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In vitro NAFLD

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https://www.readbyqxmd.com/read/28526488/-targeting-the-gut-liver-axis-in-liver-disease
#1
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
#2
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
#3
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
#4
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...
May 6, 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
#5
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
https://www.readbyqxmd.com/read/28456640/adrenic-acid-as-an-inflammation-enhancer-in-non-alcoholic-fatty-liver-disease
#6
Saut Nababan, Shin Nishiumi, Yuki Kawano, Takashi Kobayashi, Masaru Yoshida, Takeshi Azuma
BACKGROUND: This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). METHODS: We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed...
April 26, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28429344/up-regulation-of-microrna-367-promotes-liver-steatosis-through-repressing-tbl1-in-obese-mice
#7
D-D Li, Y Liu, L Xue, D-Y Su, W-Y Pang
OBJECTIVE: Increasing evidence has demonstrated that microRNAs (miRNAs) play a critical role in the progression of metabolic disorders, including obesity-induced non-alcoholic fatty liver disease (NAFLD). In the present study, the expression and function of miR-367 were investigated. MATERIALS AND METHODS: C57BL/6 male mice aged 8 weeks were fed with a normal diet (ND) or high-fat-diet (HFD). The expression levels of miR-367 were analyzed in livers from two groups of mice by quantitative real-time PCR...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28420164/the-angiogenesis-inhibitor-als-l1023-from-lemon-balm-leaves-attenuates-high-fat-diet-induced-nonalcoholic-fatty-liver-disease-through-regulating-the-visceral-adipose-tissue-function
#8
Jeongjun Kim, Haerim Lee, Jonghoon Lim, Jaeho Oh, Soon Shik Shin, Michung Yoon
Similar to neoplastic tissues, growth and development of adipose tissue are thought to be angiogenesis-dependent. Since visceral adipose tissue (VAT) is associated with development and progression of nonalcoholic fatty liver disease (NAFLD), we hypothesized that angiogenesis inhibition would attenuate obesity-induced NAFLD. We fed C57BL/6J mice a low-fat diet (LFD, chow 10% kcal fat), a high-fat diet (HFD, 45% kcal fat) or HFD supplemented with the lemon-balm extract ALS-L1023 (HFD-ALS) for 15 weeks. ALS-L1023 reduced endothelial cell-tube formation in vitro...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28368295/homocysteine-induces-hepatic-steatosis-involving-er-stress-response-in-high-methionine-diet-fed-mice
#9
Yanbiao Ai, Zhenzhen Sun, Chuan Peng, Lingli Liu, Xiaoqiu Xiao, Jibin Li
Elevated circulating homocysteine (Hcy) has been proposed to be associated with non-alcoholic fatty liver disease (NAFLD). It is also reported that Hcy causes protein misfolding in the endoplasmic reticulum (ER). In this study, we used a high methionine diet (HMD)-fed mouse model and cultured primary hepatocytes to investigate the effects of Hcy on hepatic lipids metabolism. C57BL/6J mice received either standard chow diet (CT, n = 10) or diet supplemented with 2% methionine (MET, n = 10) for 16 weeks. In in vitro experiments, cultured mouse primary hepatocytes were treated with Hcy, or Hcy combined with 4-phenylbutyric acid (4-PBA), or tunicamycin (TM), respectively...
April 1, 2017: Nutrients
https://www.readbyqxmd.com/read/28351695/antihyperlipidemic-and-hepatoprotective-effects-of-gardenin-a-in-cellular-and-high-fat-diet-fed-rodent-models
#10
Erenius Toppo, S Sylvester Darvin, S Esakkimuthu, A Stalin, K Balakrishna, K Sivasankaran, P Pandikumar, S Ignacimuthu, N A Al-Dhabi
The gum of Gardenia resinifera Roth., is one of the important drugs used in the Indian system of medicine and a source of unique polymethoxylated flavones. This study was aimed to evaluate the antihyperlipidemic and anti-NAFLD effects of Gardenin A (Gar-A) from G. resinifera gum using in vitro and in vivo models. Gar-A was isolated from G. resinifera gum and was identified on the basis of the physical and spectral data. Toxicity of Gar-A to HepG2 cells was evaluated using MTT assay. The ability of Gar-A to reduce steatosis was assessed using oleate-palmitate induced HepG2 cell lines by estimating the lipid levels by ORO staining and by estimating the intracellular triglyceride content...
