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In vitro NAFLD

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https://www.readbyqxmd.com/read/29345253/3-acetyl-oleanolic-acid-ameliorates-non-alcoholic-fatty-liver-disease-in-high-fat-diet-treated-rats-by-activating-ampk-related-pathways
#1
Qiong Ou-Yang, Chun-Xiao Xuan, Xue Wang, Han-Qiong Luo, Jin-E Liu, Lan-Lan Wang, Ting-Ting Li, Yu-Peng Chen, Jun Liu
3-Acetyl-oleanolic acid (3Ac-OA) is a derivative of oleanolic acid (OA), which has shown therapeutic beneficial effects on diabetes and metabolic syndrome. In this study we investigated whether 3Ac-OA exerted beneficial effect on non-alcoholic fatty liver disease (NAFLD) in rats and its potential underlying mechanisms. Treatment with 3Ac-OA (1-100 μmol/L) dose-dependently decreased the intracellular levels of total cholesterol (TC) and triglyceride (TG) in FFA-treated primary rat hepatocytes and human HepG2 cell lines in vitro...
January 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29322544/role-of-bisphenol-a-as-environmental-factor-in-the-promotion-of-non-alcoholic-fatty-liver-disease-in%C3%A2-vitro-and-clinical-study
#2
M Dallio, M Masarone, S Errico, A G Gravina, C Nicolucci, R Di Sarno, L Gionti, C Tuccillo, M Persico, P Stiuso, N Diano, C Loguercio, A Federico
BACKGROUND: Bisphenol A is an endocrine disrupting chemical associated with type 2 diabetes mellitus (T2DM), cardiovascular disease and liver enzyme abnormalities. AIM: To evaluate bisphenol A plasma and urine levels in non-alcoholic fatty liver disease (NAFLD) patients compared to healthy subjects. Furthermore, we evaluated, in human HepG2 cells, the effects of exposure to different concentrations of bisphenol A on both oxidative stress induction and cell proliferation...
January 11, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29315766/disruption-of-adenosine-2a-receptor-exacerbates-nafld-through-increasing-inflammatory-responses-and-srebp1c-activity
#3
Yuli Cai, Honggui Li, Mengyang Liu, Ya Pei, Juan Zheng, Jing Zhou, Xianjun Luo, Wenya Huang, Linqiang Ma, Qiuhua Yang, Shaodong Guo, Xiaoqiu Xiao, Qifu Li, Tianshu Zeng, Fanyin Meng, Heather Francis, Shannon Glaser, Lulu Chen, Yuqing Huo, Gianfranco Alpini, Chaodong Wu
Adenosine 2A receptor (A2A R) exerts protective roles in endotoxin- and/or ischemia-induced tissue damages. However, the role for A2A R in non-alcoholic fatty liver disease (NAFLD) remains largely unknown. We sought to examine the effects of global and/or myeloid cell-specific A2A R disruption on the aspects of obesity-associated NAFLD and to elucidate the underlying mechanisms. Global and/or myeloid cell-specific A2A R-disrupted mice, as well as control mice were fed a high-fat diet (HFD) to induce NAFLD. Also, bone marrow-derived macrophages and primary mouse hepatocytes were examined for inflammatory and metabolic responses...
January 9, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29312569/metformin-improves-nonalcoholic-fatty-liver-disease-in-obese-mice-via-down-regulation-of-apolipoprotein-a5-as-part-of-the-ampk-lxr%C3%AE-signaling-pathway
#4
Min-Jie Lin, Wen Dai, Melanie J Scott, Rong Li, Yi-Qi Zhang, Yang Yang, Lu-Zhu Chen, Xian-Sheng Huang
Apolipoprotein A5 (apoA5) has been implicated in the formation of hepatocyte lipid droplets, a histological hallmark of non-alcoholic fatty liver disease (NAFLD). Recent evidence demonstrated that liver X receptor α (LXRα), a transcription factor involved in down-regulation of APOA5 mRNA, is activated by AMP-activated protein kinase (AMPK) that contributes to metformin-related antihyperglycemic effects. In this study we investigated the role of apoA5 and AMPK/LXRα signaling pathway in metformin-related improvement of NAFLD...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29310441/dihydromyricetin-ameliorates-nonalcoholic-fatty-liver-disease-by-improving-mitochondrial-respiratory-capacity-and-redox-homeostasis-through-modulation-of-sirt3-signaling
#5
Xianglong Zeng, Jining Yang, Ou Hu, Juan Huang, Li Ran, Mengting Chen, Yu Zhang, Xi Zhou, Jundong Zhu, Qianyong Zhang, Long Yi, Mantian Mi
AIMS: Our previous clinical trial indicated that the flavonoid dihydromyricetin (DHM) could improve hepatic steatosis in patients with NAFLD, altough the potential mechanisms of these effects remained elusive. Here, we investigated the hepatoprotective role of DHM on high-fat diet (HFD)-induced NAFLD. RESULTS: DHM supplementation could effectively ameliorate the development of NAFLD by inhibiting hepatic lipids accumulation both in HFD-fed wild type mice and in palmitic acid (PA)-induced hepatocytes...
