December 20, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27981809/chicoric-acid-attenuate-a-nonalcoholic-steatohepatitis-by-inhibiting-key-regulators-of-lipid-metabolism-fibrosis-oxidation-and-inflammation-in-mice-with-methionine-and-choline-deficiency
#7
Myungsuk Kim, GyHye Yoo, Ahmad Randy, Hyoung Seok Kim, Chu Won Nho
SCOPE: Nonalcoholic fatty liver diseases (NAFLD) range histopathologically from hepatic steatosis to steatohepatitis. Chicoric acid has beneficial effects on obesity and liver injury, but its effects on nonalcoholic steatohepatitis (NASH) have not yet been determined. This study examined the effects of Crepidiastrum denticulatum extract (CDE) and its active compound chicoric acid in a mouse model of NASH and fibrosis. METHODS: CDE and chicoric acid were orally administrated to mice fed a methionine- and choline-deficient (MCD) diet...
December 16, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27959408/involvement-of-xanthine-oxidase-and-paraoxonase-1-in-the-process-of-oxidative-stress-in-nonalcoholic-fatty-liver-disease
#8
Bing Wang, Rui-Ning Yang, Yue-Rong Zhu, Ji-Cheng Xing, Xiao-Wei Lou, Yu-Jie He, Qi-Long Ding, Ming-Yue Zhang, Hong Qiu
Xanthine oxidase (XOD) and paraoxonase 1 (PON1) are important enzymes in redox reactions in vivo, and are predominantly synthesized by the liver. The aim of the present study was to investigate the redox state in nonalcoholic fatty liver disease, and determine the association between the activities of XOD and PON1 and the severity of NAFLD. Sprague‑Dawley rats were randomly divided into control, model and α‑lipoic acid (high and low dose) groups. The rats in the NAFLD model were induced by feeding a high fat diet for 12 weeks and the in vitro cell model of hepatocyte steatosis was induced by treating L‑02 cells with oleic acid for 24 h...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27939923/cd98-sirna-loaded-nanoparticles-decrease-hepatic-steatosis-in-mice
#9
Brandon S B Canup, Heliang Song, Vu Le Ngo, Xiangxiao Meng, Timothy L Denning, Pallavi Garg, Hamed Laroui
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid hepatic accumulation. Here, we investigated whether a reduction of CD98 expression mediated by CD98 siRNA-loaded nanoparticles (NPs) could attenuate liver disease markers in a mouse model of NAFLD. NPs were generated using a double emulsion/solvent evaporation technique. Mice fed a high fat diet for 8 weeks to induce fatty liver were treated with vein tail injections of CD98 siRNA-loaded NPs. In vitro, HepG2 treated with CD98 siRNA-loaded NPs showed significant downregulation of CD98 leading to a significant decrease of major pro-inflammatory cytokines and markers...
November 17, 2016: Digestive and Liver Disease
https://www.readbyqxmd.com/read/27901086/glycycoumarin-inhibits-hepatocyte-lipoapoptosis-through-activation-of-autophagy-and-inhibition-of-er-stress-gsk-3-mediated-mitochondrial-pathway
#10
Enxiang Zhang, Shutao Yin, Xinhua Song, Lihong Fan, Hongbo Hu
Herbal medicine as an alternative approach in the treatment of disease has drawn growing attention. Identification of the active ingredient is needed for effective utilization of the herbal medicine. Licorice is a popular herbal plant that is widely used to treat various diseases including liver diseases. Glycycoumarin (GCM) is a representative of courmarin compounds isolated from licorice. In the present study, the protective effect of GCM on hepatocyte lipoapoptosis has been evaluated using both cell culture model of palmitate-induced lipoapoptosis and animal model of non-alcoholic steatohepatitis (NASH)...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895587/vitamin-d-signaling-through-induction-of-paneth-cell-defensins-maintains-gut-microbiota-and-improves-metabolic-disorders-and-hepatic-steatosis-in-animal-models
