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In vitro NAFLD

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https://www.readbyqxmd.com/read/28809727/models-of-non-alcoholic-fatty-liver-disease-and-potential-translational-value-the-effects-of-3-5-l-diiodothyronine
#1
Elena Grasselli, Laura Canesi, Piero Portincasa, Adriana Voci, Laura Vergani, Ilaria Demori
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in industrialized countries and is associated with increased risk of cardiovascular, hepatic and metabolic diseases. Molecular mechanisms on the root of the disrupted lipid homeostasis in NAFLD and potential therapeutic strategies can benefit of in vivo and in vitro experimental models of fatty liver. Here, we describe the high fat diet (HFD)-fed rat in vivo model, and two in vitro models, the primary cultured rat fatty hepatocytes or the FaO rat hepatoma fatty cells, mimicking human NAFLD...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28777914/resveratrol-improves-high-fat-diet-induced-fatty-liver-and-insulin-resistance-by-concomitant-inhibiting-proteolytic-cleavage-of-srebps-ffas-oxidation-and-intestinal-tgs-absorption
#2
Eman F Khaleel, Ghada Ahmed Abdel-Aleem, Dalia Gamal Eldin Mostafa
Resveratrol (RES) has the ability to ameliorate non-alcoholic fatty liver disease (NAFLD) and the mechanism remains unclear. Hence, using high-fat diet (HFD) obese rat model, we investigated the effect of low dose of RES (20 mg/kg) on hepatic Sterol regulatory element-binding proteins (SREBPs)-lipogenesis pathway, enzymes involved in β-oxidation and activity of pancreatic lipase. 4 groups of rats (n=8) of either control (12 % of calories as fat) or HFD (40 % of calories as fat), both were administered with either normal saline as vehicle or RES as a concomitant treatment for 8 weeks on a daily basis, orally...
August 4, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28771824/down-regulation-of-lncrna-neat1-alleviated-the-non-alcoholic-fatty-liver-disease-via-mtor-s6k1-signaling-pathway
#3
Xiang Wang
BACKGROUND: Without effective medical interventions for complete reverse of NAFLD, it needs to urgently explore the underlying molecular mechanisms of non-alcoholic fatty liver disease (NAFLD) to offer a novel therapeutic strategy for people suffering from NAFLD. METHODS: Sprague-Dawley (SD) rats were used to establish the NAFLD animal model. Lipofectamine 2000 was used to silence or over-express NEAT1. The expression of NEAT1 and the mRNA levels of ACC and FAS were determined by qRT-PCR...
August 3, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28718838/phyllanthus-niruri-standardized-extract-alleviates-the-progression-of-non-alcoholic-fatty-liver-disease-and-decreases-atherosclerotic-risk-in-sprague-dawley-rats
#4
Raghdaa Hamdan Al Zarzour, Mariam Ahmad, Mohd Zaini Asmawi, Gurjeet Kaur, Mohammed Ali Ahmed Saeed, Majed Ahmed Al-Mansoub, Sultan Ayesh Mohammed Saghir, Nasiba Salisu Usman, Dhamraa W Al-Dulaimi, Mun Fei Yam
Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague-Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC-HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group...
July 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28694658/anti-steatotic-and-anti-fibrotic-effects-of-the-kca3-1-channel-inhibitor-senicapoc-in-non-alcoholic-liver-disease
#5
Latha Paka, David E Smith, Dawoon Jung, Siobhan McCormack, Ping Zhou, Bin Duan, Jing-Song Li, Jiaqi Shi, Yong-Jie Hao, Kai Jiang, Michael Yamin, Itzhak D Goldberg, Prakash Narayan
AIM: To evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD). METHODS: We have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide (TAA) and high fat diet (HFD)-induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis...
June 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28667176/mir-212-5p-suppresses-lipid-accumulation-by-targeting-fas-and-scd1
#6
Yajie Guo, Junjie Yu, Chunxia Wang, Kai Li, Bin Liu, Ying Du, Fei Xiao, Shanghai Chen, Feifan Guo
MicroRNAs, a class of small non-coding RNAs, are implicated in controlling a variety of biological processes. We have shown that leucine deprivation suppresses lipogenesis by inhibiting fatty acid synthase (FAS) expression in the liver previously; the aim of our current study is to investigate which kind of microRNA is involved in the regulation of FAS expression in response to leucine deprivation. Here, we indicated that microRNA-212-5p specifically binds to mouse FAS 3'UTR and inhibits its activity. Leucine deficiency significantly increased the mRNA levels of miR-212-5p in the livers of mice...