May 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28347804/o-glcnac-transferase-promotes-fatty-liver-associated-liver-cancer-through-inducing-palmitic-acid-and-activating-endoplasmic-reticulum-stress
#11
Weiqi Xu, Xiang Zhang, Jian-Lin Wu, Li Fu, Ken Liu, Dabin Liu, George Gong Chen, Paul Bo-San Lai, Nathalie Wong, Jun Yu
BACKGROUND & AIMS: O-GlcNAc transferase (OGT) is a unique glycosyltransferase involved in metabolic reprogramming. We investigated the functional role of OGT in non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). METHODS: The biological function of OGT in NAFLD-HCC was determined by gain- or loss- of OGT functional assays in vitro and in nude mice. OGT target factors and pathways were identified by liquid chromatography-tandem mass spectrometry (LC-MS), promoter luciferase assay, DNA binding activity assay and Western blot...
March 25, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28303724/non-alcoholic-fatty-liver-disease-nafld-pathogenesis-classification-and-effect-on-drug-metabolizing-enzymes-and-transporters
#12
Enoch Cobbina, Fatemeh Akhlaghi
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5% of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a "three-hit" process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 has been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD...
March 17, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28300213/effect-of-modulation-of-ppar-%C3%AE-activity-on-kupffer-cells-m1-m2-polarization-in-the-development-of-non-alcoholic-fatty-liver-disease
#13
Wenjing Luo, Qinyu Xu, Qi Wang, Huimin Wu, Jing Hua
Abnormal lipid-mediated hepatic inflammatory-immune dysfunction and chronic low grade inflammation play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Macrophage polarization is an important mechanism for the regulation of inflammatory response. Since PPAR-γ has emerged as a master regulator of macrophage polarization, we aimed to investigate the lipid-induced macrophage/Kupffer cell polarization in vivo and in vitro, and explore the association between PPAR-γ activity and macrophages M1/M2 polarization shifting...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28264657/-non-alcoholic-fatty-liver-disease-and-enos-dysfunction-in-humans
#14
Marcello Persico, Mario Masarone, Antonio Damato, Mariateresa Ambrosio, Alessandro Federico, Valerio Rosato, Tommaso Bucci, Albino Carrizzo, Carmine Vecchione
BACKGROUND: NAFLD is associated to Insulin Resistance (IR). IR is responsible for Endothelial Dysfunction (ED) through the impairment of eNOS function. Although eNOS derangement has been demonstrated in experimental models, no studies have directly shown that eNOS dysfunction is associated with NAFLD in humans. The aim of this study is to investigate eNOS function in NAFLD patients. METHODS: Fifty-four NAFLD patients were consecutively enrolled. All patients underwent clinical and laboratory evaluation and liver biopsy...
March 7, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28251449/a20-attenuates-liver-fibrosis-in-nafld-and-inhibits-inflammation-responses
#15
Xiaohan Wang, Luoyan Ai, Qingqing Xu, Changwei Wu, Zhiwei Chen, Dazhi Su, Xiaoke Jiang, Zhuping Fan
We previously reported A20 was able to inhibit lipid accumulation in nonalcoholic steatohepatitis. We want to investigate whether A20 influences liver fibrosis in this study. Liver tissues from patients with hepatic fibrosis (n = 9) and healthy individuals (n = 7) were studied for A20 protein level by immunohistochemistry. A20 messenger RNA (mRNA) and protein level were also analyzed in two murine hepatic fibrosis models: methionine- and choline-deficient (MCD) diet and extrahepatic bile duct ligation (BDL) operation by real-time PCR and western blot...
