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In vitro NAFLD

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https://www.readbyqxmd.com/read/29132235/a-cell-based-assay-to-investigate-hypolipidemic-effects-of-nonalcoholic-fatty-liver-disease-therapeutics
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/29106426/effect-of-a-novel-potential-probiotic-lactobacillus-paracasei-jlus66-isolated-from-fermented-milk-on-nonalcoholic-fatty-liver-in-rats
#5
Haiqing Ye, Qian Li, Zhengzhe Zhang, Maocheng Sun, Changhui Zhao, Tiehua Zhang
Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease worldwide. Previous evidence indicates that probiotics can be applied as a therapeutic agent for NAFLD. In this study, the potential probiotic strain Lactobacillus paracasei Jlus66 was isolated from natural fermented milk by a culture-dependent method, and its probiotic potentials were tested by established in vitro tests. In addition, the protective effect of Lactobacillus paracasei Jlus66 against NAFLD was evaluated in rat models...
November 6, 2017: Food & Function
https://www.readbyqxmd.com/read/29090980/dolichos-lablab-protects-against-nonalcoholic-fatty-liver-disease-in-mice-fed-high-fat-diets
#6
A-Rang Im, Yun Hee Kim, Young Hwa Kim, Won-Kyung Yang, Seung Hyung Kim, Kwang Hoon Song
Hyacinth bean, Dolichos lablab or Lablab purpureus, has been used for centuries in India and China as an edible pod and animal forage, as well as to treat diarrhea and other gastrointestinal disease in traditional Korean medicine. Recently, we have demonstrated that D. lablab extract (DLL-Ex) prevented free fatty acid-induced lipid accumulation in an in vitro cellular nonalcoholic fatty liver disease (NAFLD) model. In this study, we, thus, aimed at clarifying the hepatoprotective effects of DLL-Ex in a high-fat diet-induced in vivo animal NAFLD model, as well as at elucidating underlying mechanisms of identified effects...
November 1, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29031724/elevated-hepatic-dpp4-activity-promotes-insulin-resistance-and-non-alcoholic-fatty-liver-disease
#7
Christian Baumeier, Luisa Schlüter, Sophie Saussenthaler, Thomas Laeger, Maria Rödiger, Stella Amelie Alaze, Louise Fritsche, Hans-Ulrich Häring, Norbert Stefan, Andreas Fritsche, Robert Wolfgang Schwenk, Annette Schürmann
OBJECTIVE: Increased hepatic expression of dipeptidyl peptidase 4 (DPP4) is associated with non-alcoholic fatty liver disease (NAFLD). Whether this is causative for the development of NAFLD is not yet clarified. Here we investigate the effect of hepatic DPP4 overexpression on the development of liver steatosis in a mouse model of diet-induced obesity. METHODS: Plasma DPP4 activity of subjects with or without NAFLD was analyzed. Wild-type (WT) and liver-specific Dpp4 transgenic mice (Dpp4-Liv-Tg) were fed a high-fat diet and characterized for body weight, body composition, hepatic fat content and insulin sensitivity...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28989978/the-therapeutic-potential-of-resveratrol-a-review-of-clinical-trials
#8
Adi Y Berman, Rachel A Motechin, Maia Y Wiesenfeld, Marina K Holz
Resveratrol is a nutraceutical with several therapeutic effects. It has been shown to mimic effects of caloric restriction, exert anti-inflammatory and anti-oxidative effects, and affect the initiation and progression of many diseases through several mechanisms. While there is a wealth of in vitro and in vivo evidence that resveratrol could be a promising therapeutic agent, clinical trials must confirm its potential. In this work, we reviewed the current clinical data available regarding the pharmacological action of resveratrol...
2017: NPJ Precis Oncol
https://www.readbyqxmd.com/read/28987868/impairment-of-akt-activity-by-cyp2e1-mediated-oxidative-stress-is-involved-in-chronic-ethanol-induced-fatty-liver
#9
Tao Zeng, Cui-Li Zhang, Ning Zhao, Min-Jie Guan, Mo Xiao, Rui Yang, Xiu-Lan Zhao, Li-Hua Yu, Zhen-Ping Zhu, Ke-Qin Xie
Protein kinase B (PKB/Akt) plays important roles in the regulation of lipid homeostasis, and impairment of Akt activity has been demonstrated to be involved in the development of non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that cytochrome P4502E1 (CYP2E1) plays causal roles in the pathogenesis of alcoholic fatty liver (AFL). We hypothesized that Akt activity might be impaired due to CYP2E1-induced oxidative stress in chronic ethanol-induced hepatic steatosis. In this study, we found that chronic ethanol-induced hepatic steatosis was accompanied with reduced phosphorylation of Akt at Thr308 in mice liver...
