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Aleksandra Derra, Martyna Bator, Tomasz Menżyk, Michał Kukla
Nonalcoholic fatty liver disease (NAFLD) is intrahepatic ectopic lipid deposition which is present despite a lack of other causes of secondary hepatic fat accumulation. It is the most common chronic liver disorder in the welldeveloped countries. NAFLD is a multidisciplinary disease that affects various systems and organs and is inextricably linked to simple obesity, metabolic syndrome, insulin resistance and overt diabetes mellitus type 2. The positive energy balance related to obesity leads to a variety of systemic changes including modified levels of insulin, insulin- like growth factor-1, adipokines, hepatokines and cytokines...
June 2018: Clinical and Experimental Hepatology
Danielle M Fernandes, Vivek Pantangi, Muhammad Azam, Marcela Salomao, Alina C Iuga, Jay H Lefkowitch, James Gill, Raffaella Morotti, Joel E Lavine, Ali A Mencin
OBJECTIVE: To assess the prevalence and severity of nonalcoholic liver disease (NAFLD) in children in a diverse population sample in New York City. STUDY DESIGN: Liver specimens were examined from children 2-19 years old who died of unexpected causes within 48 hours of medical presentation and underwent autopsy in New York City from 2005 to 2010. Records were reviewed for age, sex, weight, height, and race. Two hepatopathologists evaluated each liver specimen to determine pathologic diagnosis...
June 11, 2018: Journal of Pediatrics
Tracey G Simon, Kathleen E Corey, Christopher P Cannon, Michael Blazing, Jeong-Gun Park, Michelle L O'Donoghue, Raymond T Chung, Robert P Giugliano
OBJECTIVE: The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of unique metabolic risk indicators that may accurately predict residual cardiovascular (CV) risk in patients with established coronary disease and metabolic dysfunction. METHODS: We applied the NFS prospectively to 14,819 post-ACS patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), in the IMPROVE-IT trial, using validated NFS cutoffs. The primary endpoint included CV death, myocardial infarction, unstable angina, revascularization or stroke...
May 26, 2018: International Journal of Cardiology
Xiaochao Song, Chunli Song, Li Fan, Qinghua Ma, Jianliang Mao, Wenxin Xu, Xinli Li
OBJECTIVE: To explore the association of silent information regulator 1( SIRT1) rs12778366 and apolipoprotein C3( APOC3) rs2854116 gene polymorphisms with the susceptibility of nonalcoholic fatty liver disease( NAFLD). METHODS: One hundred and thirty two NAFLD patients and 252 healthy controls were enrolled in our present study according to the ultrasound diagnosis and physical examination. Venousblood samples were obtained in the morning after an overnight fast, and the samples were used to analyze the biochemical index, relating to hepatic enzymes, blood lipid and blood glucose metabolism...
July 2017: Wei Sheng Yan Jiu, Journal of Hygiene Research
Lisanne L Blauw, Zhuang Li, Sander S Rensen, Jan Willem M Greve, Aswin Verhoeven, Rico J Derks, Martin Giera, Yanan Wang, Patrick C N Rensen
BACKGROUND AND AIMS: We recently showed that plasma cholesteryl ester transfer protein (CETP) is mainly derived from VSIG4-positive Kupffer cells. Activation of these cells by the bacterial endotoxin lipopolysaccharide (LPS) strongly decreases CETP expression. As Kupffer cell activation plays a detrimental role in the progression of non-alcoholic fatty liver disease (NAFLD), we aimed to study if metabolic liver inflammation is also associated with a decrease in hepatic and circulating CETP...
June 7, 2018: Atherosclerosis
Banrida Wahlang, Craig McClain, Shirish Barve, Leila Gobejishvili
Liver disease is a significant health problem worldwide with mortality reaching around 2 million deaths a year. Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the major causes of chronic liver disease. Pathologically, NAFLD and ALD share similar patterns of hepatic disorders ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis. It is becoming increasingly important to identify new pharmacological targets, given that there is no FDA-approved therapy yet for either NAFLD or ALD...
June 11, 2018: Cellular Signalling
Zhe Wu, Jiang Tan, Yujing Chi, Feng Zhang, Jun Xu, Yang Song, Xu Cong, Na Wu, Yulan Liu
Visceral adipose tissue (VAT) is related to non-alcoholic fatty liver disease (NAFLD). However, the role of mesenteric adipose tissue (MAT), part of the VAT, in NAFLD is unclear. In the present study, we monitored the liver and four depots of the VAT in high fat diet (HFD) feeding mice at multiple time points (4, 8, and 12 weeks). The MAT had become inflamed by the 8th week of HFD feeding, earlier than other depots of VAT. Furthermore, MAT removal after 8 weeks of HFD resulted in more severe steatosis and more foci of inflammation infiltration, as well as higher NAFLD activity scores...
