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Choline AND Triglycerides

Franz Josef Söbbeler, Inés Carrera, Kirby Pasloske, Millagahamada Gedara Ranasinghe, Patrick Kircher, Sabine Beate Rita Kästner
BACKGROUND: The purpose of this study was to determine the effects of isoflurane, sevoflurane, propofol and alfaxalone on the canine brain metabolite bioprofile, measured with single voxel short echo time proton magnetic resonance spectroscopy at 3 Tesla. Ten adult healthy Beagle dogs were assigned to receive isoflurane, sevoflurane, propofol and alfaxalone at 3 different dose rates each in a randomized cross-over study design. Doses for isoflurane, sevoflurane, propofol and alfaxalone were FE 'Iso 1...
March 5, 2018: BMC Veterinary Research
Hui Liang, Yutong Wang
Abnormal lipid metabolism may contribute to the pathogenesis of non-alcoholic steatohepatitis (NASH). The ATP-binding cassette transporter A1 (ABCA1) protein mediates the transport of cholesterol and phospholipids from cells to apolipoprotein A-I (apoA-I) to generate nascent HDL particles. Previous studies revealed that the overexpression of ABCA1 alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effect of berberine (BBR) on ABCA1 in QSG-7701 hepatocytes and in mice. BBR decreased hepatic cholesterol and triglyceride levels...
March 2, 2018: Biochemical and Biophysical Research Communications
Yuichiro Amano, Shuntarou Tsuchiya, Mayumi Imai, Kimio Tohyama, Jun Matsukawa, Osamu Isono, Hironobu Yasuno, Kazuaki Enya, Emiko Koumura, Hiroshi Nagabukuro
This study aimed to evaluate the effects of combination therapy with a dipeptidyl peptidase-4 inhibitor, alogliptin, and a peroxisome proliferator-activated receptor-γ agonist, pioglitazone, in a preclinical model of nonalcoholic steatohepatitis using low-density lipoprotein receptor-knockout mice fed a modified choline-deficient l-amino acid-defined diet. Monotherapy with either alogliptin (10-200 mg/kg) or pioglitazone (6-20 mg/kg) significantly decreased hepatic triglyceride content and fibrosis. The concomitant treatment of alogliptin (30 mg/kg), pioglitazone (20 mg/kg) also decreased hepatic triglyceride and hepatic collagen-I mRNA at greater extent compared to monotherapy...
February 8, 2018: Biochemical and Biophysical Research Communications
Guillaume Wettstein, Jean-Michel Luccarini, Laurence Poekes, Patrick Faye, Francine Kupkowski, Vanessa Adarbes, Evelyne Defrêne, Céline Estivalet, Xavier Gawronski, Ingrid Jantzen, Alain Philippot, Julien Tessier, Pascale Tuyaa-Boustugue, Fiona Oakley, Derek A Mann, Isabelle Leclercq, Sven Francque, Irena Konstantinova, Pierre Broqua, Jean-Louis Junien
IVA337 is a pan-peroxisome proliferator-activated receptor (PPAR) agonist with moderate and well-balanced activity on the three PPAR isoforms (α, γ, δ). PPARs are regulators of lipid metabolism, inflammation, insulin resistance, and fibrogenesis. Different single or dual PPAR agonists have been investigated for their therapeutic potential in nonalcoholic steatohepatitis (NASH), a chronic liver condition in which steatosis coexists with necroinflammation, potentially leading to liver fibrosis and cirrhosis...
August 2017: Hepatology communications
Jin-Sung Park, Young-Jun Shim, Byeong-Ho Kang, Woon-Kyu Lee, Bon-Hong Min
Clusterin is a multifunctional glycoprotein that plays important roles and is up-regulated in liver diseases such as hepatitis and hepatocellular carcinoma. However, little is known about the significance of clusterin in the pathogenesis of non-alcoholic steatohepatitis (NASH). The aim of this study is to examine the role of clusterin in progression of steatohepatitis in mice fed a methionine and choline deficient (MCD) diet. We generated hepatocyte-specific clusterin overexpression (hCLU-tg) mice, and hCLU-tg mice showed lower levels of hepatic triglycerides, less infiltration of macrophages and reduction of TNF-α, activation of Nrf-2 than wild-type littermates fed the MCD diet...