June 30, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28630632/erchen-decoction-and-linguizhugan-decoction-ameliorate-hepatic-insulin-resistance-by-inhibiting-irs-1ser307-phosphorylation-in-vivo-and-in-vitro
#7
Huicun Zhang, Na Ta, Pengmin Chen, Hongbing Wang
Erchen decoction (ECD) and Linguizhugan decoction (LGZGD), both are Chinese herbal formula, have been used clinically for the treatment of nonalcoholic fatty liver disease (NAFLD). However, their therapeutic mechanisms are still unclear. Because insulin resistance (IR) is a key etiological factor in the pathology of high-fat diet- (HFD-) induced NAFLD, in this study, the protective effects of ECD and LGZGD on HFD-induced insulin resistance in rats were evaluated and their mechanisms were investigated by OGTT and Western blot...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28628909/nonalcoholic-fatty-liver-disease-impairs-the-cytochrome-p-450-dependent-metabolism-of-%C3%AE-tocopherol-vitamin-e
#8
Desirée Bartolini, Pierangelo Torquato, Carolina Barola, Angelo Russo, Chiara Rychlicki, Danilo Giusepponi, Guido Bellezza, Angelo Sidoni, Roberta Galarini, Gianluca Svegliati-Baroni, Francesco Galli
This study aims to investigate in in vivo and in vitro models of nonalcoholic fatty liver disease (NAFLD) the enzymatic metabolism of α-tocopherol (vitamin E) and its relationship to vitamin E-responsive genes with key role in the lipid metabolism and detoxification of the liver. The experimental models included mice fed a high-fat diet combined or not with fructose (HFD+F) and HepG2 human hepatocarcinoma cells treated with the lipogenic agents palmitate, oleate or fructose. CYP4F2 protein, a cytochrome P-450 isoform with proposed α-tocopherol ω-hydroxylase activity, decreased in HFD and even more in HFD+F mice liver; this finding was associated with increased hepatic levels of α-tocopherol and decreased formation of the corresponding long-chain metabolites α-13-hydroxy and α-13-carboxy chromanols...
June 7, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28608850/cellular-senescence-drives-age-dependent-hepatic-steatosis
#9
Mikolaj Ogrodnik, Satomi Miwa, Tamar Tchkonia, Dina Tiniakos, Caroline L Wilson, Albert Lahat, Christoper P Day, Alastair Burt, Allyson Palmer, Quentin M Anstee, Sushma Nagaraja Grellscheid, Jan H J Hoeijmakers, Sander Barnhoorn, Derek A Mann, Thomas G Bird, Wilbert P Vermeij, James L Kirkland, João F Passos, Thomas von Zglinicki, Diana Jurk
The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute to age-related tissue degeneration. Here we show that the accumulation of senescent cells promotes hepatic fat accumulation and steatosis. We report a close correlation between hepatic fat accumulation and markers of hepatocyte senescence. The elimination of senescent cells by suicide gene-meditated ablation of p16(Ink4a)-expressing senescent cells in INK-ATTAC mice or by treatment with a combination of the senolytic drugs dasatinib and quercetin (D+Q) reduces overall hepatic steatosis...
June 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28587208/xyloketal-b-attenuates-fatty-acid-induced-lipid-accumulation-via-the-srebp-1c-pathway-in-nafld-models
#10
Youying Zhang, Tian Meng, Ling Zuo, Yu Bei, Qihao Zhang, Zhijian Su, Yadong Huang, Jiyan Pang, Qi Xiang, Hongtu Yang
The goal of this study was to examine the effects of xyloketal B on nonalcoholic fatty liver disease (NAFLD) and to explore the molecular mechanisms underlying its effects in both in vivo and in vitro models. We discovered an association between xyloketal B and the sterol regulatory element-binding protein-1c (SREBP-1c) signaling pathway, which is related to lipid metabolism. Mice were dosed with xyloketal B (5, 10 and 20 mg/kg/d) and atorvastatin (15 mg/kg/d) via intraperitoneal injection once daily for 40 days after being fed a high fat diet plus 10% high fructose liquid (HFD+HFL) for 8 weeks...