June 14, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Tim Mitchell, Gary P Jeffrey, Bastiaan de Boer, Gerry MacQuillan, George Garas, Helena Ching, Jeffrey Hamdorf, Leon A Adams
INTRODUCTION: It is unclear whether low levels of alcohol are harmful in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether quantity, binge pattern consumption, or type of alcohol was associated with liver fibrosis in patients with NAFLD. METHODS: Previous and current alcohol consumption was assessed in NAFLD patients undergoing liver biopsy. All subjects currently consumed <210 g per week (male) or <140 g per week (female)...
June 14, 2018: American Journal of Gastroenterology
Shihua Wang, Meiqian Xu, Xiaoxia Li, Xiaodong Su, Xian Xiao, Armand Keating, Robert Chunhua Zhao
BACKGROUND: The initiation and progression of hepatocellular carcinoma (HCC) are largely dependent on its local microenvironment. Adipocytes are an important component of hepatic microenvironment in nonalcoholic fatty liver disease (NAFLD), which is a significant risk factor for HCC. Given the global prevalence of NAFLD, a better understanding of the interplay between HCC cells and adipocytes is urgently needed. Exosomes, released by malignant cells, represent a novel way of cell-cell interaction and have been shown to play an important role in cancer cell communication with their microenvironment...
June 14, 2018: Journal of Hematology & Oncology
Liang Xu, Naoto Nagata, Tsuguhito Ota
Obesity is a low-grade sustained inflammatory state that causes oxidative stress in different metabolic tissues, which leads to insulin resistance and nonalcoholic fatty liver disease (NAFLD). Particularly, obesity-induced metabolic endotoxemia plays an important role in the pathogenesis of insulin resistance and inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of antioxidant signaling that serves as a primary cellular defense against the cytotoxic effects of oxidative stress...
June 14, 2018: Adipocyte
Lei Pei, Ting Wan, Sufan Wang, Mingtong Ye, Yun Qiu, Rui Jiang, Nengzhi Pang, Yuanling Huang, Yujia Zhou, Xuye Jiang, Wenhua Ling, Zhenfeng Zhang, Lili Yang
AIM: Cyanidin-3-O-β-glucoside (Cy-3-G) the most abundant monomer of anthocyanins has multiple protective effects on many diseases. To date, whether Cy-3-G could regulate the function of brown adipose tissue (BAT) is still unclear and whether this regulation could influence the secretion of adipokines from BAT to prevent non-alcoholic fatty liver disease (NAFLD) indirectly remains to be explored. In this study we investigated the effect of Cy-3-G on BAT and the potential role of Cy-3-G to prevent fatty liver through regulating the secretion of BAT...
June 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Toshihiro Umehara
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been reported to have a negative effect on bone mineral density (BMD) in Asian populations. Whether such an association exists in Western populations is less clear. METHODS: This cross-sectional analysis of data from NHANES III, a United States national health survey conducted from 1988 to 1994, included 6089 participants aged 40-75 years, selected after excluding people with hepatitis virus serology, elevated alcohol consumption, decreased renal function, or steroid use, and pregnant females...
2018: PloS One
Subhadeep Palit, Sanghamitra Mukherjee, Sougata Niyogi, Anindyajit Banerjee, Dipendu Patra, Amit Chakraborty, Saikat Chakrabarti, Partha Chakrabarti, Sanjay Dutta
Non-alcoholic fatty liver disease (NAFLD) characterized by excess accumulation of triglyceride in hepatocyte is the major cause of chronic liver disease worldwide and no approved drug is available. The mechanistic target of rapamycin complexes (mTORC) have been implicated to promote lipogenesis and fat accumulation in liver and thus serve as attractive drug targets. Generation of no or low cytotoxic mTOR inhibitors are required as the existing cytotoxic mTOR inhibitors are not useful for NAFLD therapy. We have synthesized novel compounds based on the privileged ATP site binder quinoline scaffold conjugated to glucose and galactosamine derivatives that have significantly low cytotoxicity yet having strong mTORC1 inhibitory activity at low micromolar concentrations...
June 13, 2018: Chembiochem: a European Journal of Chemical Biology
Makoto Takeda, Takanori Sakaguchi, Takanori Hiraide, Yasushi Shibasaki, Yoshifumi Morita, Hirotoshi Kikuchi, Koji Ikegami, Mitsutoshi Setou, Hiroyuki Konno, Hiroya Takeuchi
The molecular features of hepatocellular carcinoma arising from non-alcoholic fatty liver disease (NAFLD-HCC) are not well known. In this study, we investigated the mechanism by which NAFLD-HCC survives in a fat-rich environment. We found that caveolin (CAV)-1 was overexpressed in clinical specimens from NAFLD-HCC patients. HepG2, HLE, and HuH-7 HCC cell lines showed decreased proliferation in the presence of the saturated fatty acids palmitic acid and stearic acid, although only HLE cells expressed high levels of CAV-1...