March 1, 2017: Inflammation
https://www.readbyqxmd.com/read/28235613/impaired-hepatic-lipid-synthesis-from-polyunsaturated-fatty-acids-in-tm6sf2-e167k-variant-carriers-with-nafld
#16
Panu K Luukkonen, You Zhou, P A Nidhina Haridas, Om P Dwivedi, Tuulia Hyötyläinen, Ashfaq Ali, Anne Juuti, Marja Leivonen, Taru Tukiainen, Linda Ahonen, Emma Scott, Jeremy M Palmer, Johanna Arola, Marju Orho-Melander, Petter Vikman, Quentin M Anstee, Vesa M Olkkonen, Matej Orešič, Leif Groop, Hannele Yki-Järvinen
BACKGROUND: Carriers of the transmembrane 6 superfamily member 2 E167K gene variant (TM6SF2(EK/KK)) have decreased expression of the TM6SF2 gene and increased risk of NAFLD and NASH. Unlike common 'obese/metabolic' NAFLD, these subjects lack hypertriglyceridemia and have lower risk of cardiovascular disease. In animals, phosphatidylcholine (PC) deficiency results in a similar phenotype. PCs surround the core of VLDL consisting of triglycerides (TGs) and cholesteryl-esters (CEs). We determined the effect of the TM6SF2 E167K on these lipids in the human liver and serum and on hepatic gene expression and studied the effect of TM6SF2 knockdown on hepatocyte handling of these lipids...
February 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28194019/il-25-stimulates-m2-macrophage-polarization-and-thereby-promotes-mitochondrial-respiratory-capacity-and-lipolysis-in-adipose-tissues-against-obesity
#17
Juan Feng, Lingyi Li, Zhiying Ou, Qiao Li, Baoyong Gong, Zhenxian Zhao, Weiwei Qi, Ti Zhou, Jun Zhong, Weibin Cai, Xia Yang, Aiping Zhao, Guoquan Gao, Zhonghan Yang
Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells, especially macrophages. Immune molecules, including some cytokines, have a close relationship with metabolism. Interleukin (IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction; however, its role and mechanisms in lipid metabolism remain to be extensively clarified. Human serum and liver biopsy specimens, high-fat diet-induced obesity mice and DB/DB (Lepr-/-) animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases (NAFLD)...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28167322/nlrp3-inflammasome-blockade-reduces-liver-inflammation-and-fibrosis-in-experimental-nash-in-mice
#18
Auvro R Mridha, Alexander Wree, Avril A B Robertson, Matthew M Yeh, Casey D Johnson, Derrick M Van Rooyen, Fahrettin Haczeyni, Narci C-H Teoh, Christopher Savard, George N Ioannou, Seth L Masters, Kate Schroder, Matthew A Cooper, Ariel E Feldstein, Geoffrey C Farrell
BACKGROUND & AIMS: NOD-like receptor protein 3 (NLRP3) inflammasome activation occurs in Non-alcoholic fatty liver disease (NAFLD). We used the first small molecule NLRP3 inhibitor, MCC950, to test whether inflammasome blockade alters inflammatory recruitment and liver fibrosis in two murine models of steatohepatitis. METHODS: We fed foz/foz and wild-type mice an atherogenic diet for 16weeks, gavaged MCC950 or vehicle until 24weeks, then determined NAFLD phenotype...
May 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28153708/steroidogenic-acute-regulatory-protein-star-overexpression-attenuates-hfd-induced-hepatic-steatosis-and-insulin-resistance
#19
Yanyan Qiu, Xianxian Sui, Yongkun Zhan, Chen Xu, Xiaobo Li, Yanxia Ning, Xiuling Zhi, Lianhua Yin
Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology. Intracellular lipid accumulation is the first step in the development and progression of NAFLD. Steroidogenic acute regulatory protein (StAR) plays an important role in the synthesis of bile acid and intracellular lipid homeostasis and cholesterol metabolism. We hypothesize that StAR is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. The hypothesis was identified using free fatty acid (FFA)-overloaded NAFLD in vitro model and high-fat diet (HFD)-induced NAFLD mouse model transfected by recombinant adenovirus encoding StAR (StAR)...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28146130/effects-of-natural-products-on-fructose-induced-nonalcoholic-fatty-liver-disease-nafld
#20
REVIEW
Qian Chen, Tingting Wang, Jian Li, Sijian Wang, Feng Qiu, Haiyang Yu, Yi Zhang, Tao Wang
As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance...
January 31, 2017: Nutrients
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