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In vitro NAFLD

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https://www.readbyqxmd.com/read/27901086/glycycoumarin-inhibits-hepatocyte-lipoapoptosis-through-activation-of-autophagy-and-inhibition-of-er-stress-gsk-3-mediated-mitochondrial-pathway
#1
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
#2
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
#3
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
#4
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...
November 22, 2016: 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27756894/altered-microrna-9-expression-level-is-directly-correlated-with-pathogenesis-of-nonalcoholic-fatty-liver-disease-by-targeting-onecut2-and-sirt1
#12
Ran Ao, Ying Wang, Jing Tong, Bai-Fang Wang
BACKGROUND MicroRNA-9 (miR-9) was detected in nonalcoholic fatty liver disease (NAFLD) patients to understand the role of miR-9 in NAFLD development. MATERIAL AND METHODS Between February 2014 and February 2015, 105 cases of NAFLD were recruited and confirmed by liver biopsy pathology, including patients with mild NAFLD (n=58) and moderate-severe NAFLD (n=47); nonalcoholic steatohepatitis (NASH) (n=53) and non-NASH (n=52); and 50 healthy participants were regarded as the healthy control group. MiR-9 expression was measured by qRT-PCR...
October 19, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27756518/intracellular-and-extracellular-mirnome-deregulation-in-cellular-models-of-nafld-or-nash-clinical-implications
#13
S Di Mauro, M Ragusa, F Urbano, A Filippello, A Di Pino, A Scamporrino, A Pulvirenti, A Ferro, A M Rabuazzo, M Purrello, F Purrello, S Piro
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD has the potential to progress through the inflammatory phase of nonalcoholic steatohepatitis (NASH) to fibrosis, cirrhosis, and hepatocellular carcinoma. Identifying patients at risk for this transition is a relevant clinical challenge. The complexity of these phenotypes in vivo made necessary the development of in vitro models in order to dissect the molecular signalling affected in NAFLD and NASH, but also to identify potential circulating biomarkers...
December 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27686615/precision-medicine-in-alcoholic-and-nonalcoholic-fatty-liver-disease-via-modulating-the-gut-microbiota
#14
REVIEW
Sena Bluemel, Brandon Williams, Rob Knight, Bernd Schnabl
Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) represent a major health burden in industrialized countries. Although alcohol abuse and nutrition play a central role in disease pathogenesis, preclinical models support a contribution of the gut microbiota to ALD and NAFLD. This review describes changes in the intestinal microbiota compositions related to ALD and NAFLD. Findings from in vitro, animal, and human studies are used to explain how intestinal pathology contributes to disease progression...
December 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27658958/erk-dependent-mtor-pathway-is-involved-in-berberine-induced-autophagy-in-hepatic-steatosis
#15
Qin He, Dan Mei, Sha Sha, Shanshan Fan, Lin Wang, Ming Dong
Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem and is considered as a hepatic manifestation of metabolic syndrome. Increasing evidence demonstrates that berberine (BBR), a natural plant alkaloid, is beneficial for obesity-associated NAFLD. However, the mechanisms about how BBR improves hepatic steatosis remain uncertain. Recently, some reports revealed that enhanced autophagy could decrease hepatic lipid accumulation. In this study, we first established a high-fed diet (HFD) mice model and oleate-palmitate-induced lipotoxicity hepatocytes to explore the association among BBR, autophagy and hepatic steatosis...
November 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27613163/resveratrol-supplement-inhibited-the-nf-%C3%AE%C2%BAb-inflammation-pathway-through-activating-ampk%C3%AE-sirt1-pathway-in-mice-with-fatty-liver
#16
Yueli Tian, Jingting Ma, Wudong Wang, Lingjuan Zhang, Jia Xu, Kai Wang, Dongfu Li
Nonalcoholic fatty liver disease (NAFLD) is characterized by high levels of nonesterified fatty acids (NEFA), inflammation, and hepatic steatosis. Inflammation plays a crucial role in the development of fatty liver. Resveratrol (RSV) supplement could improve inflammatory response and hepatic steatosis, whereas the underlying mechanism was not well understood. In this study, mice fed with high-fat diet (HFD) exhibited severe hepatic injury and high blood concentrations of the inflammatory cytokines TNF-α, IL-6, and IL-1β...
