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Hossein Sendi, Ivy Mead, Meimei Wan, Marjan Mehrab-Mohseni, Kenneth Koch, Anthony Atala, Herbert L Bonkovsky, Colin E Bishop
To investigate the role of miR-122 in the development and regression of non-alcoholic fatty liver disease (NAFLD) in vitro, we used multicellular 3D human liver organoids developed in our laboratory. These organoids consist of primary human hepatocytes, Kupffer cells, quiescent stellate cells and liver sinusoidal endothelial cells. They remain viable and functional for 4 weeks expressing typical markers of liver function such as synthesis of albumin, urea, and alpha-1 p450 drug metabolism. Before mixing, hepatic cells were transduced with lentivirus to inhibit miR122 expression (ABM, CA)...
2018: PloS One
Paulraj Kanmani, Hojun Kim
The beneficial effects of probiotics in several liver diseases have been investigated in both animal and clinical models; however, the precise mechanisms responsible for their effects have not yet been elucidated. Gut transmitted endotoxins such as LPS have been shown to play critical roles in hepatic inflammation and injury. Therefore, in this study, we investigated the beneficial role of selected lactic acid bacteria (LABs) on reduction of hepatic steatosis (HS) and attenuation of LPS induced inflammatory response in vitro ...
2018: Frontiers in Immunology
Constantine Melitas, Mick Meiselman
Obesity, insulin resistance, and metabolic syndrome continue to increase in prevalence. Hypertriglyceridemia is commonly associated and represents a valuable marker of metabolic syndrome. An increase in subcutaneous fat deposition places patients at risk for visceral adipose deposition in sites such as the liver, heart, and pancreas. Pancreatic steatosis in the setting of metabolic syndrome is a rapidly emerging entity whose clinical spectrum remains to be defined. Hypertriglyceridemia is an accepted cause of acute pancreatitis but its role in chronic pancreatic injury remains to be explored...
May 2018: Case Reports in Gastroenterology
Jane M Natividad, Bruno Lamas, Hang Phuong Pham, Marie-Laure Michel, Dominique Rainteau, Chantal Bridonneau, Gregory da Costa, Johan van Hylckama Vlieg, Bruno Sovran, Celia Chamignon, Julien Planchais, Mathias L Richard, Philippe Langella, Patrick Veiga, Harry Sokol
Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis is poorly understood. Here, we showed that B. wadsworthia synergizes with high fat diet (HFD) to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis. Host-microbiota transcriptomics analysis reveal pathways, particularly butanoate metabolism, which may underlie the metabolic effects mediated by B...
July 18, 2018: Nature Communications
Lorenzo Loffredo, Anna Maria Zicari, Ludovica Perri, Roberto Carnevale, Cristina Nocella, Francesco Angelico, Maria Del Ben, Antonella Mosca, Salvatore Zaffina, Nadia Panera, Anna Alisi, Marzia Duse, Francesco Violi, Valerio Nobili
It is unknown whether Nox2 activation is early associated with endotoxemia and liver damage in non-alcoholic fatty liver disease (NAFLD). To address this issue, we evaluated Nox2 activation, oxidative stress, gut permeability and lipolysaccharide (LPS) serum levels in 67 children with biopsy proven NAFLD and 73 controls. Compared to controls, NAFLD patients had higher Nox2 activity, isoprostanes, zonulin and LPS levels. Multivariate linear regression analysis showed that triglycerides, HDL, HOMA-IR, LPS and isoprostanes were independently associated with sNox2-dp levels...
July 18, 2018: Antioxidants & Redox Signaling
Daiane Gonçalves de Oliveira, Fabiana de Faria Ghetti, Ana Paula Boroni Moreira, Helen Hermana Miranda Hermsdorff, Juliano Machado de Oliveira, Lincoln Eduardo Villela Vieira de Castro Ferreira
PURPOSE: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, ballooning, and in some cases, fibrosis, which can progress to cirrhosis and carcinoma. The progression of NASH is closely related to oxidative stress. Dietary intake of antioxidants has been suggested in protection against oxidative damage and related clinical complications. Thus, we evaluated the potential association of dietary total antioxidant capacity (TAC) with disease severity in NASH patients, as well as with anthropometric and body composition markers and biochemical parameters...
July 17, 2018: European Journal of Nutrition
Mary Frances Lopez, Lingyun Zheng, Ji Miao, Reddy Gali, Grzegorz Gorski, Joel N Hirschhorn
Newborns with intrauterine growth-restriction are at increased risk of mortality and life-long co-morbidities. Insulin-like growth factor-II (IGF2) deficiency in humans as well as in mice leads to intrauterine growth restriction and decreased neonatal glycogen stores. The present study aims to further characterize the metabolic and transcriptional consequences of Igf2 deficiency in the newborn. We found that, despite being born significantly smaller than their wild-type (Igf2+/+ ) littermates, brain size was preserved in Igf2 knockout (Igf2-/- ), consistent with nutritional deficiency...
