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Non-alcoholic steatosis

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https://www.readbyqxmd.com/read/28212548/branched-chain-amino-acids-prevent-hepatic-fibrosis-and-development-of-hepatocellular-carcinoma-in-a-non-alcoholic-steatohepatitis-mouse-model
#1
Kai Takegoshi, Masao Honda, Hikari Okada, Riuta Takabatake, Naoto Matsuzawa-Nagata, Jean S Campbell, Masashi Nishikawa, Tetsuro Shimakami, Takayoshi Shirasaki, Yoshio Sakai, Taro Yamashita, Toshinari Takamura, Takuji Tanaka, Shuichi Kaneko
Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211103/impaired-learning-and-memory-in-rats-induced-by-a-high-fat-diet-involvement-with-the-imbalance-of-nesfatin-1-abundance-and-copine-6-expression
#2
Zheng Chen, Ya-Yun Xu, Rui Wu, Yin-Xiu Han, Yue Yu, Jin-Fang Ge, Fei-Hu Chen
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, resulting not only in liver dysfunction, glucose and lipid metabolism disorder, but also in neuropsychiatric damage. In the present study, a NAFLD rat model was established via feeding of a high-fat diet, and the behavior was observed via the open field test (OFT), the sucrose preference test (SPT), the elevated plus maze (EPM), the forced swimming test (FST), and the Morris water maze (MWM). The plasma concentrations of alanine aminotransferase (ALT), glucose, free fatty acid (FFA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were detected using chemiluminescence technique...
February 17, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28205519/mitochondrial-atp-transporter-depletion-protects-mice-against-liver-steatosis-and-insulin-resistance
#3
Joonseok Cho, Yujian Zhang, Shi-Young Park, Anna-Maria Joseph, Chul Han, Hyo-Jin Park, Srilaxmi Kalavalapalli, Sung-Kook Chun, Drake Morgan, Jae-Sung Kim, Shinichi Someya, Clayton E Mathews, Young Jae Lee, Stephanie E Wohlgemuth, Nishanth E Sunny, Hui-Young Lee, Cheol Soo Choi, Takayuki Shiratsuchi, S Paul Oh, Naohiro Terada
Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in obese individuals. Adenine nucleotide translocase (ANT) exchanges ADP/ATP through the mitochondrial inner membrane, and Ant2 is the predominant isoform expressed in the liver. Here we demonstrate that targeted disruption of Ant2 in mouse liver enhances uncoupled respiration without damaging mitochondrial integrity and liver functions. Interestingly, liver specific Ant2 knockout mice are leaner and resistant to hepatic steatosis, obesity and insulin resistance under a lipogenic diet...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28202906/bar502-a-dual-fxr-and-gpbar1-agonist-promotes-browning-of-white-adipose-tissue-and-reverses-liver-steatosis-and-fibrosis
#4
Adriana Carino, Sabrina Cipriani, Silvia Marchianò, Michele Biagioli, Chiara Santorelli, Annibale Donini, Angela Zampella, Maria Chiara Monti, Stefano Fiorucci
Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease. Here, we have investigated whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose. After 9 week, mice on HFD gained ≈30% of b.w (P < 0.01 versus naïve) and were insulin resistant. These overweighting and insulin resistant mice were randomized to receive HFD or HFD in combination with BAR502. After 18 weeks, HFD mice developed NASH like features with severe steato-hepatitis and fibrosis, increased hepatic content of triacylglycerol and cholesterol and expression of SREPB1c, FAS, ApoC2, PPARα and γ, α-SMA, α1 collagen and MCP1 mRNAs...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28190475/calycosin-attenuates-triglyceride-accumulation-and-hepatic-fibrosis-in-murine-model-of-non-alcoholic-steatohepatitis-via-activating-farnesoid-x-receptor
#5
Xingping Duan, Qiang Meng, Changyuan Wang, Zhihao Liu, Qi Liu, Huijun Sun, Pengyuan Sun, Xiaobo Yang, Xiaokui Huo, Jinyong Peng, Kexin Liu
BACKGROUND: Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury. PURPOSE: The present study was to investigate the hepatoprotective effect of calycosin on attenuating triglyceride accumulation and hepatic fibrosis, as well as explore the potential mechanism in murine model of NASH...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28184028/long-term-administration-of-tacrolimus-and-everolimus-prevents-high-cholesterol-high-fructose-induced-steatosis-in-c57bl-6j-mice-by-inhibiting-de-novo-lipogenesis
#6
Sharma Love, Malik A Mudasir, Subhash C Bhardwaj, Gurdarshan Singh, Sheikh A Tasduq
AIM: To investigate the effects of tacrolimus (TC) and everolimus (EV) on non-alcoholic steatohepatitis (NASH) induced by high fat, high cholesterol and fructose (fast food) diet in C57BL/6J mice. MATERIALS AND METHODS: C57BL/6J mice were divided into four groups (n=8). 1) Standard Chow (SC); 2) Fast food (FF) diet; 3) FF + Tacrolimus (TC, 1mg/kg) and; 4) FF + Everolimus (EV, 1mg/kg) and treated for 16 weeks. Serum and tissue samples were analyzed for evidence of inflammation, fibrosis, lipogenesis, and apoptosis...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28182612/non-alcoholic-fatty-liver-disease-in-hiv-infection
#7
Juan Macías, Juan A Pineda, Luis M Real
Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking...