January 8, 2018: Biochemical and Biophysical Research Communications
Bittu Saira Koshy, Jaideep Mahendra
Introduction: Lipoprotein associated phospholipase A2 (Lp-PLA2) has been explored as a potential biomarker for Cardiovascular Disease (CVD). The human Lp-PLA2 is a serine-dependent, Ca2+- independent enzyme. It gives way to oxidised free fatty acids and lysophosphatidyl choline by hydrolysing oxidised phospholipids, that leads to smooth muscle cell apoptosis, inflammatory cell chemotaxis and endothelial cell dysfunction in CVD. Owing to its role in inflammation, it may influence the development and progression of periodontitis as well...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
Marta Iruarrizaga-Lejarreta, Marta Varela-Rey, David Fernández-Ramos, Ibon Martínez-Arranz, Teresa C Delgado, Jorge Simon, Virginia Gutiérrez-de Juan, Laura delaCruz-Villar, Mikel Azkargorta, José L Lavin, Rebeca Mayo, Sebastiaan M Van Liempd, Igor Aurrekoetxea, Xabier Buqué, Donatella Delle Cave, Arantza Peña, Juan Rodríguez-Cuesta, Ana M Aransay, Felix Elortza, Juan M Falcón-Pérez, Patricia Aspichueta, Liat Hayardeny, Mazen Noureddin, Arun J Sanyal, Cristina Alonso, Juan Anguita, María Luz Martínez-Chantar, Shelly C Lu, José M Mato
Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease (NAFLD) which sets the stage for further liver damage. The mechanism for the progression of NASH involves multiple parallel hits including oxidative stress, mitochondrial dysfunction, inflammation and others. Manipulation of any of these pathways may be an approach to prevent NASH development and progression. Aramchol (arachidyl-amido cholanoic acid) is presently in a phase IIb NASH study. The aim of this study was to investigate Aramchol's mechanism of action and its effect on fibrosis using the methionine- and choline-deficient (MCD) diet model of NASH...
November 2017: Hepatology Communications
Ming Zhang, Yujie Zhao, Zhen Li, Congying Wang
Nonalcoholic steatohepatitis (NASH) is a progressive disease and poses a high risk of severe liver damage. However, the pathogenesis of NASH is still unclear. Accumulation of lipid droplets and insulin resistance is the hallmark of NASH. Pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) plays key role in glucose metabolism via regulating the activity of pyruvate dehydrogenase complex (PDC). Here, we demonstrated a novel of PDK4 in NASH by regulating hepatic steatosis and insulin signaling pathway in methionine and choline deficient (MCD) diet induced NASH model...
November 8, 2017: Biochemical and Biophysical Research Communications
Águeda González-Rodríguez, M Pilar Valdecantos, Patricia Rada, Annalisa Addante, Inés Barahona, Esther Rey, Virginia Pardo, Laura Ruiz, Laura M Laiglesia, María J Moreno-Aliaga, Carmelo García-Monzón, Aránzazu Sánchez, Ángela M Valverde
OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries. Protein tyrosine phosphatase 1B (PTP1B), a negative modulator of insulin and cytokine signaling, is a therapeutic target for type 2 diabetes and obesity. We investigated the impact of PTP1B deficiency during NAFLD, particularly in non-alcoholic steatohepatitis (NASH). METHODS: NASH features were evaluated in livers from wild-type (PTP1BWT) and PTP1B-deficient (PTP1BKO) mice fed methionine/choline-deficient diet (MCD) for 8 weeks...