September 27, 2017: Redox Biology
https://www.readbyqxmd.com/read/28971098/the-nutraceutic-silybin-counteracts-excess-lipid-accumulation-and-ongoing-oxidative-stress-in-an-in-vitro-model-of-non-alcoholic-fatty-liver-disease-progression
#10
Giulia Vecchione, Elena Grasselli, Federica Cioffi, Francesca Baldini, Paulo J Oliveira, Vilma A Sardão, Katia Cortese, Antonia Lanni, Adriana Voci, Piero Portincasa, Laura Vergani
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and mortality. Oxidative stress and release of pro-inflammatory cytokines, such as tumor necrosis factor α (TNFα), are major consequences of hepatic lipid overload, which can contribute to progression of NAFLD to non-alcoholic steatohepatitis (NASH). Also, mitochondria are involved in the NAFLD pathogenesis for their role in hepatic lipid metabolism. Definitive treatments for NAFLD/NASH are lacking so far. Silybin, the extract of the milk thistle seeds, has previously shown beneficial effects in NAFLD...
2017: Frontiers in Nutrition
https://www.readbyqxmd.com/read/28965028/angiopoietin-like-protein-8-an-attractive-biomarker-for-the-evaluation-of-subjects-with-insulin-resistance-and-related-disorders
#11
REVIEW
Su Wang, Xiafei Hong, Zhigang Tu, Guoyue Yuan
Insulin resistance is prevalent worldwide and is associated with many metabolic diseases, in particular, type 2 diabetes mellitus (T2DM), obesity, nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS) and metabolic syndrome (MetS). Angiopoietin-like protein 8 (ANGPTL8), a newly-identified secreted protein composing of 198 amino acids, is enriched in the liver of human. Considering its promising potential for β-cell proliferation and therapeutic prospect for diabetes, ANGPTL8 has aroused extensive interests...
November 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28951211/microrna-194-inhibition-improves-dietary-induced-non-alcoholic-fatty-liver-disease-in-mice-through-targeting-on-fxr
#12
Hezhongrong Nie, Chunli Song, Daming Wang, Shengjin Cui, Tingyu Ren, Zhaopeng Cao, Qing Liu, Zeyan Chen, Xiaoyong Chen, Yiwen Zhou
Non-alcoholic fatty liver disease (NAFLD) affects obesity-associated metabolic syndrome, which exhibits hepatic steatosis, insulin insensitivity and glucose intolerance. Previous studies indicated that hepatic microRNAs (miRs) play critical roles in the development of NAFLD. In this study, we aim to explore the pathophysiological role of miR-194 in obesity-mediated metabolic dysfunction. Our findings show that the high fat diet or palmitic acid treatment significantly increase hepatic miR-194 levels in vivo and in vitro...
September 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28950858/identification-of-deleterious-rare-variants-in-mttp-pnpla3-and-tm6sf2-in-japanese-males-and-association-studies-with-nafld
#13
Supichaya Boonvisut, Ken Yoshida, Kazuhiro Nakayama, Kazuhisa Watanabe, Hiroshi Miyashita, Sadahiko Iwamoto
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by excessive fat deposits in hepatocytes without excessive alcohol intake. NAFLD is influenced by genetic factors, and the heritability has been estimated at 0.35 to 0.6 by twin studies. We explored rare variants in known NAFLD-associated genes to investigate whether these rare variants are involved in the susceptibility to NAFLD. METHODS: The target genes for re-sequencing were PNPLA3, TM6SF2, and MTTP...
September 26, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28946547/pioglitazone-suppresses-inflammation-and-fibrosis-in-nonalcoholic-fatty-liver-disease-by-down-regulating-pdgf-and-timp-2-evidence-from-in-vitro-study
#14
Wen Deng, Zimin Meng, Aitao Sun, Yan Wang, Zhihong Yang
BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide. Pioglitazone is a pharmacologic agonist of peroxisome proliferators-activated receptor-γ (PPAR-γ) that was reported to ameliorate hepatic steatosis and inflammatory changes. OBJECTIVE: We aimed to evaluate the effects of pioglitazone in NAFLD and investigate the underlying mechanism by testing platelet derived growth factor (PDGF) and tissue inhibitory of metalloproteinase-2 (TIMP-2)...