July 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Idalia Cura-Esquivel, Paula Cordero-Pérez, Liliana Torres-González, Linda E Muñoz-Espinosa
INTRODUCTION: Obesity is a worldwide public health problem and the most common non-communicable chronic disease. It is associated with an increase in inflammatory acute phase proteins and proinflammatory cytokines. OBJECTIVE: To assess the levels of acute phase proteins in obese children and adolescents with hepatic steatosis and metabolic syndrome. Methodology. Forty-five children with a body mass index ≥ 95th percentile aged 5.0-15.5 years were included. The following acute phase reactants were determined: C-reactive protein, haptoglobin, alpha-2-macroglobulin, and apolipoprotein A-1; besides, an ultrasound was done to assess hepatic steatosis...
August 1, 2018: Archivos Argentinos de Pediatría
Duan Li, Liwei Guo, Baoguo Deng, Min Li, Tingting Yang, Fan Yang, Zhijun Yang
Sterol regulatory element binding protein‑1c (SREBP‑1c), which serves an essential role in the process of fat synthesis, is a key adjustment factor that regulates the dynamic balance of lipid metabolism. SREBP‑1c activates the transcription of multiple genes encoding for enzymes involved in the synthesis of triglycerides (TG) and fatty acids (FA) and accelerates lipid synthesis. Previous analysis indicated that long non‑coding RNA HCV regulated 1 (lncHR1) participates in lipid metabolism in vivo and regulates the level of SREBP‑1c protein...
July 16, 2018: Molecular Medicine Reports
Yanli Wang, Peng Zhang, Xingli Su, Qi Yu, Yulong Chen, Hua Guan, Enqi Liu, Jianglin Fan
The aim of the present study was to establish a non‑alcoholic fatty liver disease (NAFLD) model using cholesterol‑fed rabbits and to investigate whether endoplasmic reticulum stress (ERS) serves a role in the pathogenesis of NAFLD. A total of 20 male rabbits were randomly divided into 3 groups: Those fed a normal chow diet, a high cholesterol diet (HCD) or a high fat and high cholesterol diet (HFCD) for 12 weeks. Total cholesterol, triglycerides and free fatty acids of plasma and the liver were measured...
July 6, 2018: Molecular Medicine Reports
Aeyung Kim, Jin Yeul Ma
Rhaponticin (RA; 3'5-dihydroxy-4'-methoxystilbene 3-O-β-D‑glucopyranoside) is a component isolated from various medicinal herbs including Rheum undulatum L. RA has been reported to be an effective treatment for allergy, diabetes, thrombosis, liver steatosis, lung fibrosis and colitis. In addition, RA effectively inhibits tumor growth and induces apoptosis; however, the effects of RA, at non-cytotoxic doses, on the metastasis and angiogenesis of malignant cancer cells have, to be the best of our knowledge, not been identified...
July 11, 2018: International Journal of Oncology
Li-Ping Han, Bei Sun, Chun-Jun Li, Yun Xie, Li-Ming Chen
Toll‑like receptor 4 (TLR4)‑mediated immune and inflammatory signaling serves a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Our previous study demonstrated that celastrol treatment was able to improve hepatic steatosis and inhibit the TLR4 signaling cascade pathway in type 2 diabetic rats. The present study aimed to investigate the effects of celastrol on triglyceride accumulation and inflammation in steatotic HepG2 cells, and the possible mechanisms responsible for the regulation of cellular responses following TLR4 gene knockdown by small interfering RNA (siRNA) in vitro...
July 12, 2018: International Journal of Molecular Medicine
Toshihiro Sakai, Hiroyuki Ohba, Shingo Nishiyama, Takeharu Kakiuchi, Osamu Inoue, Hideo Tsukada
BACKGROUND: Nonalcoholic fatty liver disease is a common disorder that progresses from simple fatty liver (steatosis) to nonalcoholic steatohepatitis (NASH). It is thought that mitochondrial dysfunction plays a critical role in the progression of NASH. In this study, we developed a non-invasive method for early diagnosis and staging of NASH that directly measures mitochondrial complex-I (MC-I) activity in the liver of NASH model mice by positron emission tomography (PET) imaging using the novel tracer 2-tert-butyl-4-chloro-5-[6-(4-[18 F]fluorobutoxy)-pyridin-3-ylmethoxy]-2H-pyridazin-3-one (18 F-BCPP-BF)...
July 16, 2018: EJNMMI Research
Ahad Eshraghian, Shahrokh Iravani, Pedram Azimzadeh
BACKGROUND Genetic predisposition may have important role in pathogenesis of non-alcoholic fatty liver disease (NAFLD). Angiotensin II type I receptor (AGTR1) has been known to involve in the process of liver steatosis and fibrosis. This study aimed to investigate the association between AGTR1 A1166C polymorphism and NAFLD. METHODS A cross-sectional study was conducted during May 2014-May 2015 among healthy adults referring to our radiology clinic for abdominal sonography. AGTR1 A1166C polymorphism was evaluated in subjects with NAFLD and healthy individuals using allelic discrimination method...
