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Shahar Azar, Shiri Sherf-Dagan, Alina Nemirovski, Muriel Webb, Asnat Raziel, Andrei Keidar, David Goitein, Nasser Sakran, Oren Shibolet, Joseph Tam, Shira Zelber-Sagi
BACKGROUND: The endocannabinoid (eCB) system plays a key role in the development of obesity and its comorbidities. Limited information exists on the changes in circulating eCBs following bariatric surgery. OBJECTIVES: This study aims to (i) assess the circulating levels of eCBs and related molecules and (ii) examine the association between their levels and numerous clinical/metabolic features pre- and post-operatively. METHODS: Sixty-five morbidly obese patients (age 42...
September 22, 2018: Obesity Surgery
Yuya Urano, Shingo Oda, Koichi Tsuneyama, Tsuyoshi Yokoi
Fasiglifam (TAK-875), a G protein-coupled receptor 40 (GPR40) agonist, was a drug candidate for type 2 diabetes. However, its development was terminated in phase 3 trials due to liver safety concerns. Although TAK-875 was reported to inhibit hepatobiliary transporters such as bile salt export pump (Bsep) and disturb bile acid disposition, pathogenic mechanisms of TAK-875-induced liver injury are not fully understood. In this study, we sought to identify these mechanisms with a hepatic genome-wide transcriptomic analysis in a murine model...
September 20, 2018: Chemico-biological Interactions
Xue-Lian Zheng, Jian-Ping Wu, Yue Gong, Jun-Bo Hong, Hai-Ying Xiao, Jia-Wei Zhong, Bo Xie, Bi-Min Li, Gui-Hai Guo, Xuan Zhu, An-Jiang Wang
Interleukin-25 (IL-25) is a cytokine that has previously been shown to have a protective role against non-alcoholic fatty liver disease (NAFLD), which is associated with the induction of M2 macrophages. However, the direct relationships between IL-25 expression regulation, macrophagic induction, and NAFLD, remain unknown. In this study, we demonstrate that IL-25 promotes hepatic macrophage differentiation into M2a macrophages both in vivo and in vitro via the IL-13/STAT6 pathway. M2 macrophages that were differentiated in vitro were able to ameliorate high-fat diet HFD-induced hepatic steatosis...
September 22, 2018: Immunology and Cell Biology
Takatomo Arai, Masako Tanaka, Nobuhito Goda
Adaptive responses to hypoxia regulate hepatic lipid metabolism, but their consequences in nonalcoholic fatty liver disease (NAFLD) are largely unknown. Here, we show that hypoxia inducible factor-1 (HIF-1), a key determinant of hypoxic adaptations, prevents excessive hepatic lipid accumulation in the progression of NAFLD. When exposed to a choline-deficient diet (CDD) for 4 weeks, the loss of hepatic Hif-1α gene accelerated liver steatosis with enhanced triglyceride accumulation in the liver compared to wild-type (WT) livers...
September 21, 2018: Scientific Reports
Eman M Hasan, Rasha A Abd Al Aziz, Dina Sabry, Samar K Darweesh, Hedy A Badary, Aisha Elsharkawy, Mahmood M Abouelkhair, Ayman Yosry
BACKGROUND AND AIMS: Various genetic polymorphisms play a key-role in the pathogenesis of NAFLD and progression to NASH with fibrosis to cirrhosis. We aimed to study the association between single-nucleotide polymorphisms (SNPs) in NNMT gene, namely rs694539 and the development of different stages of NAFLD diagnosed by controlled attenuation parameter (CAP) of FibroScan Echosens®. METHODS: Transient elastography (FibroScan®) with controlled attenuation parameter (CAP) measurement was performed in 81 NAFLD patients (35 of them with liver biopsy) and 80 non-NAFLD controls...
September 2018: Journal of Gastrointestinal and Liver Diseases: JGLD
Mayra Domínguez-Pérez, Arturo Simoni-Nieves, Patricia Rosales, Natalia Nuño-Lámbarri, Mónica Rosas-Lemus, Verónica Souza, Roxana U Miranda, Leticia Bucio, Salvador Uribe Carvajal, Jens U Marquardt, Daekwan Seo, Luis E Gomez-Quiroz, María Concepción Gutiérrez-Ruiz
Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of histopathological changes ranging from non-inflammatory intracellular fat deposition to non-alcoholic steatohepatitis (NASH), which may progress into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. Recent data suggest that impaired hepatic cholesterol homeostasis and its accumulation are relevant to the pathogenesis of NAFLD/NASH. Despite a vital physiological function of cholesterol, mitochondrial dysfunction is an important consequence of dietary-induced hypercholesterolemia and was, subsequently, linked to many pathophysiological conditions...