September 1, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28931917/exercise-training-enhances-in-vivo-clearance-of-endotoxin-and-attenuates-inflammatory-responses-by-potentiating-kupffer-cell-phagocytosis
#15
Shoichi Komine, Kentaro Akiyama, Eiji Warabi, Sechang Oh, Keisuke Kuga, Kazunori Ishige, Shinji Togashi, Toru Yanagawa, Junichi Shoda
The failure of Kupffer cells (KCs) to remove endotoxin is an important factor in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In this study, the effects of exercise training on KC function were studied in terms of in vivo endotoxin clearance and inflammatory responses. Mice were allocated into rest and exercise groups. KC bead phagocytic capacity and plasma steroid hormone levels were determined following exercise training. Endotoxin and inflammatory cytokine levels in plasma were determined over time following endotoxin injection...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924233/pharmacological-inhibition-of-camkk2-with-the-selective-antagonist-sto-609-regresses-nafld
#16
Brian York, Feng Li, Fumin Lin, Kathrina L Marcelo, Jianqiang Mao, Adam Dean, Naomi Gonzales, David Gooden, Suman Maity, Cristian Coarfa, Nagireddy Putluri, Anthony R Means
Binding of calcium to its intracellular receptor calmodulin (CaM) activates a family of Ca(2+)/CaM-dependent protein kinases. CaMKK2 (Ca(2+)/CaM-dependent protein kinase kinase 2) is a central member of this kinase family as it controls the actions of a CaMK cascade involving CaMKI, CaMKIV or AMPK. CaMKK2 controls insulin signaling, metabolic homeostasis, inflammation and cancer cell growth highlighting its potential as a therapeutic target for a variety of diseases. STO-609 is a selective, small molecule inhibitor of CaMKK2...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28905319/pi3k-inhibition-protects-mice-from-nafld-by-down-regulating-cmklr1-and-nlrp3-in-kupffer-cells
#17
Wenfeng Zhang, Yan Liu, Mingbing Wu, Xiwen Zhu, Tao Wang, Kun He, Peizhi Li, Xiaoling Wu
Inflammation induced by high-fat diet (HFD) is of critical importance in the development of hepatic steatosis. The role of chemerin in the progress of nonalcoholic fatty liver disease (NAFLD) remains controversial. Here, we have evaluated the effects and mechanism of chemerin on insulin sensitivity and inflammation. An inhibitor (wortmannin) and agonist (insulin-like growth factor 1 (IGF-1) of phosphatidyl inositol 3-kinase (PI3K) were applied to Kupffer cells (KCs) after treatment with a concentration gradient of chemerin in vitro...
November 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28899784/mir-181b-regulates-steatosis-in-nonalcoholic-fatty-liver-disease-via-targeting-sirt1
#18
Yunxia Wang, Kongxi Zhu, Weihua Yu, Hongjuan Wang, Lan Liu, Qiong Wu, Shuai Li, Jianqiang Guo
Non-alcoholic fatty liver diseases (NAFLD) is one of the leading cause of chronic liver diseases in the world. However, the pathogenesis of NAFLD is still unclear. Emerging studies have demonstrated that microRNAs (miRs) are profoundly involved in NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-181b influences NAFLD via direct targeting SIRT1. The expression of miR181b was up-regulated while SIRT1 was down-regulated in both human NAFLD patients and high fat diet (HFD) induced NAFDL mice model...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28895929/effects-of-oral-administration-of-silymarin-in-a-juvenile-murine-model-of-non-alcoholic-steatohepatitis
#19
Veronica Marin, Silvia Gazzin, Sabrina E Gambaro, Matteo Dal Ben, Sonia Calligaris, Monica Anese, Alan Raseni, Claudio Avellini, Pablo J Giraudi, Claudio Tiribelli, Natalia Rosso
The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents is challenging the global care system. No therapeutic strategies have been defined so far, and changes in the lifestyle remain the only alternative. In this study, we assessed the protective effects of silymarin in a juvenile non-alcoholic steatohepatitis (NASH) model and the in vitro effects on fat-laden human hepatocytes. C57Bl/6 mice were exposed to HFHC diet immediately after weaning. After eight weeks, animals showed histological signs of NASH...
September 12, 2017: Nutrients
https://www.readbyqxmd.com/read/28877979/fatty-acids-promote-fatty-liver-disease-via-the-dysregulation-of-3-mercaptopyruvate-sulfurtransferase-hydrogen-sulfide-pathway
#20
Meng Li, Chengfu Xu, Junping Shi, Jiexia Ding, Xingyong Wan, Dahua Chen, Jianguo Gao, Chunxiao Li, Jie Zhang, Yiming Lin, Zhenhua Tu, Xiaoni Kong, Youming Li, Chaohui Yu
OBJECTIVE: Accumulation of free fatty acids (FFAs) in hepatocytes induces lipotoxicity, leading to non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the underlying mechanisms by which FFA contributes to the pathogenesis of NAFLD via the regulation of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous hydrogen sulfide (H2S) biosynthesis. DESIGN: Hepatic MPST expression was evaluated in mice and patients with NAFLD...
September 6, 2017: Gut
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