October 31, 2017: Molecular Metabolism
Melanie Tran, Sang-Min Lee, Dong-Ju Shin, Li Wang
Accumulation of lipid droplets and inflammatory cell infiltration is the hallmark of nonalcoholic steatohepatitis (NASH). The roles of noncoding RNAs in NASH are less known. We aim to elucidate the function of miR-141/200c in diet-induced NASH. WT and miR-141/200c-/- mice were fed a methionine and choline deficient (MCD) diet for 2 weeks to assess markers of steatosis, liver injury, and inflammation. Hepatic miR-141 and miR-200c RNA levels were highly induced in human patients with NASH fatty liver and in WT MCD mice...
November 2, 2017: JCI Insight
Lotte Geys, Elien Roose, Karen Vanhoorelbeke, Pierre Bedossa, Ilse Scroyen, H Roger Lijnen
Previous studies, predominantly based on increased or decreased plasma levels, have reported conflicting data on a potential functional role of ADAMTS13 in the pathogenesis of liver diseases, including non‑alcoholic steatohepatitis (NASH). The aim of the current study was to evaluate whether ADAMTS13 deficiency affects development of NASH. Therefore, male wild‑type (WT) and Adamts13 deficient (Adamts13‑/‑) mice were kept on a steatosis‑inducing diet devoid of methionine and choline (MCD) or a control diet (MCC) for 4 weeks...
August 2017: Molecular Medicine Reports
Mi Ra Lee, Jin Yeul Ma, Chang Keun Sung
BACKGROUND: Black ginseng has a more potent biological activity than non-steamed ginseng. We investigated the effects of long-term intake of dietary black ginseng extract (BG) on antioxidant activity in aged mice. We also compared the effects of BG on cognitive deficits with those of white ginseng extract (WG) and red ginseng extract (RG). METHODS: Ten-month-old mice were fed an AIN-93G-based diet containing 10 g/kg (low dose, L) or 30 g/kg (high dose, H) WG powder, RG powder, or BG powder for 24 wk...
October 2017: Journal of Ginseng Research
Bradford D Bagley, Shu-Ching Chang, David J Ehresman, Alan Eveland, Jeremiah D Zitzow, George A Parker, Jeffrey M Peters, Kendall B Wallace, John L Butenhoff
Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100 ppm PFOS fed to male mice and rats for 4 weeks caused hepatic steatosis through an unknown mechanism. Choline deficient diets can cause hepatic steatosis. A hepatic choline:PFOS ion complex was hypothesized to cause this effect in mice. This study tested whether dietary choline supplementation attenuates PFOS-induced hepatic steatosis in rats. Sprague Dawley rats (12/sex/group) were fed control, choline supplemented (CS), 100 ppm PFOS, or 100 ppm PFOS + CS diets for 3 weeks...
December 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
Andrew A Pierce, Caroline C Duwaerts, Kevin Siao, Aras N Mattis, Amanda Goodsell, Jody L Baron, Jacquelyn J Maher
Neutrophils and macrophages are important constituents of the hepatic inflammatory infiltrate in non-alcoholic steatohepatitis. These innate immune cells express CD18, an adhesion molecule that facilitates leukocyte activation. In the context of fatty liver, activation of infiltrated leukocytes is believed to enhance hepatocellular injury. The objective of this study was to determine the degree to which activated innate immune cells promote steatohepatitis by comparing hepatic outcomes in wild-type and CD18-mutant mice fed a methionine-choline-deficient (MCD) diet...
2017: PloS One
James Kinross, Reza Mirnezami, James Alexander, Richard Brown, Alasdair Scott, Dieter Galea, Kirill Veselkov, Rob Goldin, Ara Darzi, Jeremy Nicholson, Julian R Marchesi
Colon cancer induces a state of mucosal dysbiosis with associated niche specific changes in the gut microbiota. However, the key metabolic functions of these bacteria remain unclear. We performed a prospective observational study in patients undergoing elective surgery for colon cancer without mechanical bowel preparation (n = 18). Using 16 S rRNA gene sequencing we demonstrated that microbiota ecology appears to be cancer stage-specific and strongly associated with histological features of poor prognosis...
