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In vitro NAFLD

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https://www.readbyqxmd.com/read/28303724/non-alcoholic-fatty-liver-disease-nafld-pathogenesis-classification-and-effect-on-drug-metabolizing-enzymes-and-transporters
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
February 3, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28153708/steroidogenic-acute-regulatory-protein-star-overexpression-attenuates-hfd-induced-hepatic-steatosis-and-insulin-resistance
#8
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
#9
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
https://www.readbyqxmd.com/read/28128372/the-hepatoprotective-effect-of-phyllanthus-emblica-l-fruit-on-high-fat-diet-induced-non-alcoholic-fatty-liver-disease-nafld-in-sd-rats
#10
Cheng-Ze Huang, Yu-Tang Tung, Shih-Min Hsia, Chi-Hao Wu, Gow-Chin Yen
Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is closely associated with metabolic syndrome and refers to the accumulation of hepatic steatosis not due to excess alcohol consumption. Phyllanthus emblica L. is a rich source of gallic acid and many known medicinally phytochemicals such as tannins, lignans, flavonoids, alkaloids, vitamin C, mucic acid, and ellagic acid. Our previous study has revealed that P. emblica exhibits inhibitory effects on hepatic steatosis and liver fibrosis in vitro, as well as gallic acid improves high fat diet (HFD)-induced dyslipidaemia, hepatosteatosis, and oxidative stress in vivo...
February 22, 2017: Food & Function
https://www.readbyqxmd.com/read/28127194/three-dimensional-perfused-human-in-vitro-model-of-non-alcoholic-fatty-liver-disease
#11
Tomasz Kostrzewski, Terri Cornforth, Sophie A Snow, Larissa Ouro-Gnao, Cliff Rowe, Emma M Large, David J Hughes
AIM: To develop a human in vitro model of non-alcoholic fatty liver disease (NAFLD), utilising primary hepatocytes cultured in a three-dimensional (3D) perfused platform. METHODS: Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids (FFA) from culture medium was monitored...
January 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28123944/celastrol-ameliorates-liver-metabolic-damage-caused-by-a-high-fat-diet-through-sirt1
#12
Yinliang Zhang, Chao Geng, Xiaoyan Liu, Meixia Li, Mingyue Gao, Xiaojun Liu, Fude Fang, Yongsheng Chang
OBJECTIVE: Celastrol was recently identified as a potential novel treatment for obesity. However, the effect of Celastrol on nonalcoholic fatty liver disease (NAFLD) remains elusive. The aim of this study is to evaluate the role of Celastrol in NAFLD. METHODS: Functional studies were performed using wild-type C57BL/6J (WT) mice and liver specific Sirt1-deficient (LKO) mice. The molecular mechanism was explored in primary mouse liver and primary hepatocytes. RESULTS: When WT mice receiving a high-fat diet (HFD) were treated with Celastrol, reductions in body weight, subcutaneous and visceral fat content, and liver lipid droplet formation were observed, along with reduced hepatic intracellular triglyceride and serum triglyceride, free fatty acid, and ALT concentrations...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28119530/decreased-lipid-metabolism-but-increased-fa-biosynthesis-are-coupled-with-changes-in-liver-micrornas-in-obese-subjects-with-nafld
#13
J Latorre, J M Moreno-Navarrete, J M Mercader, M Sabater, Ò Rovira, J Gironès, W Ricart, J M Fernández-Real, F J Ortega
BACKGROUND/OBJECTIVE: Many controversies regarding the association of liver miRNAs with obesity and nonalcoholic fatty liver diseases (NAFLD) call for additional validations. This study sought to investigate variations in genes and hepatic miRNAs in a sample of obese patients with or without NAFLD and human hepatocytes. SUBJECTS/METHODS: Sixty non-consecutive obese women following bariatric surgery were recruited. Subjects were classified as NAFLD (n=17), borderline (n=24), and controls (n=19) with normal enzymatic profile, liver histology, and ultrasound assessments...
January 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28110314/long-term-exposure-to-a-butter-rich-diet-induces-mild-to-moderate-steatosis-in-chang-liver-cells-and-swiss-albino-mice-models
#14
Thomas John Philip Nalloor, Nitesh Kumar, Kasinathan Narayanan, Vasanth Raj Palanimuthu
BACKGROUND: Butter is one of the widely used fats present in the diet. However, there is no satisfactory study available that evaluates the effect of a high-fat diet containing butter as the principal fat on the development of non-alcoholic fatty liver disease (NAFLD). METHODS: In the present study, butter was used for the development of steatosis in Chang liver cells in an in vitro study and Swiss albino mice in an in vivo study. In vitro steatosis was established, and butter was compared with oleic acid in Chang liver cells using an oil red O (ORO)-based colorimetric assay...
January 23, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28106137/ameliorative-effects-of-compound-k-and-ginsenoside-rh1-on-non-alcoholic-fatty-liver-disease-in-rats
#15
Xu-Jia Chen, Wen-Jing Liu, Meng-Liang Wen, Hong Liang, Shao-Mei Wu, Yun-Zhen Zhu, Jiang-Yuan Zhao, Xiang-Qian Dong, Ming-Gang Li, Li Bian, Cheng-Gang Zou, Lan-Qing Ma
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease, which has no standard treatment available. Panax notoginseng saponines (PNS) have recently been reported to protect liver against hepatocyte injury induced by ethanol or high fat diet (HFD) in rats. Compound K and ginsenoside Rh1 are the main metabolites of PNS. In this study, we evaluated the effects of CK and Rh1 on NAFLD. Rats fed HFD showed significant elevations in liver function markers, lipids, glucose tolerance, and insulin resistance...
January 20, 2017: Scientific Reports
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
#16
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
#17
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
#18
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
#19
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
#20
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
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