#11
Danmei Su, Yuanyang Nie, Airu Zhu, Zishuo Chen, Pengfei Wu, Li Zhang, Mei Luo, Qun Sun, Linbi Cai, Yuchen Lai, Zhixiong Xiao, Zhongping Duan, Sujun Zheng, Guihui Wu, Richard Hu, Hidekazu Tsukamoto, Aurelia Lugea, Zhenqui Liu, Stephen J Pandol, Yuan-Ping Han
Metabolic syndrome (MetS), characterized as obesity, insulin resistance, and non-alcoholic fatty liver diseases (NAFLD), is associated with vitamin D insufficiency/deficiency in epidemiological studies, while the underlying mechanism is poorly addressed. On the other hand, disorder of gut microbiota, namely dysbiosis, is known to cause MetS and NAFLD. It is also known that systemic inflammation blocks insulin signaling pathways, leading to insulin resistance and glucose intolerance, which are the driving force for hepatic steatosis...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27893783/role-of-pten-in-oxidative-stress-and-dna-damage-in-the-liver-of-whole-body-pten-haplodeficient-mice
#12
Ezgi Eyluel Bankoglu, Oliver Tschopp, Johannes Schmitt, Philipp Burkard, Daniel Jahn, Andreas Geier, Helga Stopper
Type 2 diabetes (T2DM) and obesity are frequently associated with non-alcoholic fatty liver disease (NAFLD) and with an elevated cancer incidence. The molecular mechanisms of carcinogenesis in this context are only partially understood. High blood insulin levels are typical in early T2DM and excessive insulin can cause elevated reactive oxygen species (ROS) production and genomic instability. ROS are important for various cellular functions in signaling and host defense. However, elevated ROS formation is thought to be involved in cancer induction...
2016: PloS One
https://www.readbyqxmd.com/read/27888103/luteolin-improves-non-alcoholic-fatty-liver-disease-in-db-db-mice-by-inhibition-of-liver-x-receptor-activation-to-down-regulate-expression-of-sterol-regulatory-element-binding-protein-1c
#13
Ye Yin, Lu Gao, Haiyan Lin, Yue Wu, Xiao Han, Yunxia Zhu, Jie Li
In this study, we report that daily administration of luteolin for 8 weeks improved hepatic steatosis by repressing hepatic TG accumulation and increasing glycogen storage. Luteolin inhibited hepatic de novo lipid synthesis by regulating the LXR-SREBP-1c signaling pathway, which is over-activated in the livers of db/db mice. Further in vitro studies revealed that luteolin can competitively bind to the ligand binding domain to suppress the LXR activation induced by an LXR agonist and high glucose, thereby decreasing TG accumulation in HepG2 cells and primary hepatocytes...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27876107/sodium-butyrate-protects-mice-from-the-development-of-the-early-signs-of-non-alcoholic-fatty-liver-disease-role-of-melatonin-and-lipid-peroxidation
#14
Cheng Jun Jin, Anna Janina Engstler, Cathrin Sellmann, Doreen Ziegenhardt, Marianne Landmann, Giridhar Kanuri, Hakima Lounis, Markus Schröder, Walter Vetter, Ina Bergheim
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide with universally accepted treatments still lacking. Oral supplementation of sodium butyrate (SoB) has been suggested to attenuate liver damage of various aetiologies. Our study aimed to further delineate mechanisms involved in the SoB-dependent hepatic protection using a mouse model of fructose-induced NAFLD and in in vitro models. C57BL/6J mice were either pair-fed a fructose-enriched liquid diet ±0·6 g/kg body weight per d SoB or standard chow for 6 weeks...
