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| 1 | Metabolic and hepatic effects of liraglutide,obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis(NASH) in obese mouse models of biopsy-confirmedNASH.METHODS Male wild-type C57 BL/6 J mice(DIO-NASH) and Lep^(ob/ob)(ob/ob-NASH) mice were fed a diet high in trans-fat(40%), fructose(20%) and cholesterol(2%) for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis, using the nonalcoholic fatty liver disease activity score(NAS) and fibrosis staging system. The mice were kept on the diet and received vehicle, liraglutide(0.2 mg/kg, SC, BID), obeticholic acid(OCA, 30 mg/kg PO, QD), or elafibranor(30 mg/kg PO, QD) for eight weeks. Within-subject comparisons were performed on changes in steatosis, inflammation, ballooning degeneration, and fibrosis scores. In addition, compound effects were evaluated by quantitative liver histology, including percent fractional area of liver fat, galectin-3, and collagen 1 a1.RESULTS Liraglutide and elafibranor, but not OCA, reduced body weight in both models. Liraglutide improved steatosis scores in DIO-NASH mice only. Elafibranor and OCA reduced histopathological scores of hepatic steatosis and inflammation in both models, but only elafibranor reduced fibrosis severity. Liraglutide and OCA reduced total liver fat, collagen 1 a1, and galectin-3 content, driven by significant reductions in liver weight. The individual drug effects on NASH histological endpoints were supported by global gene expression(RNA sequencing) and liver lipid biochemistry.CONCLUSION DIO-NASH and ob/ob-NASH mouse models show distinct treatment effects of liraglutide, OCA, and elafibranor, being in general agreement with corresponding findings in clinical trials for NASH. The present data therefore further supports the clinical translatability and utility of DIO-NASH and ob/ob-NASH mouse models of NASH for probing the therapeutic efficacy of compounds in preclinical drug development for NASH. | Kirstine S Tolbol Maria NB Kristiansen Henrik H Hansen Sanne S Veidal Kristoffer TG Rigbolt Matthew P Gillum Jacob Jelsing Niels Vrang Michael Feigh | 2018 | World Journal of Gastroenterology2018，24，2： | 5 |
| 2 | Ropivacaine:a pharmacological review显示文摘 | Hansen TG | 2004 | Expert Rev Neurother2004，4，5： | 1 |
| 3 | Caudal bupivacaine supplemented with caudal or intravenous clonidine in children undergoing hypospadias repair : a double - blind study 显示文摘 | Hansen TG Henneberg SW Walther LS | 2004 | British Journal of Anaesthesia2004，92，2： | 1 |
| 4 | Academic per- formance in adolescence after inguinal hernia repair in infancy: a nationwide cohort study 显示文摘 | Hansen TG Pedersen JK Henneberg SW | 2011 | Anesthesiology2011，114，5： | 1 |
| 5 | Ropivacaine:a pharmacological review显示文摘 | Hansen TG | | 0，，05： | 1 |
| 6 | Biophysical charac- terization of the new human ether-a-go-go-related gene channel o- pener NS3623显示文摘 | HANSEN RS DINESS TG CHRIST T | 2006 | Mol Pharmacol2006，70，4： | 1 |
| 7 | Academic performance in adolescence after inguinal hernia repair in infancy : a nationwide cohort study 显示文摘 | Hansen TG Pedersen JK Henneberg SW | 2011 | Anesthesiology2011，114，5： | 1 |
| 8 | Academic performance in adolescence after inguinal hernia repair in infancy:a nationwide cohort study显示文摘 | Hansen TG | 2011 | Anesthesiology2011，114，5： | 1 |
| 9 | Differences between anterior and posterior circulation stroke in TOAST 显示文摘 | Libman RB Kwiatkowski TG Hansen MD | 2001 | Cerebrovasc Dis2001，11，4： | 1 |
| 10 | Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children显示文摘 | Hansen TG | 2015 | Paediatr Anaesth2015，25，1： | 1 |
| 11 | Ropivacaine:a pharmacological review显示文摘 | | 2004 | Expert Rev Neurother2004，4，5： | 1 |
| 12 | Academic performance in adolescence after inguinal hernia repair in infancy:a nationwide cohort study显示文摘 | Hansen TG Pedersen JK Henneberg SW | | 0，，： | 1 |
| 13 | Levetiracetam prevents changes in levels of brain-derived neurotrophic factor and neuropeptide Y mRNA and of Y1 - and Y5-like receptors in the hippocampus of rats undergoing amygdala kindling: implications for antiepileptogenic and mood-stabilizing properties显示文摘 | Husum H Bolwig TG Sanchez C Mathe AA Hansen SL | 2004 | Epilepsy Behav2004，5，1： | 1 |
| 14 | Intensity modulated radiotherapy (IMRT) in locally advanced thyroid cancer: acute toxicity results of a phase I study显示文摘 | Urbano TG Clark CH Hansen VN | 2007 | Radiother Oncol2007，85，1： | 1 |
| 15 | The peri-operative cytokine response in infants and yang children following major surgery显示文摘 | Hansen TG Tonnesen E Andersen JB | 1998 | Eur J Anaesthesiol1998，15，： | 1 |
| 16 | Plasma paracetamol concentrations and pharmacokinetics following rectal administration in neonates and young infants显示文摘 | Hansen TG Brien K Morton NS | 1999 | Acta Anaesthesiol Scand1999，43，8： | 1 |
| 17 | Ropivacaine: a pharmacological review 显示文摘 | Hansen TG | 2004 | Expert Rev Neurother2004，4，5： | 1 |
| 18 | The peri-operative cytokine response in infants and yang children following major surgery显示文摘 | Hansen TG Tonnesen E Andersen JB | 1998 | Eur J Anaesthesiol1998，15，： | 1 |
| 19 | Academic performance in adolescence after inguinal hernia repair in infancy: a nationwide cohort study显示文摘 | Hansen TG Pedersen JK Henneberg SW | 2011 | Anesthesiology2011，114，5： | 1 |
| 20 | The impact of receiving an HIV diagnosis and cognitive processing on psychological distress and post- traumatic growth显示文摘 | Nightingale VR Sher TG Hansen NB | 2010 | J Trauma Stress2010，23，4： | 1 |
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