August 21, 2017: Scientific Reports
Chauntelle Jack-Roberts, Yaelle Joselit, Khatia Nanobashvili, Rachel Bretter, Olga V Malysheva, Marie A Caudill, Anjana Saxena, Kathleen Axen, Ahmed Gomaa, Xinyin Jiang
Maternal obesity increases fetal adiposity which may adversely affect metabolic health of the offspring. Choline regulates lipid metabolism and thus may influence adiposity. This study investigates the effect of maternal choline supplementation on fetal adiposity in a mouse model of maternal obesity. C57BL/6J mice were fed either a high-fat (HF) diet or a control (NF) diet and received either 25 mM choline supplemented (CS) or control untreated (CO) drinking water for 6 weeks before timed-mating and throughout gestation...
August 18, 2017: Nutrients
Jing-Hui Sun, Xu Liu, Li-Xin Cong, He Li, Cheng-Yi Zhang, Jian-Guang Chen, Chun-Mei Wang
BACKGROUND: Schisandra, a globally distributed plant, has been widely applied for the treatment of diseases such as hyperlipidemia, fatty liver and obesity in China. In the present work, a rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS)-based metabolomics was conducted to investigate the intervention effect of Schisandra chinensis lignans (SCL) on hyperlipidemia mice induced by high-fat diet (HFD). METHODS: Hyperlipidemia mice were orally administered with SCL (100 mg/kg) once a day for 4 weeks...
August 1, 2017: Lipids in Health and Disease
Sou Hyun Kim, Yong Lim, Ju Bin Park, Jae-Hwan Kwak, Keuk-Jun Kim, Joung-Hee Kim, HyunKeun Song, Joon Young Cho, Dae Youn Hwang, Kil Soo Kim, Young-Suk Jung
Non-alcoholic fatty liver disease (NAFLD) is believed to be the most prevalent liver disease worldwide and a major cause of chronic liver injury. It is characterized by lipid accumulation in the absence of significant alcohol consumption and frequently progresses to steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Although many studies have been conducted to better understand NAFLD since it was first recognized, there are still many gaps in knowledge of etiology, prognosis, prevention and treatment...
June 2017: Laboratory Animal Research
Pierluigi Ramadori, Hannah Drescher, Stephanie Erschfeld, Athanassios Fragoulis, Thomas W Kensler, Christoph Jan Wruck, Francisco Javier Cubero, Christian Trautwein, Konrad L Streetz, Daniela C Kroy
We have recently shown that hepatocyte-specific c-met deficiency accelerates the progression of nonalcoholic steatohepatitis in experimental murine models resulting in augmented production of reactive oxygen species and accelerated development of fibrosis. The aim of this study focuses on the elucidation of the underlying cellular mechanisms driven by Nrf2 overactivation in hepatocytes lacking c-met receptor characterized by a severe unbalance between pro-oxidant and antioxidant functions. Control mice (c-met(fx/fx)), single c-met knockouts (c-met(Δhepa)), and double c-met/Keap1 knockouts (met/Keap1(Δhepa)) were then fed a chow or a methionine-choline-deficient (MCD) diet, respectively, for 4 weeks to reproduce the features of nonalcoholic steatohepatitis...
2017: Oxidative Medicine and Cellular Longevity
Liene Bervoets, Guy Massa, Wanda Guedens, Evelyne Louis, Jean-Paul Noben, Peter Adriaensens
BACKGROUND: Type 1 diabetes mellitus (T1DM) is one of the most common pediatric diseases and its incidence is rising in many countries. Recently, it has been shown that metabolites other than glucose play an important role in insulin deficiency and the development of diabetes. The aim of our study was to look for discriminating variation in the concentrations of small-molecule metabolites in the plasma of T1DM children as compared to non-diabetic matched controls using proton nuclear magnetic resonance ((1)H-NMR)-based metabolomics...
2017: Diabetology & Metabolic Syndrome
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