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Nonalcoholic hepatic steatosis

Oren Rom, Guan Xu, Yanhong Guo, Yunhao Zhu, Huilun Wang, Jifeng Zhang, Yanbo Fan, Wenying Liang, Haocheng Lu, Yuhao Liu, Michael Aviram, Zhipeng Liu, Seongho Kim, Wanqing Liu, Xueding Wang, Y Eugene Chen, Luis Villacorta
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are reaching global epidemic proportions. Lack of non-invasive diagnostic tools and effective therapies constitute two of the major hurdles for a bona fide treatment and a reversal of NASH progression and/or regression of the disease. Nitro-oleic acid (OA-NO2 ) has been proven effective in multiple experimental models of inflammation and fibrosis. Thus, the potential benefit of in vivo administration of OA-NO2 to treat advanced NAFLD was tested herein in a model of long-term NASH diet-induced liver damage...
February 13, 2019: EBioMedicine
Barbara Ulmasov, Hidenao Noritake, Peter Carmichael, Kiyoko Oshima, David W Griggs, Brent A Neuschwander-Tetri
The presence and stage of liver fibrosis in patients with nonalcoholic steatohepatitis (NASH) is strongly associated with mortality. Thus, both preventing and reversing fibrosis are critically important approaches to prevent death or the need for liver transplantation from NASH. Recently, fibrosis in several mouse models of organ injury was shown to be prevented and reversed with the potent small molecule, arginine-glycine-aspartic acid tripeptide (RGD)-binding, integrin antagonist (3S)-3-(3-bromo-5-(tert-butyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid (Center for World Health and Medicine [CWHM]-12)...
February 2019: Hepatology Communications
Lisa Katharina Maresch, Pia Benedikt, Ursula Feiler, Sandra Eder, Kathrin A Zierler, Ulrike Taschler, Stephanie Kolleritsch, Thomas O Eichmann, Gabriele Schoiswohl, Christina Leopold, Beatrix I Wieser, Caroline Lackner, Thomas Rülicke, Jan van Klinken, Dagmar Kratky, Tarek Moustafa, Gerald Hoefler, Guenter Haemmerle
Murine hepatic carboxylesterase 2c ( Ces2c ) and the presumed human ortholog carboxylesterase 2 ( CES2 ) have been implicated in the development of nonalcoholic fatty liver disease (NAFLD) in mice and obese humans. These studies demonstrated that Ces2c hydrolyzes triglycerides (TGs) in hepatocytes. Interestingly, Ces2c / CES2 is most abundantly expressed in the intestine, indicating a role of Ces2c / CES2 in intestinal TG metabolism. Here we show that Ces2c is an important enzyme in intestinal lipid metabolism in mice...
February 2019: Hepatology Communications
Gil Ben-Yakov, Hawwa Alao, John P Haydek, Nancy Fryzek, Min Ho Cho, Mehdi Hemmati, Vikram Samala, Margaret Shovlin, Kieron Dunleavy, Wyndham Wilson, Elizabeth C Jones, Yaron Rotman
Nonalcoholic fatty liver disease is the most common liver disorder in the developed world. Although typically reflecting caloric overload, it can also be secondary to drug toxicity. We aimed to describe the incidence and risk factors for de novo steatosis during chemotherapy for non-Hodgkin lymphoma (NHL). In this retrospective case-control study, adult patients with NHL were treated with rituximab, cyclophosphamide, doxorubicin, prednisone, and vincristine (R-CHOP) or R-CHOP + etoposide (EPOCH-R). Patients with liver disease or steatosis were excluded...
February 2019: Hepatology Communications
Ram V Nampoothiri, Ajay Duseja, Manish Rathi, Swastik Agrawal, Naresh Sachdeva, Manu Mehta, Harpal S Dhaliwal, Radha K Dhiman, Yogesh Chawla
Background and aims: There is sparse data on the prevalence of renal dysfunction in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the presence of renal dysfunction in patients with NAFLD and correlate it with the severity of liver disease. Methods: One hundred nonalcoholic patients with ultrasound showing hepatic steatosis were enrolled into the study after exclusion of other causes. Presence of renal dysfunction was estimated by glomerular filtration rate and by evaluating 24 h urinary protein and microalbumin...
