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| 1 | Nonalcoholic steatohepatitis severity is defined by a failure in compensatory antioxidant capacity in the setting of mitochondrial dysfunction显示文摘AIM To comprehensively evaluate mitochondrial(dys) function in preclinical models of nonalcoholic steatohepatitis(NASH).METHODS We utilized two readily available mouse models of nonalcoholic fatty liver disease(NAFLD) with or without progressive fibrosis: Lep^(ob)/Lep^(ob)(ob/ob) and FATZO mice on high trans-fat, high fructose and high cholesterol(AMLN) diet. Presence of NASH was assessed using immunohistochemical and pathological techniques, and gene expression profiling. Morphological features of mitochondria were assessed via transmission electron microscopy and immunofluorescence, and function was assessed by measuring oxidative capacity in primary hepatocytes, and respiratory control and proton leak in isolated mitochondria. Oxidative stress was measured by assessing activity and/or expression levels of Nrf1, Sod1, Sod2, catalase and 8-OHdG. RESULTS When challenged with AMLN diet for 12 wk, ob/ob and FATZO mice developed steatohepatitis in the presence of obesity and hyperinsulinemia. NASH development was associated with hepatic mitochondrial abnormalities, similar to those previously observed in humans, including mitochondrial accumulation and increased proton leak. AMLN diet also resulted in increased numbers of fragmented mitochondria in both strains of mice. Despite similar mitochondrial phenotypes, we found that ob/ob mice developed more advanced hepatic fibrosis. Activity of superoxide dismutase(SOD) was increased in ob/ob AMLN mice, whereas FATZO mice displayed increased catalase activity, irrespective of diet. Furthermore, 8-OHd G, a marker of oxidative DNA damage, was significantly increased in ob/ob AMLN mice compared to FATZO AMLN mice. Therefore, antioxidant capacity reflected as the ratio of catalase:SOD activity was similar between FATZO and C57 BL6 J control mice, but significantly perturbed in ob/ob mice. CONCLUSION Oxidative stress, and/or the capacity to compensate for increased oxidative stress, in the setting of mitochondrial dysfunction, is a key factor for development of hepatic injury and fibrosis in these mouse models. | Michelle L Boland Stephanie Oldham Brandon B Boland Sarah Will Jean-Martin Lapointe Silvia Guionaud Christopher J Rhodes James L Trevaskis | 2018 | World Journal of Gastroenterology2018，24，16： | 7 |
| 2 | Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source显示文摘BACKGROUND The trans-fat containing AMLN(amylin liver non-alcoholic steatohepatitis,NASH)diet has been extensively validated in C57BL/6J mice with or without the Lep^ob/Lep^ob(ob/ob)mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH.Due to a recent ban on trans-fats as food additive,there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice.AIM To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat.METHODS Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat(Primex shortening)substituted by equivalent amounts of palm oil[Gubra amylin NASH,(GAN)diet]for 8,12 and 16 wk.C57BL/6J mice were fed the same diets for 28 wk.AMLN and GAN diets had similar caloric content(40%fat kcal),fructose(22%)and cholesterol(2%)level.RESULTS The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance.Biopsy-confirmed steatosis,lobular inflammation,hepatocyte ballooning,fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet.C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets.CONCLUSION Substitution of Primex with palm oil promotes a similar phenotype of biopsyconfirmed NASH in ob/ob and C57BL/6J mice,making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments. | Michelle L Boland Denise Oro Kirstine S T■lb■l Sebastian T Thrane Jens Christian Nielsen Taylor S Cohen David E Tabor Fiona Fernandes Andrey Tovchigrechko Sanne S Veidal Paul Warrener Bret R Sellman Jacob Jelsing Michael Feigh Niels Vrang James L Trevaskis Henrik H Hansen | 2019 | World Journal of Gastroenterology2019，25，33： | 3 |
