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https://www.readbyqxmd.com/read/29128353/pyruvate-dehydrogenase-kinase-4-mediates-lipogenesis-and-contributes-to-the-pathogenesis-of-nonalcoholic-steatohepatitis
#1
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
https://www.readbyqxmd.com/read/29126873/dual-role-of-protein-tyrosine-phosphatase-1b-in-the-progression-and-reversion-of-non-alcoholic-steatohepatitis
#2
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
https://www.readbyqxmd.com/read/29093267/loss-of-mir-141-200c-ameliorates-hepatic-steatosis-and-inflammation-by-reprogramming-multiple-signaling-pathways-in-nash
#3
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
https://www.readbyqxmd.com/read/29067443/role-of-adamts13-in-diet-induced-liver-steatosis
#4
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
https://www.readbyqxmd.com/read/29021712/chronic-dietary-ginseng-extract-administration-ameliorates-antioxidant-and-cholinergic-systems-in-the-brains-of-aged-mice
#5
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
https://www.readbyqxmd.com/read/28973659/perfluorooctane-sulfonate-induced-hepatic-steatosis-in-male-sprague-dawley-rats-is-not-attenuated-by-dietary-choline-supplementation
#6
Bradford D Bagley, Shu-Ching Chang, David J Ehresman, Alan Eveland, Jeremiah 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 four 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 three weeks...
August 30, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28873429/cd18-deficiency-improves-liver-injury-in-the-mcd-model-of-steatohepatitis
#7
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
https://www.readbyqxmd.com/read/28827587/a-prospective-analysis-of-mucosal-microbiome-metabonome-interactions-in-colorectal-cancer-using-a-combined-mas-1hnmr-and-metataxonomic-strategy
#8
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
https://www.readbyqxmd.com/read/28820499/choline-supplementation-normalizes-fetal-adiposity-and-reduces-lipogenic-gene-expression-in-a-mouse-model-of-maternal-obesity
#9
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
https://www.readbyqxmd.com/read/28764799/metabolomics-study-of-the-therapeutic-mechanism-of-schisandra-chinensis-lignans-in-diet-induced-hyperlipidemia-mice
#10
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
https://www.readbyqxmd.com/read/28747982/comparative-study-of-fatty-liver-induced-by-methionine-and-choline-deficiency-in-c57bl-6n-mice-originating-from-three-different-sources
#11
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
https://www.readbyqxmd.com/read/28676836/genetic-nrf2-overactivation-inhibits-the-deleterious-effects-induced-by-hepatocyte-specific-c-met-deletion-during-the-progression-of-nash
#12
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
https://www.readbyqxmd.com/read/28674557/metabolic-profiling-of-type-1-diabetes-mellitus-in-children-and-adolescents-a-case-control-study
#13
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
https://www.readbyqxmd.com/read/28638995/transport-of-long-chain-polyunsaturated-fatty-acids-in-preterm-infant-plasma-is-dominated-by-phosphatidylcholine
#14
Wolfgang Bernhard, Christoph Maas, Anna Shunova, Michaela Mathes, Katrin Böckmann, Christine Bleeker, Julia Vek, Christian F Poets, Erwin Schleicher, Axel R Franz
BACKGROUND: Docosahexaenoic (C22:6) and arachidonic (C20:4) acids are long-chain polyunsaturated fatty acids (LC-PUFA) essential to neonatal development, being present in the glycerophospholipids of all organs, particularly the brain. In plasma, LC-PUFAs are mainly present in lipoprotein lipids, which are neutral lipids (triglycerides and cholesterol esters) and glycerophospholipids, like choline containing phosphatidylcholine (PC). PURPOSE: To guide future supplementation strategies of C22:6 and C20:4 in combination with choline, we determined the distribution of C20:4 and C22:6 between PC and neutral lipid...
June 20, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28615649/andrographolide-ameliorates-inflammation-and-fibrogenesis-and-attenuates-inflammasome-activation-in-experimental-non-alcoholic-steatohepatitis
#15
Daniel Cabrera, Alexander Wree, Davide Povero, Nancy Solís, Alejandra Hernandez, Margarita Pizarro, Han Moshage, Javiera Torres, Ariel E Feldstein, Claudio Cabello-Verrugio, Enrique Brandan, Francisco Barrera, Juan Pablo Arab, Marco Arrese
Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-κB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the effects of ANDRO in NASH and its influence on inflammasome activation in this setting. Thus, mice were fed a choline-deficient-amino-acid-defined (CDAA) diet with/without concomitant ANDRO administration (1 mg/kg, 3-times/week)...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28497207/evaluation-of-rumen-protected-choline-additive-to-diet-on-productive-performance-of-male-zaraibi-growing-goats-during-hot-summer-season-in-egypt
#16
A A M Habeeb, A E Gad, M A A Atta, M A M Abdel-Hafez
Twenty Zaraibi goat bucks were used in this experiment which lasted 3 months during summer season of Egypt. The animals were divided randomly into two equal groups. The first group was kept without treatment as control while in the second group, rumen-protected choline (RPC) at the level of 20 g/buck/day was added to the concentrate feed mixture at the morning feeding. RPC additives to diet of Zaraibi goat bucks during the period of hot summer season increased (P < 0.01) total gain and average daily gain compared to the control group...