September 21, 2018: Journal of Cellular Physiology
Kun Tang, Xiangwu Zheng, Jie Lin, Minghua Zheng, Haixia Lin, Tiancheng Li, Ling Wang
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as an independent risk factor for cardiovascular diseases. However, there were few studies evaluating the condition of myocardial glucose metabolism in patients with NAFLD. Therefore, the aim of this study was to investigate the association between NAFLD and myocardial glucose uptake assessed by using 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) and whether or not alteration of myocardial glucose uptake could be an indicator linking to cardiac dysfunction in NAFLD individuals...
September 20, 2018: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
Xichuan Zhai, Dehui Lin, Yan Zhao, Wenwen Li, Xingbin Yang
This study aimed to investigate the effects of supplementation with bacterial cellulose (BC), konjac glucomannan (KGM) and combined BC/KGM fiber on high-fat (HF)-diet-induced obesity in C57BL/6J mice. The results showed that combined supplementation with BC/KGM in HF-fed mice was more efficient in reducing body weight, lowing serum lipid profiles and suppressing insulin resistance than single supplementation with BC or KGM. Moreover, supplementation with combined BC/KGM fiber more efficiently alleviated HF-diet-induced liver injury by decreasing hepatic steatosis in comparison with supplementation with BC or KGM alone...
September 21, 2018: Food & Function
Safa Kinaneh, Mohammad Agbaria, Niroz Abu-Saleh, Shadi Hamoud
This data article contains analysis of data observed in E0 mice placed on high fat diet, and treated by intraperitoneal injections of either normal saline (control) or the heparanase inhibitor PG545, in two different doses. Mice body weights and food intake were measured weekly and analyzed data are presented in graphs. Data will be of value for further understanding the role of the enzyme heparanase in controlling food intake and body weight. For further interpretations, see please "Heparanase inhibition attenuates atherosclerosis progression and liver steatosis in E0 mice" (Muhammad et al...
October 2018: Data in Brief
Liang Sheng, Lan Ye, Dong Zhang, William P Cawthorn, Bin Xu
Long non-coding RNAs (lncRNA) are emerging as new genetic/epigenetic regulators that can impact almost all physiological functions. Here, we focus on the long non-coding steroid receptor RNA activator (SRA), including new insights into its effects on gene expression, the cell cycle, and differentiation; how these relate to physiology and disease; and the mechanisms underlying these effects. We discuss how SRA acts as an RNA coactivator in nuclear receptor signaling; its effects on steroidogenesis, adipogenesis, and myocyte differentiation; the impact on breast and prostate cancer tumorigenesis; and, finally, its ability to modulate hepatic steatosis through several signaling pathways...
2018: Frontiers in Medicine
Ji Hye Han, Jung Heun Ju, Yong Sun Lee, Ju Ho Park, In Jun Yeo, Mi Hee Park, Yoon Seok Roh, Sang Bae Han, Jin Tae Hong
Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have broader functions including potent antioxidant, anti-inflammatory and neuroprotective properties. Considerable researches have demonstrated that AXT shows preventive and therapeutic properties against for Diabetes, Osteoarthritis and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease has not yet been reported. In this study, we investigated effects of AXT on ethanol-induced liver injury in chronic plus binge alcohol feeding model...
September 20, 2018: Scientific Reports
Xiaofang Sun, Wei Li, Yujie Deng, Bingzi Dong, Ying Sun, Yu Xue, Yangang Wang
The liver is a central metabolic organ. Activating transcription factor 6 (ATF6) acts as an ER stress responsive gene and is reported to attenuate hepatic steatosis. Over expressing a dominant-negative form of ATF6 exacerbates glucose intolerance and insulin resistance. In the present study, we used the conditional knockout technique to specifically knockout ATF6 in the mouse liver. We used qPCR to detect the mRNA levels of related genes. Western blot analysis was used to evaluate protein levels. Flow cytometry assay showed the apoptosis status...
September 17, 2018: Biochemical and Biophysical Research Communications
Anika Nier, Annette Brandt, Ina Barbara Conzelmann, Yelda Özel, Ina Bergheim
The role of nutrition and diet in the development of non-alcoholic fatty liver disease (NAFLD) is still not fully understood. In the present study, we determined if dietary pattern and markers of intestinal permeability differ between overweight children with and without NAFLD. In addition, in a feasibility study, we assessed the effect of a moderate dietary intervention only focusing on nutrients identified to differ between groups on markers of intestinal barrier function and health status. Anthropometric data, dietary intake, metabolic parameters, and markers of inflammation, as well as of intestinal permeability, were assessed in overweight children ( n = 89, aged 5⁻9) and normal-weight healthy controls ( n = 36, aged 5⁻9)...
September 19, 2018: Nutrients
Chian-Jiun Liou, Ciao-Han Wei, Ya-Ling Chen, Ching-Yi Cheng, Chia-Ling Wang, Wen-Chung Huang
BACKGROUND/AIMS: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro...