January 2019: Journal of Clinical and Experimental Hepatology
Lijun Wang, Chenghe Ding, Fangfang Zeng, Huilian Zhu
β-Carotene has been reported to alleviate hepatic steatosis (SS), inflammation, and fibrosis in vivo and vitro studies. However, the clinical relevance of serum β-carotene and β-carotene-to-retinol (SC/SR) ratio with histological severity in nonalcoholic fatty liver disease (NAFLD) patients is unknown. This case-control study enrolled 24 control subjects and 62 NAFLD patients. Liver biopsies were collected and histological characteristics were assessed. Information with regard to demographic, anthropometric and dietary intake was assessed by face-to-face interviews with questionnaire...
February 13, 2019: Annals of Nutrition & Metabolism
Jingjing Tong, Cui-Juan Han, Jia Zhen Zhang, Wen-Zhi He, Guo-Jun Zhao, Xu Cheng, Lei Zhang, Ke-Qiong Deng, Ye Liu, Hui-Fen Fan, Song Tian, Jingjing Cai, Zan Huang, Zhi-Gang She, Peng Zhang, Hongliang Li
Nonalcoholic fatty liver disease (NAFLD) has become a worldwide epidemic. A large and growing unmet therapeutic need has inspired numerous studies in the field. Integrating the published genomic data available in the Gene Expression Omnibus with NAFLD samples from rodents, we discovered that interferon regulatory factor 6 (IRF6) is significantly suppressed in high-fat diet (HFD)-induced fatty liver. In the current study, we identified IRF6 in hepatocytes as a protective factor in liver steatosis. During HFD challenge, hepatic Irf6 was suppressed by promoter hypermethylation...
February 12, 2019: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Menghua Li, Wei Chen, Lili Wang, Jialin Sun, Lei Zhou, Yucong Shi, Chuhan Wang, Bohua Zhong, Weiguo Shi, Zhongwu Guo
Nonalcoholic fatty liver disease (NAFLD) is a very common chronic hepatic disease, with nonalcoholic steatohepatitis (NASH) as a major and severe subcategory that can lead to cirrhosis and hepatocellular carcinoma, thereby a high mortality rate. Currently, there has been no approved drug to treat NAFLD or NASH. The current study has presented RLA8, a novel and balanced quadruple agonist for hepatic lipid metabolism and inflammation-related peroxisome proliferator-activated receptors (PPARs)-α/γ/δ and G-protein-coupled receptor 40 (GPR40), as a NASH drug candidate...
February 11, 2019: Journal of Pharmacology and Experimental Therapeutics
Shoji Kawauchi, Sayo Horibe, Naoto Sasaki, Toshihito Tanahashi, Shigeto Mizuno, Tsuneo Hamaguchi, Yoshiyuki Rikitake
Nonalcoholic steatohepatitis (NASH) progresses from nonalcoholic fatty liver disease (NAFLD); however, efficacious drugs for NASH treatment are lacking. Sodium alginate (SA), a soluble dietary fiber extracted from brown algae, could protect the small intestine from enterobacterial invasion. NASH pathogenesis has been suggested to be associated with enterobacterial invasion, so we examined the effect of SA on methionine- and choline-deficient (MCD) diet-induced steatohepatitis in mice (the most widely-used model of NASH)...
February 9, 2019: Marine Drugs
Sorim Choung, Ji Min Kim, Kyong Hye Joung, Eaum Seok Lee, Hyun Jin Kim, Bon Jeong Ku
Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disease. NAFLD begins with excessive lipid accumulation in the liver and progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is closely linked to dysregulated hepatic lipid metabolism. Although recent studies have reported that epidermal growth factor receptor (EGFR) signaling regulates lipid metabolism, the roles of EGFR and EGFR inhibitors as modulators of lipid metabolism are largely unknown. Here, we investigated whether inhibiting EGFR using the EGFR tyrosine kinase inhibitor (TKI) PD153035 improves NAFLD...