November 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27449657/early-steatohepatitis-in-hyperlipidemic-mice-with-endothelial-specific-gain-of-trpc3-function-precedes-changes-in-aortic-atherosclerosis
#17
Kathryn Smedlund, Prabhatachandra Dube, Guillermo Vazquez
Nonalcoholic fatty liver disease (NAFLD) and its more advanced form nonalcoholic steatohepatitis (NASH) are the most common chronic liver diseases in developed countries. Moreover, NAFLD and NASH are considerable risk factors for atherosclerosis, the most frequent vascular pathology in these and other metabolic diseases. Despite this strong connection, current knowledge of the relationship between NAFLD/NASH and atherosclerosis is scarce. Recently, we studied hyperlipidemic Apoe knockout mice with endothelial-specific gain of transient receptor potential canonical 3 channel function (TgESTRPC3/ApoeKO) and found that these animals had increased burden of advanced aortic atherosclerosis (16 wk on high-fat diet) compared with nontransgenic ApoeKO littermate controls (non-Tg/ApoeKO), whereas early lesions (10 wk on high-fat diet) were not different...
August 1, 2016: Physiological Genomics
https://www.readbyqxmd.com/read/27438910/fenofibrate-nanoliposome-preparation-and-its-inhibitory-effects-on-nonalcoholic-fatty-liver-disease-in-mice
#18
Yini Cao, Lu Xu, Cong Chen, Yunan Wang, Qiang Zhang, Rong Qi
The aim was to prepare fenofibrate nanoliposome (FNB-Nanolipo) and investigate its characterizations, oral pharmacokinetic (PK) profiles as well as preventive and therapeutic effects on nonalcoholic fatty liver disease (NAFLD) induced by a methionine choline deficient (MCD) diet in mice. The prepared FNB-Nanolipo showed high drug loading capacity and sustained in vitro FNB release profile. Compared to FNB crude drug at equal doses, the FNB-Nanolipo given at 20 mg/kg/day (beginning on the same day when the MCD diet feeding started and lasted for 7 days) or 40 mg/kg/day (beginning after 7 days of the MCD diet feeding and lasting for another 7 days together with the MCD diet) increased plasma FNB concentration of the mice by 11...
November 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27438262/investigating-nonalcoholic-fatty-liver-disease-in-a-liver-on-a-chip-microfluidic-device
#19
Manuele Gori, Maria Chiara Simonelli, Sara Maria Giannitelli, Luca Businaro, Marcella Trombetta, Alberto Rainer
BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease worldwide, ranging from simple steatosis to nonalcoholic steatohepatitis, which may progress to cirrhosis, eventually leading to hepatocellular carcinoma (HCC). HCC ranks as the third highest cause of cancer-related death globally, requiring an early diagnosis of NAFLD as a potential risk factor. However, the molecular mechanisms underlying NAFLD are still under investigation. So far, many in vitro studies on NAFLD have been hampered by the limitations of 2D culture systems, in which cells rapidly lose tissue-specific functions...
2016: PloS One
https://www.readbyqxmd.com/read/27435856/fgf21-ameliorates-nonalcoholic-fatty-liver-disease-by-inducing-autophagy
#20
Shenglong Zhu, Yunzhou Wu, Xianlong Ye, Lei Ma, Jianying Qi, Dan Yu, Yuquan Wei, Guangxiao Lin, Guiping Ren, Deshan Li
The aim of this study is to evaluate the role of fibroblast growth factor 21 (FGF21) in nonalcoholic fatty liver disease (NAFLD) and seek to determine if its therapeutic effect is through induction of autophagy. In this research, Monosodium L-glutamate (MSG)-induced obese mice or normal lean mice were treated with vehicle, Fenofibrate, and recombinant murine FGF21, respectively. After 5 weeks of treatment, metabolic parameters including body weight, blood glucose and lipid levels, hepatic and fat gene expression levels were monitored and analyzed...
September 2016: Molecular and Cellular Biochemistry
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