June 13, 2018: Cancer Science
Mohammad Shafi Kuchay, Sonal Krishan, Sunil Kumar Mishra, Khalid Jamal Farooqui, Manish Kumar Singh, Jasjeet Singh Wasir, Beena Bansal, Parjeet Kaur, Ganesh Jevalikar, Harmendeep Kaur Gill, Narendra Singh Choudhary, Ambrish Mithal
OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have been shown to reduce liver fat in rodent models. Data regarding the effect of SGLT-2 inhibitors on human liver fat are scarce. This study examined the effect of empagliflozin (an SGLT-2 inhibitor) on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) by using MRI-derived proton density fat fraction (MRI-PDFF). RESEARCH DESIGN AND METHODS: Fifty patients with type 2 diabetes and NAFLD were randomly assigned to either the empagliflozin group (standard treatment for type 2 diabetes plus empagliflozin 10 mg daily) or the control group (standard treatment without empagliflozin) for 20 weeks...
June 12, 2018: Diabetes Care
Laura Gartmann, Thomas Wex, Kurt Grüngreiff, Dirk Reinhold, Thomas Kalinski, Peter Malfertheiner, Kerstin Schütte
INTRODUCTION: Dysregulation of both, systemic zinc levels and tissue-specific zinc transporters, is reported in chronic inflammatory and malignant liver disease (hepatocellular carcinoma, HCC). Aim of this study is to assess the expression level of three zinc transporters in liver tissue and HCC: ZIP4, ZIP14 and ZnT9. METHODS: The study is based on tissue samples obtained from 138 patients with histologically proven HCC. Tissue specimens from tumor (n = 138) and extra-lesional specimens (n = 72) were assessed immunohistochemically for the expression of the three zinc transporters...
September 2018: Journal of Trace Elements in Medicine and Biology
Eva Juárez-Hernández, Norberto C Chávez-Tapia, Diana C Brizuela-Alcántara, Misael Uribe, Martha H Ramos-Ostos, Natalia Nuño-Lámbarri
INTRODUCTION AND AIM: Nonalcoholic fatty liver disease (NAFLD) is closely associated with overweight and obesity, becoming one of the most prevalent hepatic diseases nowadays. Circulating hemoglobin (Hb) concentration is significantly higher in people with NAFLD, compared to healthy patients. While liver biopsy remains the gold standard for NAFLD diagnosis, it is not the best technique due to adverse events that may occur. Therefore it is important to find less invasive and more sensitive markers...
July 2018: Annals of Hepatology
Emmanuel A Tsochatzis, Philip N Newsome
Non-alcoholic fatty liver disease (NAFLD) has a prevalence of 25-30% in unselected populations and has become the main reason for referrals to hepatology services. From the perspective of liver disease, NAFLD has a high prevalence but low severity. Screening studies in people at risk for NAFLD have shown a prevalence of advanced fibrosis of 5%, which underlines the need for robust pathways for risk stratification in primary care, with subsequent referrals as required. In this Review, we discuss the interface between primary and secondary care with regards to risk stratification and management of patients with NAFLD...
July 2018: Lancet. Gastroenterology & Hepatology
Saba Sayari, Hassan Neishaboori, Maryam Jameshorani
Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases in recent years. The aim of this study was to evaluate the effects of sitagliptin with and without a synbiotic supplement in the treatment of patients with NAFLD. Methods: In total, 138 NAFLD patients aged 18-60 years were enrolled in the study. Patients were randomized to one of the following treatments for 16 weeks: Group I (n=68), sitagliptin 50 mg daily plus placebo (one capsule per day) or group II (n=70) sitagliptin 50 mg daily plus synbiotic (one capsule per day)...
June 12, 2018: Clinical and Molecular Hepatology
Antonella Lascala, Concetta Martino, Maddalena Parafati, Raffaele Salerno, Manuela Oliverio, Daniela Pellegrino, Vincenzo Mollace, Elzbieta Janda
Autophagy dysfunction has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Natural compounds present in bergamot polyphenol fraction (BPF) prevent NAFLD and induce autophagy in rat livers. Here, we employed HepG2 cells expressing DsRed-LC3-GFP, a highly sensitive model system to screen for proautophagic compounds present in BPF. BPF induced autophagy in a time- and dose-dependent fashion and the effect was amplified in cells loaded with palmitic acid. Autophagy was mediated by the hydrophobic fraction of acid-hydrolyzed BPF (A-BPF), containing six flavanone and flavone aglycones as identified by liquid chromatography-high-resolution mass spectrometry...
April 26, 2018: Journal of Nutritional Biochemistry
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