| 3 | Neurologic and neuropathologic outcome after middle cerebral artery occlusion in rats显示文摘 | Persson L Hardemark HG Bolander HG | 1989 | Stroke1989，20，5： | 2 |
| 4 | Chest compression force of trained and untrained CPR rescuers显示文摘 | GEDDES L A BOLAND M K TALEYARKHAN P R | 2007 | Cardiovasc Eng2007，7，： | 1 |
| 5 | Flight string models for aircraft fleeting and routing 显示文摘 | C Bamhart N L Boland L W Clarke | 1998 | Transportation Science1998，32，3： | 1 |
| 6 | Coenzyme Q10 : biochemistry, pathophysiology of its deficiency and potential benefit of an increased intake 显示文摘 | Malchair P Van Overmeire L Boland A | 2005 | Rev Med Liege2005，60，1： | 1 |
| 7 | Coenzyme Q10:biochemistry,Pathophysiology of its deficiency and Potential benefit of an increasedintake显示文摘 | Malchair P VanOvermeire L Boland A | 2005 | Rev Med Liege2005，60，1： | 1 |
| 8 | Neuron-specific enolase is a marker of cerebral ischemia and infarct size in rat cerebrospinal fluid显示文摘 | Hardermark HG Persson L Bolander HG | 1988 | Stroke1988，19，9： | 1 |
| 9 | Structural complementation of the catalytic domain of Pseudomonas exotoxin A显示文摘 | Boland E L Van Dyken C M Ducker R M | 2014 | J Mol Biol2014，426，3： | 1 |
| 10 | Accuracy of pupil assessment for the detection of glaucoma: a systematic review and meta-analysis 显示文摘 | CHANG DS XU L BOLAND MV FRIEDMAN DS | 2013 | Ophthalmology2013，120，11： | 1 |
| 11 | Milk protein structure-what can it tell the dairy industry显示文摘 | Sawyer L Barlow P N Boland M J | 2002 | International Dairy Journal2002，12，4： | 1 |
| 12 | Adult mice generated from induced pluripotent stem cells 显示文摘 | Boland M J Hazen J L Nazor K L | 2009 | Nature2009，461，7260： | 1 |
| 13 | Neuronpecific enolase is a marker of cerebral ischemia and infarct size in rat cerebrospinal fluid显示文摘 | Hardemark HG Persson L Bolander HG | 1988 | Stroke1988，19，9： | 1 |
| 14 | Boland on Friedman's methodology: A summtion显示文摘 | Boland L | 1987 | Journal of Economic Issues1987，21，： | 1 |
| 15 | Participation of protein kinase C alpha in 1,25-dihydroxy-vitamin D3 regulation of chick myoblast proliferation and differentiation显示文摘 | Capiati D A Tellez-Inon M T Boland R L | 1999 | Mol Cell Endocrinol1999，153，： | 1 |
| 16 | Anaplastic lymphoma kinase immunoreactivity correlates with ALK gene rearrangement and transcriptional up-regulation in non-small cell lung carcinomas显示文摘 | Boland J M Erdogan S Vasmatzis G Yang P Tillmans L S Johnson M R | 2009 | Hum Pathol2009，40，： | 1 |
| 17 | Distribution of phytate and nutritionally important elements among the morphological components of cereal grains 显示文摘 | O'Dell B L de Boland A R Koirtyohann | 1972 | J Agric Food Chem1972，20，： | 1 |
| 18 | A histological study of corpora lutea from superovulated beef heifers显示文摘 | Vaughan L Fitzpatrick E Boland M P | 1996 | Animal Reproduction Science1996，43，： | 1 |
| 19 | Dominantroles of the polybasic proline motif and copper in thePrP23-89-mediated stress protection response 显示文摘 | Haigh C L Drew S C Boland M P | 2009 | JCell Sci2009，122，0： | 1 |
| 20 | Industrial processing of a novel AI-Cu-Mg powder metallurgy alloy显示文摘 | BOLAND C D HECEMER R L DONALDSON I W | 2013 | Materials Science and Engineering: A2013，559，1： | 1 |
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