June 3, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28586195/ex-vivo-cell-based-screening-platform-for-modulators-of-hepatosteatosis
#11
Shan Yu, Emily Chen, Lance Sherwood, Mitchell Hull, Ashley K Woods, Matthew S Tremblay
Nonalcoholic fatty liver disease (NAFLD) is the result of the ectopic accumulation of lipids in hepatic cells and is the early stage of liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma. While some mechanisms of aberrant lipid storage are understood, unbiased phenotypic drug screening holds the potential to identify new therapeutic small molecule mechanisms that reverse lipid accumulation in hepatic cells and prevent disease progression. Immortalized hepatocyte cell lines are often used as in vitro models of hepatocyte function, including in the study of lipid accumulation...
June 16, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28570612/caveolin1-protects-against-diet-induced-hepatic-lipid-accumulation-in-mice
#12
Meng Li, Dahua Chen, Haixiu Huang, Jiewei Wang, Xingyong Wan, Chengfu Xu, Chunxiao Li, Han Ma, Chaohui Yu, Youming Li
BACKGROUND AND AIM: Caveolin1 (CAV1) is involved in lipid homeostasis and endocytosis, but little is known about the significance of CAV1 in the pathogenesis and development of nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the role of CAV1 in NAFLD. METHODS: Expression of CAV1 in the in vitro and in vivo models of NAFLD was analyzed. The effects of CAV1 knockdown or overexpression on free fatty acid (FFA)-induced lipid accumulation in L02 cells and AML12 cells were determined...
2017: PloS One
https://www.readbyqxmd.com/read/28536464/the-protective-effect-of-human-renal-sinus-fat-on-glomerular-cells-is-reversed-by-the-hepatokine-fetuin-a
#13
R Wagner, J Machann, M Guthoff, P P Nawroth, S Nadalin, M A Saleem, N Heyne, A Königsrainer, F Fend, F Schick, A Fritsche, N Stefan, H-U Häring, E Schleicher, D I Siegel-Axel
Renal sinus fat (RSF) is a perivascular fat compartment located around renal arteries. In this in vitro and in vivo study we hypothesized that the hepatokine fetuin-A may impair renal function in non alcoholic fatty liver disease (NAFLD) by altering inflammatory signalling in RSF. To study effects of the crosstalk between fetuin-A, RSF and kidney, human renal sinus fat cells (RSFC) were isolated and cocultured with human endothelial cells (EC) or podocytes (PO). RSFC caused downregulation of proinflammatory and upregulation of regenerative factors in cocultured EC and PO, indicating a protective influence of RFSC...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28534819/ginsenoside-rb2-alleviates-hepatic-lipid-accumulation-by-restoring-autophagy-via-induction-of-sirt1-and-activation-of-ampk
#14
Qi Huang, Ting Wang, Liu Yang, He-Yao Wang
Although Panax ginseng is a famous traditional Chinese medicine and has been widely used to treat a variety of metabolic diseases including hyperglycemia, hyperlipidemia, and hepatosteatosis, the effective mediators and molecular mechanisms remain largely unknown. In this study we found that ginsenoside Rb2, one of the major ginsenosides in Panax ginseng, was able to prevent hepatic lipid accumulation through autophagy induction both in vivo and in vitro. Treatment of male db/db mice with Rb2 significantly improved glucose tolerance, decreased hepatic lipid accumulation, and restored hepatic autophagy...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28529649/sak-hv-triggered-a-short-period-lipid-lowering-biotherapy-based-on-the-energy-model-of-liver-proliferation-via-a-novel-pathway
#15
Chao Zhang, Zhiguang Huang, Haoran Jing, Wenliang Fu, Min Yuan, Wenrong Xia, Ling Cai, Xiangdong Gan, Yao Chen, Minji Zou, Minhui Long, Jiaxi Wang, Min Wang, Donggang Xu
The accumulations of excess lipids within liver and serum are defined as non-alcoholic fatty liver disease (NAFLD) and hyperlipemia respectively. Both of them are components of metabolic syndrome that greatly threaten human health. Here, a recombinant fusion protein (SAK-HV) effectively treated NAFLD and hyperlipemia in high-fat-fed ApoE(-/-) mice, quails and rats within just 14 days. Its triglyceride and cholesterol-lowering effects were significantly better than that of atorvastatin during the observation period...