August 2017: Tropical Animal Health and Production
https://www.readbyqxmd.com/read/28447460/effects-of-histidine-supplementation-on-global-serum-and-urine-1-h-nmr-based-metabolomics-and-serum-amino-acid-profiles-in-obese-women-from-a-randomized-controlled-study
#17
Shanshan Du, Shuhong Sun, Liyan Liu, Qiao Zhang, Fuchuan Guo, Chunlong Li, Rennan Feng, Changhao Sun
The aim of current study was to investigate the metabolic changes associated with histidine supplementation in serum and urine metabolic signatures and serum amino acid (AA) profiles. Serum and urine (1)H NMR-based metabolomics and serum AA profiles were employed in 32 and 37 obese women with metabolic syndrome (MetS) intervened with placebo or histidine for 12 weeks. Multivariable statistical analysis were conducted to define characteristic metabolites. In serum (1)H NMR metabolic profiles, increases in histidine, glutamine, aspartate, glycine, choline, and trimethylamine-N-oxide (TMAO) were observed; meanwhile, decreases in cholesterol, triglycerides, fatty acids and unsaturated lipids, acetone, and α/β-glucose were exhibited after histidine supplement...
June 2, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28428116/cycloastragenol-improves-hepatic-steatosis-by-activating-farnesoid-x-receptor-signalling
#18
Ming Gu, Shiying Zhang, Yuanyuan Zhao, Jinwen Huang, Yahui Wang, Yin Li, Shengjie Fan, Li Yang, Guang Ji, Qingchun Tong, Cheng Huang
Non-alcoholic fatty liver disease (NAFLD) has become a global health problem. However, there is no approved therapy for NAFLD. Farnesoid X receptor (FXR) is a potential drug target for treatment of NAFLD. In an attempt to screen FXR agonists, we found that cycloastragenol (CAG), a natural occurring compound in Astragali Radix, stimulated FXR transcription activity. In animal studies, we demonstrated that CAG treatment resulted in obvious reduction of high-fat diet induced lipid accumulation in liver accompanied by lowered blood glucose, serum triglyceride levels and hepatic bile acid pool size...
April 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28396286/altered-mitochondrial-and-peroxisomal-integrity-in-lipocalin-2-deficient-mice-with-hepatic-steatosis
#19
Anastasia Asimakopoulou, Annabelle Fülöp, Erawan Borkham-Kamphorst, Eddy Van de Leur, Nikolaus Gassler, Thorsten Berger, Birte Beine, Helmut E Meyer, Tak W Mak, Carsten Hopf, Corinna Henkel, Ralf Weiskirchen
Lipocalin-2 (LCN2) is a secreted adipokine that transports small hydrophobic molecules such as fatty acids and steroids. LCN2 limits bacterial growth by sequestering iron-containing siderophores and in mammalian liver protects against inflammation, infection, injury and other stressors. Because LCN2 modulates hepatic fat metabolism and homeostasis, we performed a comparative profiling of proteins and lipids of wild type (WT) and Lcn2-deficient mice fed either standard chow or a methionine- and choline-deficient (MCD) diet...
April 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28356272/choline-and-its-metabolites-are-differently-associated-with-cardiometabolic-risk-factors-history-of-cardiovascular-disease-and-mri-documented-cerebrovascular-disease-in-older-adults
#20
Annie J Roe, Shucha Zhang, Rafeeque A Bhadelia, Elizabeth J Johnson, Alice H Lichtenstein, Gail T Rogers, Irwin H Rosenberg, Caren E Smith, Steven H Zeisel, Tammy M Scott
Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism.Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovascular disease, and cerebrovascular pathology.Design: A cross-sectional subset of the Nutrition, Aging, and Memory in Elders cohort who had undergone MRI of the brain (n = 296; mean ± SD age: 73 ± 8.1 y) was assessed...
June 2017: American Journal of Clinical Nutrition
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