January 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28179883/new-microrna-biomarkers-for-drug-induced-steatosis-and-their-potential-to-predict-the-contribution-of-drugs-to-non-alcoholic-fatty-liver-disease
#8
Mireia López-Riera, Isabel Conde, Laia Tolosa, Ángela Zaragoza, José V Castell, María J Gómez-Lechón, Ramiro Jover
Background and Aims: Drug-induced steatosis is a major reason for drug failure in clinical trials and post-marketing withdrawal; and therefore, predictive biomarkers are essential. These could be particularly relevant in non-alcoholic fatty liver disease (NAFLD), where most patients show features of the metabolic syndrome and are prescribed with combined chronic therapies, which can contribute to fatty liver. However, specific biomarkers to assess the contribution of drugs to NAFLD are lacking. We aimed to find microRNAs (miRNAs) responsive to steatotic drugs and to investigate if they could become circulating biomarkers for drug-induced steatosis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28179090/protective-role-of-soluble-receptor-for-advanced-glycation-end-products-in-patients-with-non-alcoholic-fatty-liver-disease
#9
Shira Zelber-Sagi, Federico Salomone, Ilana Kolodkin-Gal, Noam Erez, Assaf Buch, Hanny Yeshua, Muriel Webb, Zamir Halpern, Oren Shibolet
BACKGROUND: Soluble receptor for advanced glycation end-products (sRAGE) exerts protective metabolic effects. AIMS: To identify if sRAGE plays a protective role in NAFLD. METHODS: sRAGE (n=55) and Nε-(Carboxymethyl) lysine (CML) (n=36) serum levels were measured in NAFLD patients. Liver steatosis and fibrosis were non-invasively quantified by the hepatorenal index and the NAFLD fibrosis score (NFS). RESULTS: sRAGE levels were lower in NAFLD patients compared to controls (1207±439 vs...
January 19, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28177674/exercise-restores-bioavailability-of-hydrogen-sulfide-and-promotes-autophagy-influx-in-livers-of-mice-fed-with-high-fat-diet
#10
Bing Wang, Jing Zeng, Qi Gu
In the gold standard treatment for non-alcoholic fatty liver disease (NAFLD), exercise training has been shown to effectively improve NASH. However, limited data are available about the underlying mechanisms involved. This work was undertaken to investigate the mechanisms underlying the beneficial effect of exercise training on high-fat diet (HFD)-induced NAFLD in mice. Male mice were fed with HFD and given moderate-intensity exercise for 24 weeks. Exercise training lowered weight gain, attenuated systemic insulin resistance and glucose intolerance, mitigated hepatic steatosis and fibrosis in mice fed with HFD...
January 10, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28170108/caspase-cleaved-k18-fragments-increase-during-alcohol-withdrawal-and-predict-liver-related-death-in-patients-with-ald
#11
S Mueller, P Nahon, V Rausch, T Peccerella, I Silva, E Yagmur, B K Straub, C Lackner, H K Seitz, P Rufat, A Sutton, H Bantel, T Longerich
Non-invasive assessment of disease activity in patients with non-alcoholic (NALFD) and alcoholic liver disease (ALD) is still unsettled but essential for the evaluation of disease progression. We here studied the association of total (M65) and caspase-cleaved (M30) serum keratin-18 fragments (n=204) with histological parameters (n=106) in heavy drinkers primarily admitted for alcohol withdrawal before and after alcohol detoxification. An age, gender and fibrosis-stage matched NAFLD cohort (n=30) was used for comparison...
February 7, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28169366/phytosterol-esters-attenuate-hepatic-steatosis-in-rats-with-non-alcoholic-fatty-liver-disease-rats-fed-a-high-fat-diet
#12
Lihua Song, Dan Qu, Qing Zhang, Jing Jiang, Haiyue Zhou, Rui Jiang, Yating Li, Yao Zhang, Hongli Yan
Given the adverse effects of drugs used for NAFLD treatment, identifying novel and effective natural compound to prevent NAFLD is urgently needed. In the present study, the effects of phytosterol esters (PSEs) on NAFLD were explored. Adult SD rats were randomized into five groups: normal chow diet (NC), high-fat diet (HF), low-, medium- and high-dose PSE treatment plus high-fat diet groups (PSEL, PSEM, and PSEH). Our results showed that the levels of LDL-C in the PSEL group and hepatic TG, TC, and FFA in the three PSEs groups were significantly decreased...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28159867/fenofibrate-but-not-ezetimibe-prevents-fatty-liver-disease-in-mice-lacking-phosphatidylethanolamine-n-methyltransferase
#13
Jelske N van der Veen, Susanne Lingrell, Xia Gao, Abhijit Takawale, Zamaneh Kassiri, Dennis E Vance, René L Jacobs
BACKGROUND AND AIMS: Mice lacking phosphatidylethanolamine N-methyltransferase (PEMT) are protected from high-fat diet (HFD)-induced obesity and insulin resistance. However, these mice develop severe non-alcoholic fatty liver disease (NAFLD) when fed the HFD, which is mainly due to inadequate secretion of VLDL particles. Our aim was to prevent NAFLD development in mice lacking PEMT. METHODS: We treated Pemt-/- mice with either ezetimibe or fenofibrate to see if either could ameliorate liver disease in these mice...