January 8, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29299759/translating-scientific-discovery-the-need-for-preclinical-models-of-nonalcoholic-steatohepatitis
#6
REVIEW
Abdul M Oseini, Banumathi K Cole, Danny Issa, Ryan E Feaver, Arun J Sanyal
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world, affecting about 1/3 of the US general population and remaining as a significant cause of morbidity and mortality. The hallmark of the disease is the excessive accumulation of fat within the liver cells (hepatocytes), which eventually paves the way to cellular stress, injury and apoptosis. NAFLD is strongly associated with components of the metabolic syndrome and is fast emerging as a leading cause of liver transplant in the USA...
January 3, 2018: Hepatology International
https://www.readbyqxmd.com/read/29298863/dual-regulation-of-hmgb1-by-combined-jnk1-2-atf2-axis-with-mir-200-family-in-nonalcoholic-steatohepatitis-in-mice
#7
Xin Chen, Yan Ling, Yanping Wei, Jing Tang, Yibing Ren, Baohua Zhang, Feng Jiang, Hengyu Li, Ruoyu Wang, Wen Wen, Guishuai Lv, Mengchao Wu, Lei Chen, Liang Li, Hongyang Wang
In the context of diabetes, obesity, and metabolic syndrome, the inflammatory signaling has critical roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), but the underlying mechanisms remain poorly delineated. Herein, early and persistently elevated, proinflammatory cytokine HMGB1 expression was detected in a high-fat diet (HFD)-induced NAFLD model in C57BL/6 mice. The expression and extracellular release of HMGB1 was rapidly and dramatically induced by saturated palmitic acid in vitro HFD-induced inflammatory response and liver function impairment were both mitigated after the inhibition of endogenous HMGB1 by neutralizing antibody in vivo The up-regulation of HMGB1 was thought to be modified by dual channels: in the transcriptional level, it was regulated by JNK1/JNK2-ATF2 axis; post-transcriptionally, it was regulated by the microRNA (miR)-200 family, especially miR-429...
January 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295591/leonurus-japonicus-houtt-attenuates-nonalcoholic-fatty-liver-disease-in-free-fatty-acid-induced-hepg2-cells-and-mice-fed-a-high-fat-diet
#8
Mi-Ra Lee, Kwang Il Park, Jin Yeul Ma
We investigated the effects of a Leonurus japonicus ethanol extract (LJE) on nonalcoholic fatty liver disease (NAFLD). An in vitro model of hepatic steatosis was treated with 1 mM free fatty acid (FFA) in HepG2 cells. An in vivo NAFLD model was established using C57BL/6 mice fed a high-fat diet (HFD) and administered LJE (100 or 200 mg/kg) orally for 14 weeks. LJE treatment suppressed lipid accumulation and intracellular triglyceride levels significantly in a concentration-dependent manner in HepG2 cells. Moreover, LJE significantly reduced the expression of sterol regulatory element binding protein 1-c, and its downstream genes, which are associated with lipogenesis, in HepG2 cells...