September 20, 2018: Cellular Physiology and Biochemistry
Chloe Hutton, Michael L Gyngell, Matteo Milanesi, Alexandre Bagur, Michael Brady
PURPOSE: Several studies have demonstrated the accuracy, precision, and reproducibility of proton density fat fraction (PDFF) quantification using vendor-specific image acquisition protocols and PDFF estimation methods. The purpose of this work is to validate a confounder-corrected, cross-vendor, cross field-strength, in-house variant LMS IDEAL of the IDEAL method licensed from the University of Wisconsin, which has been developed for routine clinical use. METHODS: LMS IDEAL is implemented using a combination of patented and/or published acquisition and some novel model fitting methods required to correct confounds which result from the imaging and estimation processes, including: water-fat ambiguity; T2* relaxation; multi-peak fat modelling; main field inhomogeneity; T1 and noise bias; bipolar readout gradients; and eddy currents...
2018: PloS One
Nahir Cortes-Santiago, Daniel H Leung, Eumenia Castro, Milton Finegold, Hao Wu, Kalyani Patel
OBJECTIVES: Systematic study of allograft liver histology in children undergoing orthotopic liver transplantation (LT) for cystic fibrosis-related liver disease (CFLD). METHODS: Retrospective clinicopathologic review of explants and allograft liver biopsies from 13 children and adolescents with CFLD. RESULTS: In this study, the median age at LT for CFLD was 15.7 years. Notably, 10 of 13 (77%) CF explants had >5% steatosis and 8 of 13 (61...
September 18, 2018: Journal of Pediatric Gastroenterology and Nutrition
Teruki Miyake, Sakiko Yoshida, Shinya Furukawa, Takenori Sakai, Fujimasa Tada, Hidenori Senba, Shin Yamamoto, Yohei Koizumi, Osamu Yoshida, Masashi Hirooka, Teru Kumagi, Tetsuju Niiya, Hiroaki Miyaoka, Abe Masanori, Bunzo Matsuura, Yoichi Hiasa
Background: There are few effective medications for non-alcoholic steatohepatitis (NASH). We investigated the efficacy of ipragliflozin (selective sodium-glucose cotransporter-2 inhibitor [SGLT2I]) for the treatment of patients with type 2 diabetes mellitus (T2DM) complicated by non-alcoholic fatty liver disease (NAFLD). Methods: We prospectively enrolled patients with T2DM complicated by NAFLD treated at our institutions from January 2015 to December 2016. Patients received oral ipragliflozin (50 mg/day) once daily for 24 weeks...
2018: Open Medicine (Warsaw, Poland)
Yanmei Li, Bingyuan Huang, Xiang Jiang, Weihua Chen, Jun Zhang, Yiran Wei, Yong Chen, Min Lian, Zhaolian Bian, Qi Miao, Yanshen Peng, Jingyuan Fang, Qixia Wang, Ruqi Tang, M Eric Gershwin, Xiong Ma
Mucosal-associated invariant T (MAIT) cells, a novel population of innate-like lymphocytes, have been involved in various inflammatory and autoimmune diseases. However, their role in the development of nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated the alterations of phenotype and immunological function of MAIT cells in NAFLD. Analysis of PBMCs in 60 patients with NAFLD and 48 healthy controls (HC) revealed that circulating MAIT cell frequency decreased in NAFLD, especially in the patients with higher serum levels of γ-glutamyl transferase or total triglyceride...
2018: Frontiers in Immunology
Stephanie T Chung, Amber B Courville, Anthony U Onuzuruike, Mirella Galvan-De La Cruz, Lilian S Mabundo, Christopher W DuBose, Kannan Kasturi, Hongyi Cai, Ahmed M Gharib, Peter J Walter, H Martin Garraffo, Shaji Chacko, Morey W Haymond, Anne E Sumner
Black women, compared with White women, have high rates of whole-body insulin resistance but a lower prevalence of fasting hyperglycemia and hepatic steatosis. This dissociation of whole-body insulin resistance from fasting hyperglycemia may be explained by racial differences in gluconeogenesis, hepatic fat, or tissue-specific insulin sensitivity. Two groups of premenopausal federally employed women, without diabetes were studied. Using stable isotope tracers, [2H2O] and [6,62-H2]glucose, basal glucose production was partitioned into its components (gluconeogenesis and glycogenolysis) and basal whole-body lipolysis ([2H5]glycerol) was measured...
September 20, 2018: JCI Insight
Arinc Ozturk, Joseph R Grajo, Michael S Gee, Alex Benjamin, Rebecca E Zubajlo, Kai E Thomenius, Brian W Anthony, Anthony E Samir, Manish Dhyani
Non-alcoholic fatty liver disease is a condition that is characterized by the presence of >5% fat in the liver and affects more than one billion people worldwide. If adequate and early precautions are not taken, non-alcoholic fatty liver disease can progress to cirrhosis and death. The current reference standard for detecting hepatic steatosis is a liver biopsy. However, because of the potential morbidity associated with liver biopsies, non-invasive imaging biomarkers have been extensively investigated. Magnetic resonance imaging-based methods have proven accuracy in quantifying liver steatosis; however, these techniques are costly and have limited availability...
September 16, 2018: Ultrasound in Medicine & Biology
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