2019: PloS One
Yang Li, Luping Ren, Guangyao Song, Pu Zhang, Liying Yang, Xinwei Chen, Xiaolei Yu, Shuchun Chen
BACKGROUND: Autophagy was recently regarded as a potential mechanism in nonalcoholic fatty liver disease. Silibinin (SIL), a natural flavonoid, has been used to prevent nonalcoholic fatty liver disease, however, the underlying mechanism is unclear. The aim of the present study was to explore the effect of SIL on hepatic steatosis and the possible link with autophagy. METHODS: The degree of hepatic steatosis in HepG2 cells was observed by oil-red O staining and triglyceride content...
February 7, 2019: Endocrine, Metabolic & Immune Disorders Drug Targets
Li-Li Dai, Shu-De Li, Yi-Cheng Ma, Jun-Rui Tang, Jun-Yan Lv, Yuan-Qing Zhang, Ying-Lei Miu, Yan-Qiong Ma, Chun-Mei Li, Yi-You Chu, Kun-Hua Wang, Lan-Qing Ma, Cheng-Gang Zou
BACKGROUND & AIMS: Insulin resistance is strongly associated with nonalcoholic fatty liver disease, a chronic, obesity-related liver disease. Increased endoplasmic reticulum stress plays an important role in the development of insulin resistance. In this study, we investigated the roles of miRNAs in regulating ER stress in the liver of rats with obesity. METHODS: We used miRNA microarray to determine the miRNA expression profiles in the liver of rats fed a high fat diet (HFD)...
February 5, 2019: Liver International: Official Journal of the International Association for the Study of the Liver
Johanna Nattenmüller, Christopher L Schlett, Nanae Tsuchiya, Scott B Reeder, Perry J Pickhardt, Harald Kramer, Hans-Ulrich Kauczor, Mark O Wielpütz, Joon B Seo, Hiroto Hatabu, Edwin J R van Beek, Mark L Schiebler
The purpose of this review article is to acquaint the reader with the current state of the art for the noncardiovascular imaging biomarkers of metabolic syndrome found on noncontrast computed tomography (NCCT) of the chest and their prognostic significance. Routine chest NCCT includes quantitative information with regard to tissue density and organ volumes in the neck, chest, and upper abdomen. The specific imaging biomarkers that may be seen in association with metabolic syndrome include low thyroid iodine organification, hepatic steatosis, sarcopenia (muscle volume and density), demineralization of the thoracic and upper lumbar vertebral bodies, loss of axial skeletal muscle mass, premature lung inflammation, and an increased deposition of subcutaneous and visceral fat...
January 31, 2019: Journal of Thoracic Imaging
Hsin-Hsien Yu, Mao-Chih Hsieh, Szu-Yuan Wu, Edgar D Sy, Yan-Shen Shan
Background: Duodenal-jejunal bypass (DJB) is an important component of many types of current bariatric surgery including Roux-en-Y gastric bypass, mini-gastric bypass, biliopancreatic diversion, duodenal switch, and DJB plus sleeve gastrectomy. Surgery is often observed to ameliorate nonalcoholic steatohepatitis (NASH), but without a clearly delineated mechanism. In this study, we investigated the effects of DJB in diet-induced obese rats with NASH. Materials and methods: Male Wistar rats were divided into four groups and fed the following diets over 6 months: A) normal chow (NC group, n=6); B) methionine-choline-deficient (MCD)-high-fat (HF) diet (HF group, n=6); C) MCD-HF diet for 3 months followed by DJB and MCD-HF diet for subsequent 3 months (DJB group, n=6); and D) MCD-HF diet for 3 months followed by treatment with pioglitazone (PGZ) with MCD-HF diet for subsequent 3 months (PGZ group, n=6)...
2019: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Atsuko Kamiya, Takeshi Hara, Masayuki Tsuda, Emi Tsuru, Yasushi Kuroda, Urara Ota, Takashi Karashima, Hideo Fukuhara, Keiji Inoue, Masahiro Ishizuka, Motowo Nakajima, Tohru Tanaka
5-Aminolevulinic acid, a natural amino acid, activates mitochondrial respiration and induces heme oxygenase-1 expression. Obesity and type 2 diabetes mellitus are associated with age-related mitochondrial respiration defect, oxidative stress and inflammation. The aim of this study is to investigate the effects of 5-aminolevulinic acid with sodium ferrous citrate on early renal damage and hepatic steatosis. 7-Month-old C57BL/6 mice were fed with a standard diet or high fat diet for 9 weeks, which were orally administered 300 mg/kg 5-aminolevulinic acid combined with 47 mg/kg sodium ferrous citrate (5-aminolevulinic acid/sodium ferrous citrate) or vehicle for the last 5 weeks...