April 2018: Middle East Journal of Digestive Diseases
Seyed Reza Modares Mousavi, Bita Geramizadeh, Amir Anushiravani, Fardad Ejtehadi, Mohammad Hossein Anbardar, Maryam Moini
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Recently several parameters, such as serum ferritin, have emerged as possible predictors for the severity of NAFLD and insulin sensitivity. We aimed to investigate the value of serum ferritin level as a useful biomarker for the prediction of histopathological disease severity in non-alcoholic steatohepatitis (NASH), the necro-inflammatory form of NAFLD. METHODS This was a prospective cross sectional study in which demographic, clinical, histological, laboratory, and anthropometric data of 30 adult patients with biopsy-proven NAFLD/NASH were analyzed...
April 2018: Middle East Journal of Digestive Diseases
Won-Gyeong Kim, Hye In Kim, Eun Kyung Kwon, Myung Joo Han, Dong-Hyun Kim
Long-term exposure to ethanol simultaneously causes gastrointestinal inflammation, liver injury, and steatosis. In the present study, we investigated the effects of Bifidobacterium longum LC67, Lactobacillus plantarum LC27, and their mixture (LM) against ethanol-induced steatosis in mice. Exposure to ethanol caused liver damage: it increased ALT, AST, TG, TC, and lipopolysaccharide levels in the blood and induced NF-κB activation in the liver. Oral administration of LC27, LC67, or LM in mice reduced ethanol-induced ALT, AST, TG, and TC levels in the blood and liver...
July 16, 2018: Food & Function
Ghada Abdelmoemen, Samy Abdelkader Khodeir, Ahmed Nabil Zaki, Maha Kassab, Sabry Abou-Saif, Sherief Abd-Elsalam
BACKGROUND & AIMS: Insulin resistance is the real determinant of both Nonalcoholic fatty liver disease (NAFLD) and diabetes, and can facilitate the accumulation of triglycerides in the liver. Overexpression of hepassocin (HPS) increased the accumulation of hepatic fat and NAFLD activity scores (NAS) in mice. The aim of this study was to investigate the relationship between hepassocin and steatosis of the liver in diabetic patients with or without NAFLD in humans. METHODS: The study enrolled 60 patients plus 20 healthy controls that were divided into 4 groups: Group I: included 20 patients who were diagnosed as diabetes mellitus type 2, Group II: included 20 patients who were diagnosed as nonalcoholic fatty liver disease (NAFLD), Group III: included 20 patients who were diagnosed as diabetes type 2 and NAFLD, and Group IV (control group): included 20 healthy person or controls who were matched in age and sex with patients group...
July 15, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
Rory P Cunningham, Mary P Moore, Angelique N Moore, James C Healy, Michael D Roberts, R Scott Rector, Jeffrey S Martin
Curcumin, a naturally occurring plant polyphenolic compound, may have beneficial effects in nonalcoholic steatohepatitis (NASH) development. We examined whether curcumin supplementation could be used in both prevention and treatment of NASH with fibrosis. Female Wistar rats were provided ad libitum access to a "western diet" (WD) high in fat (43% kcal), sucrose (29% kcal), and cholesterol (2% w/v), as well as 15% fructose drinking water. Intraperitoneal CC14 injections (0.5 mL/kg) were also administered at weeks 1, 2, 4, and 6 to accelerate development of a NASH with fibrosis phenotype...
July 2018: Physiological Reports
Sherif Mohamed Zaki, Shereen Abdel Fattah, Dina Salah Hassan
BACKGROUND: The western-style diet is characterized by the high intake of energy-dense foods. Consumption of either high fructose diet or saturated fat resulted in the development of metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Many researchers studied the effect of high-fat diet (HFD), high fructose diet (HFruD) and high fructose high-fat diet (HFHF) on the liver. The missing data are the comparison effect of these groups i...
July 16, 2018: Folia Morphologica (Warsz)
Sorim Choung, Kyong Hye Joung, Bo Ram You, Sang Ki Park, Hyun Jin Kim, Bon Jeong Ku
Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. The peroxisome proliferator-activated receptor (PPAR) activators, thiazolidinediones, (TZDs), are insulin sensitizers used as a treatment for NAFLD. However, TZDs are a controversial treatment for NAFLD because of conflicting results regarding hepatic steatosis and fibrosis. To evaluate a possible effective drug for treatment of NAFLD, we investigated the effects of a newly developed TZD, lobeglitazone, with an emphasis on hepatic lipid metabolism...
2018: PPAR Research
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