December 25, 2017: Nutrients
https://www.readbyqxmd.com/read/29274380/the-nox1-isoform-of-nadph-oxidase-is-involved-in-dysfunction-of-liver-sinusoids-in-nonalcoholic-fatty-liver-disease
#9
Misaki Matsumoto, Jia Zhang, Xueqing Zhang, Junjie Liu, Joy X Jiang, Kanji Yamaguchi, Akiyuki Taruno, Masato Katsuyama, Kazumi Iwata, Masakazu Ibi, Wenhao Cui, Kuniharu Matsuno, Yoshinori Marunaka, Yoshito Itoh, Natalie J Torok, Chihiro Yabe-Nishimura
The increased production of reactive oxygen species (ROS) has been postulated to play a key role in the progression of nonalcoholic fatty liver disease (NAFLD). However, the source of ROS and mechanisms underlying the development of NAFLD have yet to be established. We observed a significant up-regulation of a minor isoform of NADPH oxidase, NOX1, in the liver of nonalcoholic steatohepatitis (NASH) patients as well as of mice fed a high-fat and high-cholesterol (HFC) diet for 8 weeks. In mice deficient in Nox1 (Nox1KO), increased levels of serum alanine aminotransferase and hepatic cleaved caspase-3 demonstrated in HFC diet-fed wild-type mice (WT) were significantly attenuated...
December 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29261513/high-content-hydrogen-water-induced-downregulation-of-mir-136-alleviates-non-alcoholic-fatty-liver-disease-by-regulating-nrf2-via-targeting-meg3
#10
Xiang Wang, Jiao Wang
This study was aimed to investigate the potential regulatory mechanism of high-content hydrogen water (HHW) in non-alcoholic fatty liver disease (NAFLD). A high-fat diet (HFD)-induced NAFLD mice model and cellular model were prepared. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TCH) and triglycerides (TG) were measured. The expression levels of representative 5 miRNAs (miR-103, miR-488, miR-136, miR-505 and miR-148a) in liver tissues were determined by quantitative real-time PCR (qRT-PCR)...
June 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29220698/synergistic-interaction-of-fatty-acids-and-oxysterols-impairs-mitochondrial-function-and-limits-liver-adaptation-during-nafld-progression
#11
Francesco Bellanti, Rosanna Villani, Rosanna Tamborra, Maria Blonda, Giuseppina Iannelli, Giorgia di Bello, Antonio Facciorusso, Giuseppe Poli, Luigi Iuliano, Carlo Avolio, Gianluigi Vendemiale, Gaetano Serviddio
The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression...
December 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/29217477/activation-of-hepatic-nogo-b-receptor-expression-a-new-anti-liver-steatosis-mechanism-of-statins
#12
Wenwen Zhang, Xiaoxiao Yang, Yuanli Chen, Wenquan Hu, Lipei Liu, Xiaomeng Zhang, Mengyang Liu, Lei Sun, Ying Liu, Miao Yu, Xiaoju Li, Luyuan Li, Yan Zhu, Qing Robert Miao, Jihong Han, Yajun Duan
Deficiency of hepatic Nogo-B receptor (NgBR) expression activates liver X receptor α (LXRα) in an adenosine monophosphate-activated protein kinase α (AMPKα)-dependent manner, thereby inducing severe hepatic lipid accumulation and hypertriglyceridemia. Statins have been demonstrated non-cholesterol lowering effects including anti-nonalcoholic fatty liver disease (NAFLD). Herein, we investigated if the anti-NAFLD function of statins depends on activation of NgBR expression. In vivo, atorvastatin protected apoE deficient or NgBR floxed, but not hepatic NgBR deficient mice, against Western diet (WD)-increased triglyceride levels in liver and serum...
December 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29190166/non-alcoholic-fatty-liver-disease-nafld-models-in-drug-discovery
#13
Banumathi K Cole, Ryan E Feaver, Brian R Wamhoff, Ajit Dash
The progressive disease spectrum of non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis (NASH), is a rapidly emerging public health crisis with no approved therapy. The diversity of various therapies under development highlights the lack of consensus around the most effective target, underscoring the need for better translatable preclinical models to study the complex progressive disease and effective therapies. Areas covered: This article reviews published literature of various mouse models of NASH used in preclinical studies, as well as complex organotypic in vitro and ex vivo liver models being developed...
December 6, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29189132/polyphenols-novel-signaling-pathways
#14
Marie-Louise Ricketts, Bradley S Ferguson
BACKGROUND: Cardiovascular disease (CVD) is currently the leading cause of death globally. The metabolic syndrome (MetS), a clustering of risk factors including hypertension, hyperglycemia, elevated low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol and increased visceral adiposity, is a significant risk factor for the development of CVD. Non-alcoholic fatty liver disease (NAFLD), often referred to as the hepatic manifestation of MetS, is a constellation of progressive liver disorders closely linked to obesity, diabetes, and insulin resistance...