February 3, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28153708/steroidogenic-acute-regulatory-protein-star-overexpression-attenuates-hfd-induced-hepatic-steatosis-and-insulin-resistance
#14
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)...
January 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28149317/prevalence-of-non-alcoholic-fatty-liver-disease-in-patients-with-coronary-artery-disease
#15
Babak Baharvand-Ahmadi, Khalil Sharifi, Mehrdad Namdari
BACKGROUND: Several common metabolic risk factors contribute to development of both non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD). The aim was to determine prevalence of NAFLD in patients with CAD. METHODS: This prospective study was carried out from December 2011 to June 2012. All patients with documented diagnosis of CAD with stenosis of one of the main coronary arteries or their branches were included in the study. Ultrasound examination of liver was performed in all patients to diagnose hepatic steatosis...
July 2016: ARYA Atherosclerosis
https://www.readbyqxmd.com/read/28144388/hepatic-structural-enhancement-and-insulin-resistance-amelioration-due-to-at1-receptor-blockade
#16
EDITORIAL
Vanessa Souza-Mello
Over the last decade, the role of renin-angiotensin system (RAS) on the development of obesity and its comorbidities has been extensively addressed. Both circulating and local RAS components are up-regulated in obesity and involved in non-alcoholic fatty liver disease onset. Pharmacological manipulations of RAS are viable strategies to tackle metabolic impairments caused by the excessive body fat mass. Renin inhibitors rescue insulin resistance, but do not have marked effects on hepatic steatosis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB) yield beneficial hepatic remodeling...
January 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28144387/from-the-liver-to-the-heart-cardiac-dysfunction-in-obese-children-with-non-alcoholic-fatty-liver-disease
#17
EDITORIAL
Anna Di Sessa, Giuseppina Rosaria Umano, Emanuele Miraglia Del Giudice, Nicola Santoro
In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness...
January 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28142230/compound-k-attenuates-glucose-intolerance-and-hepatic-steatosis-through-ampk-dependent-pathways-in-type-2-diabetic-oletf-rats
#18
Yoo-Cheol Hwang, Da-Hee Oh, Moon Chan Choi, Sang Yeoul Lee, Kyu-Jeong Ahn, Ho-Yeon Chung, Sung-Jig Lim, Sung Hyun Chung, In-Kyung Jeong
Background/Aims: Non-alcoholic fatty liver disease is associated with insulin resistance. Compound K (CK) is the final metabolite of panaxadiol ginsenosides that have been shown to exert antidiabetic effects. However, the molecular mechanism of the antidiabetic effects in the liver have not been elucidated; further, whether CK has beneficial effects in hepatosteatosis remains unclear. Therefore, we evaluated the effect of CK on hepatosteatosis as well as its mechanism in high-fat diet (HFD)-fed type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats...
February 1, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28138103/turning-up-the-heat-against-metabolic-syndrome-and-non-alcoholic-fatty-liver-disease
#19
William T Festuccia
Brown adipose tissue (BAT), an organ specialized in the conversion of chemical energy from nutrients into heat through a process denominated as nonshivering thermogenesis, plays an important role in defence of body weight and homoeothermy in mammals. BAT nonshivering thermogenesis relies on the activity of the uncoupling protein 1 (UCP-1), a mitochondrial protein that, on demand, deviates proton gradient from ATP synthesis to heat generation. Energetically, this process is supported by BAT-elevated mitochondrial density and outstanding capacity to oxidize fatty acids and glucose...
February 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28130788/increased-risk-of-mortality-by-fibrosis-stage-in-non-alcoholic-fatty-liver-disease-systematic-review-and-meta-analysis
#20
Parambir S Dulai, Siddharth Singh, Janki Patel, Meera Soni, Larry J Prokop, Zobair Younossi, Giada Sebastiani, Mattias Ekstedt, Hannes Hagstrom, Patrik Nasr, Per Stal, Vincent Wai-Sun Wong, Stergios Kechagias, Rolf Hultcrantz, Rohit Loomba
BACKGROUND: Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD. METHODS: Through a systematic review and meta-analysis, we identified 5 adult NAFLD cohort studies reporting fibrosis stage specific mortality (0-4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRR) with 95% confidence intervals (CI), for all-cause and liver-related mortality, were estimated...
January 28, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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