2017: Theranostics
https://www.readbyqxmd.com/read/28526488/-targeting-the-gut-liver-axis-in-liver-disease
#16
REVIEW
Reiner Wiest, Agustin Albillos, Michael Trauner, Jashmohan Bajaj, Rajiv Jalan
The gut is open to the outer environment, harbours the microbiome containing several fold more genetic material than the human genome and produces a myriad of metabolites as well as hormones/peptides. The liver is at the nexus between this vast source of nutrients, toxins and hormones and the remaining human body. Not surprisingly, this liver-gut-axis has hence, been demonstrated in experimental models and in-vitro systems to contribute to the pathogenesis of most liver diseases such as alcoholic and non-alcoholic fatty liver disease (NAFLD), -steatohepatitis (NASH), cholestatic liver diseases, hepatocellular carcinoma, acute-on-chronic liver failure, progression to fibrosis/cirrhosis and complications of cirrhosis...
May 16, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28521680/fatty-acids-and-effects-on-in-vitro-and-in-vivo-models-of-liver-steatosis
#17
Laura Vergani
Fatty liver, or steatosis, is a condition of excess accumulation of lipids, mainly under form of triglycerides (TG), in the liver, and it is the hallmark of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disorder world-wide and it has frequently been associated with obesity, hyperlipidemia and insulin resistance. Free fatty acids (FA) are the major mediators of hepatic steatosis; patients with NAFLD have elevated levels of circulating FA that correlate with disease severity. Steatosis is a reversible condition that can be resolved with changed behaviors, or that can progress towards more severe liver damages such as steatohepatitis (NASH), fibrosis and cirrhosis...
May 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28507343/non-alcoholic-fatty-liver-disease-vascular-inflammation-and-insulin-resistance-are-exacerbated-by-trail-deletion-in-mice
#18
Siân P Cartland, Hanis H Harith, Scott W Genner, Lei Dang, Victoria C Cogger, Melissa Vellozzi, Belinda A Di Bartolo, Shane R Thomas, Leon A Adams, Mary M Kavurma
Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is protective of CVD. We aimed to determine whether TRAIL protects against insulin resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail (-/-) mice had increased plasma cholesterol, insulin and glucose compared to wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt, GLUT4 expression and glucose uptake in skeletal muscle...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28486193/wogonin-mitigates-nonalcoholic-fatty-liver-disease-via-enhancing-ppar%C3%AE-adipor2-in-vivo-and-in-vitro
#19
Jing Chen, Jie Liu, Ye Wang, Xuemei Hu, Feng Zhou, Yimeng Hu, Yin Yuan, Yancheng Xu
Wogonin has been reported to attenuate hyperglycemia in diabetic mice via anti-adipogenic effect on adipocytes. The potential therapeutic role of wogonin in nonalcoholic fatty liver disease (NAFLD) remains obscure. The aim of the present study was to explore the protective effect of wogonin on NAFLD mice and cultured NCTC 1469 cells exposed to palmitate. Wogonin supplementation significantly improved metabolic parameters in NAFLD mice, including body weight, blood glucose, insulin resistance, adiponectin, blood lipids, aminotransferases and hepatic histopathology...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28467181/pre-clinical-and-clinical-investigations-of-metabolic-zonation-in-liver-diseases-the-potential-of-microphysiology-systems
#20
Alejandro Soto-Gutierrez, Albert Gough, Lawrence A Vernetti, D L Taylor, Satdarshan P Monga
The establishment of metabolic zonation within a hepatic lobule ascribes specific functions to hepatocytes based on unique, location-dependent gene expression patterns. Recently, there have been significant developments in the field of metabolic liver zonation. A little over a decade ago, the role of β-catenin signaling was identified as a key regulator of gene expression and function in pericentral hepatocytes. Since then, additional molecules have been identified that regulate the pattern of Wnt/β-catenin signaling within a lobule and determine gene expression and function in other hepatic zones...
January 1, 2017: Experimental Biology and Medicine
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