January 2019: Journal of Clinical Biochemistry and Nutrition
A A Shipovskaya, O P Dudanova
AIM: To determine the frequency of intrahepatic cholestasis and its impact on the clinical features of the different forms of non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: The study involved 163 patients with NAFLD: 92 (56.4%) with hepatic steatosis (HS), 56 (34.4%) with steatohep- atitis (SH) and 15 (9.2%) with liver cirrhosis (LC). Diagnosis is based on clinical, laboratory, ultrasound and histological data. Insulin, tu- mor necrosis factor α (TNF-α), fragments of cytokeratin-18 (FCK-18) were determined by ELISA...
February 15, 2018: Terapevticheskiĭ Arkhiv
Yoshiko Nakamura, Masanori Abe, Keitarou Kawasaki, Teruki Miyake, Takao Watanabe, Osamu Yoshida, Masashi Hirooka, Bunzo Matsuura, Yoichi Hiasa
Obesity-induced adipose-tissue dysfunction is a critical contributor to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). B cell-activating factor (BAFF) is an adipokine related to impaired insulin sensitivity, and the serum BAFF concentration is associated with NAFLD severity. In this study, we aimed to determine the direct in vivo role of BAFF in the development of insulin resistance, adipocyte dysfunction, and hepatic steatosis using BAFF-/- mice fed a high-fat diet (HFD). HFD-fed BAFF-/- mice exhibited significantly improved insulin sensitivity despite their increased weight gain and adiposity relative to HFD-fed wild-type mice...
January 30, 2019: Scientific Reports
Karn Wijarnpreecha, Melissa Scribani, Donghee Kim, W Ray Kim
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries. Smoking and diabetes mellitus (DM) have been shown to increase mortality, however, whether NAFLD adds to the detrimental effect of smoking in DM and non-DM patients is unknown. We evaluated the possible interactive effect of NAFLD and smoking on mortality risk in a U.S. population-based sample. METHODS: Cross-sectional data from 11,205 participants in the third National Health and Nutrition Examination Survey were analyzed...
January 29, 2019: Liver International: Official Journal of the International Association for the Study of the Liver
Donghee Kim, Won Kim, Adeyinka C Adejumo, George Cholankeril, Sean P Tighe, Robert J Wong, Stevan A Gonzalez, Stephen A Harrison, Zobair M Younossi, Aijaz Ahmed
BACKGROUND AND AIM: Advanced fibrosis associated with nonalcoholic fatty liver disease (NAFLD) has been reported to have a higher risk of hepatic and non-hepatic mortality. We aim to study the recent trends in the prevalence of NAFLD-related advanced fibrosis in a large population sample. METHODS: Cross-sectional data from 28,739 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2016 were utilized. NAFLD was defined using the hepatic steatosis index (HSI) and the US fatty liver index (USFLI) in the absence of other causes of chronic liver disease...
January 29, 2019: Hepatology International
Jacopo Troisi, Federica Belmonte, Antonella Bisogno, Luca Pierri, Angelo Colucci, Giovanni Scala, Pierpaolo Cavallo, Claudia Mandato, Antonella Di Nuzzi, Laura Di Michele, Anna Pia Delli Bovi, Salvatore Guercio Nuzio, Pietro Vajro
Pediatric obesity-related metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are increasingly frequent conditions with a still-elusive diagnosis and low-efficacy treatment and monitoring options. In this study, we investigated the salivary metabolomic signature, which has been uncharacterized to date. In this pilot-nested case-control study over a transversal design, 41 subjects (23 obese patients and 18 normal weight (NW) healthy controls), characterized based on medical history, clinical, anthropometric, and laboratory data, were recruited...
January 26, 2019: Nutrients
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