November 29, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29171144/altered-fatty-acid-binding-protein-4-fabp4-expression-and-function-in-human-and-animal-models-of-hepatocellular-carcinoma
#15
Kyle J Thompson, R Garland Austin, Shayan S Nazari, Keith S Gersin, David A Iannitti, Iain H McKillop
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality. Risk factors for developing HCC include viral hepatitis, alcohol, and obesity. Fatty acid binding proteins (FABPs) bind long-chain free fatty acids (FFAs) and are expressed in a tissue-specific pattern; FABP1 being the predominant hepatic form, and FABP4 the predominant adipocyte form. The aims of this study were to investigate the expression and function of FABPs1-9 in human and animal models of obesity-related HCC...
November 24, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29167318/trail-reduces-impaired-glucose-tolerance-and-nafld-in-the-high-fat-diet-fed-mouse
#16
Stella Bernardi, Barbara Toffoli, Veronica Tisato, Fleur Bossi, Stefania Biffi, Andrea Lorenzon, Giorgio Zauli, Paola Secchiero, Bruno Fabris
AIMS/HYPOTHESIS: Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. This study aimed at evaluating whether TRAIL had the potential to treat type 2 diabetes. METHODS: Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD)...
November 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29132235/a-cell-based-assay-to-investigate-hypolipidemic-effects-of-nonalcoholic-fatty-liver-disease-therapeutics
#17
Tapan Dave, Arno William Tilles, Muralikrishna Vemula
In the recent past, there has been a growing interest in developing nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) therapeutics. As a result, a need for in vitro cell models of human hepatic steatosis and high-throughput assays to measure intracellular lipid levels has arisen. To address this growing need, we optimized the conditions based on the current literature to fatten HepG2 hepatocytes by adding a mixture of saturated and unsaturated fatty acids (oleate/palmitate, 2:1 molar ratio) without inducing any overt cytotoxicity...
November 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/29128391/preclinical-models-of-nonalcoholic-fatty-liver-disease
#18
REVIEW
Prasanna K Santhekadur, Divya P Kumar, Arun J Sanyal
Nonalcoholic fatty liver disease (NAFLD) can manifest as nonalcoholic fatty liver (NAFL) or nonalcoholic steatohepatitis (NASH). NASH is often associated with progressive fibrosis which can lead to cirrhosis and hepatocellular cancer (HCC). NASH is increasing as an etiology for end-stage liver disease as well as HCC. There are currently no approved therapies for NASH. A major barrier to development of therapeutics for NASH is the lack of preclinical models of disease that are appropriately validated to represent the biology and outcomes of human disease...
November 8, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29125642/genistein-ameliorates-fat-accumulation-through-ampk-activation-in-fatty-acid-induced-brl-cells
#19
Huijia Zhong, Huanhuan Liu, Zhuoqin Jiang
Genstein is the most abundant phytoestrogen in soybean that was reported to play positive roles in menopausal syndrome and metabolic syndrome. In the present study, we investigated the effects and potential mechanisms of genistein against progression of nonalcoholic fatty liver disease (NAFLD) in BRL cells treated with fatty acid mixture (oleate/palmitate, 2:1 ratio). Our data demonstrated that genistein remarkably improved fatty acid mixture-induced hepatocelluler fat accumulation, inhibited upregulation of genes expression related to fatty acid synthesis, and derepressed those associated with fatty acid oxidation...
November 2017: Journal of Food Science
https://www.readbyqxmd.com/read/29107687/mir-150-deficiency-ameliorated-hepatosteatosis-and-insulin-resistance-in-nonalcoholic-fatty-liver-disease-via-targeting-casp8-and-fadd-like-apoptosis-regulator
#20
Baozhong Zhuge, Guohong Li
The prevalence of Non-alcoholic fatty liver diseases (NAFLD) increased rapidly in the world. However, the pathogenesis of is still unclear. Hepatic steatosis and insulin resistance are considered to be central to the pathophysiology of NAFLD. MicroRNAs are short non-coding RNAs and has been reported to be involved in pathogenesis of NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-150 regulate hepatic steatosis and insulin resistance in high fat diet (HFD) induced NAFLD model...
October 28, 2017: Biochemical and Biophysical Research Communications
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