November 23, 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/27853276/sumo-specific-protease-3-is-a-key-regulator-for-hepatic-lipid-metabolism-in-non-alcoholic-fatty-liver-disease
#15
Yuhan Liu, Fudong Yu, Yan Han, Qing Li, Zhujun Cao, Xiaogang Xiang, Shaowen Jiang, Xiaolin Wang, Jie Lu, Rongtao Lai, Hui Wang, Wei Cai, Shisan Bao, Qing Xie
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes. The role of SENP3 in lipid metabolism, particularly NAFLD, is unclear. Our results showed that hepatic SENP3 was up-regulated in NAFLD patients and an animal model in vivo and after loading hepatocytes with free fatty acids (FFA) in vitro. Intracellular lipid accumulation was determined in SENP3 silenced or overexpressed hepatocytes with/without FFA in vitro. Confirming a role for SENP3, gene silencing was associated in vitro with amelioration of lipid accumulation and overexpression with enhancement of lipid accumulation...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27847552/schisandrin-b-a-double-edged-sword-in-nonalcoholic-fatty-liver-disease
#16
REVIEW
Pou Kuan Leong, Kam Ming Ko
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. The high global prevalence of NAFLD has underlined the important public health implications of this disease. The pathogenesis of NAFLD involves the abnormal accumulation of free fatty acids, oxidative stress, endoplasmic reticulum (ER) stress, and a proinflammatory state in the liver. Schisandrin B (Sch B), an active dibenzooctadiene lignan isolated from the fruit of Schisandra chinensis (a traditional Chinese herb), was found to possess antihyperlipidemic, antioxidant, anti-ER stress, and anti-inflammatory activities in cultured hepatocytes in vitro and in rodent livers in vivo...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27824080/lycium-barbarum-polysaccharide-attenuates-high-fat-diet-induced-hepatic-steatosis-by-up-regulating-sirt1-expression-and-deacetylase-activity
#17
Li Jia, Wang Li, Jianning Li, Yan Li, Hui Song, Yansong Luan, Hui Qi, Lirong Ma, Xiaohong Lu, Yi Yang
In this study, we aimed to investigate the protective effects and underlying mechanism of Lycium barbarum polysaccharide (LBP) on high-fat-induced nonalcoholic fatty liver disease (NAFLD). Recently, sirtuin 1 (SIRT1) has been shown to play an important role in the regulation of hepatocellular lipid metabolism. Here, we demonstrated that LBP up-regulates SIRT1 deacetylase activity and protein expression by enhancing the NAD(+)/NADH ratio. Subsequently, LBP promoted LKB1 deacetylation and AMPK phosphorylation via SIRT1-dependent signalling...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27813270/endoplasmic-reticulum-stress-contributes-to-ferritin-molecules-mediated-macrophage-migration-via-p-selectin-glycoprotein-ligand-1
#18
Chi-Mei Wang, Yue-Hwa Chen, Yu-Chieh Lee, Jung-Su Chang
SCOPE: Obesity is associated with elevated serum ferritin and increased macrophage activation and infiltration; however, the causal mechanisms underlying this relationship remain undefined. METHODS AND RESULTS: Serum ferritin and soluble P-selectin glycoprotein ligand (sPSGL)-1 level were higher in obese adolescents and patients with moderate nonalcoholic fatty liver disease (NAFLD) compared with controls (all p < 0.05). Multivariate linear regression revealed that serum ferritin was independently associated with sPSGL-1 (B = 0...
November 4, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27760195/prolyl-oligopeptidase-inhibition-attenuates-steatosis-in-the-l02-human-liver-cell-line
#19
Da Zhou, Bing-Hang Li, Jing Wang, Yong-Nian Ding, Yan Dong, Yuan-Wen Chen, Jian-Gao Fan
BACKGROUND: Prolyl oligopeptidase (POP) is a serine endopeptidase that is widely distributed in vivo, particularly in the liver. Significant changes in functional mitochondrial proteins involved with mitochondrial oxidoreductases/transporters and nucleic acid binding proteins were observed after POP inhibition in the liver, which suggested a role of POP in regulating liver energy metabolism. Steatosis in nonalcoholic fatty liver disease (NAFLD) is associated with disturbances in lipid and energy metabolism in hepatocytes...
2016: PloS One
https://www.readbyqxmd.com/read/27760050/insulin-receptor-thr1160-phosphorylation-mediates-lipid-induced-hepatic-insulin-resistance
#20
Max C Petersen, Anila K Madiraju, Brandon M Gassaway, Michael Marcel, Ali R Nasiri, Gina Butrico, Melissa J Marcucci, Dongyan Zhang, Abudukadier Abulizi, Xian-Man Zhang, William Philbrick, Stevan R Hubbard, Michael J Jurczak, Varman T Samuel, Jesse Rinehart, Gerald I Shulman
Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D), but whether NAFLD plays a causal role in the pathogenesis of T2D is uncertain. One proposed mechanism linking NAFLD to hepatic insulin resistance involves diacylglycerol-mediated (DAG-mediated) activation of protein kinase C-ε (PKCε) and the consequent inhibition of insulin receptor (INSR) kinase activity. However, the molecular mechanism underlying PKCε inhibition of INSR kinase activity is unknown. Here, we used mass spectrometry to identify the phosphorylation site Thr1160 as a PKCε substrate in the functionally critical INSR kinase activation loop...
November 1, 2016: Journal of Clinical Investigation
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