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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 | Identification of Adropin as a Secreted Factor Linking Dietary Macronutrient Intake with Energy Homeostasis and Lipid Metabolism显示文摘 | K. Ganesh Kumar James L. Trevaskis Daniel D. Lam Gregory M. Sutton Robert A. Koza Vladimir N. Chouljenko Konstantin G. Kousoulas Pamela M. Rogers Robert A. Kesterson Marie Thearle Anthony W. Ferrante Randall L. Mynatt Thomas P. Burris Jesse Z. Dong Heathe | 2008 | Cell Metabolism2008，，： | 2 |
| 4 | The molecular basis of vernalization-induced flowering in cereals显示文摘 | Ben Trevaskis Megan N. Hemming Elizabeth S. Dennis W. James Peacock | 2007 | Trends in Plant Science2007，，8： | 2 |
| 5 | Lipids and lipid-based formulations: optimizing the oral delivery of li- pophihc drugs显示文摘 | PORTER C J H TREVASKIS N L CHARMAN W N | 2007 | Nat Rev Drug Discov2007，6，3： | 1 |
| 6 | Lipid-based delivery systems and intestinal lymphatic drug transport: a mecha- nistic update显示文摘 | TREVASKIS N L CHARMAN W N PORTER C J | 2008 | Adv Drug Deliv Rev2008，60，6： | 1 |
| 7 | Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice显示文摘 | Trevaskis JL Griffin PS Wittmer C | 2012 | Am J Physiol Gastrointest Liver Physiol2012，302，8： | 1 |
| 8 | Antiobesity effects of the b-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats显示文摘 | Roth JD Trevaskis JL Wilson J | 2008 | International Journal of Obesity2008，32，： | 1 |
| 9 | Expression and evolution of functionally distinct haemoglobin genes in plants显示文摘 | P.W. Hunt R.A. Watts B. Trevaskis D.J. Llewelyn J. Burnell E.S. Dennis W.J. Peacock | 2001 | Plant Molecular Biology2001，，5： | 1 |
| 10 | Two hemoglobin genes in Arabidopsis thaliana : the evolutionary origins of leghemoglobins显示文摘 | TREVASKIS B WATTS R A ANDERSSON C R | 1997 | Proc Natl Acad Sci USA1997，94，12： | 1 |
| 11 | Increased level of hemoglobin 1 enhances survival of hypoxie stress and promotes early growth in Arabidopsis thaliana 显示文摘 | HUNT P W KLOK E J TREVASKIS B | 2002 | Proc Natl Acad Sci USA2002，99，17： | 1 |
| 12 | Lipid-based delivery systems and intestinal lymphatic drug transport: a mechanistic update 显示文摘 | Trevaskis NL Charman WN Porter CJ | 2008 | Adv Drug Deli Rev2008，60，6： | 1 |
| 13 | Short vegetative phase-like MADS-box genes inhibit floral meristem identity in barley显示文摘 | TREVASKIS B TADEGE M HEMMING M N | 2007 | Plant Physiol2007，143，1： | 1 |
| 14 | Provision of certain carbohydrate-based supplements to pasture-fed sheep, as well as time of havesting of the pasture, influences pH, ammonia concentration and microbial protein synthesis in the mmen显示文摘 | Trevaskis L M Fulkerson W J Gooden J M | 2001 | Aust J Exp Agr2001，41，： | 1 |
| 15 | The relationship between various animal and management factors and milk urea,and its association with reproductive performance of dairy cows grazing pasture显示文摘 | TREVASKIS L M FULKERSON W J | 1999 | Livestock Production Science1999，57，： | 1 |
| 16 | The molecular basis of vernalization-induced flowering in ce- reals显示文摘 | Trevaskis Ben Hemming Megan N Dennis Elizabeth S | 2007 | Trends in Plant Science2007，12，8： | 1 |
| 17 | Expression and evolution of functionally distinct haemoglobin genes in plants 显示文摘 | HUNT P W WATTS R A TREVASKIS B | 2001 | Plant Mol Biol2001，47，5： | 1 |
| 18 | Two hemoglobin genes in Arabidopsis thaliana: The evolutionary o- rigins of leghemoglobins 显示文摘 | TREVASKIS B WATTS R A ANDERSSON C R | 1997 | Proc Natl Acad Sci U S A1997，94，12： | 1 |
| 19 | Glucagon-like peptide-l (GLP-l)receptor agonism improves biochemical and histopathological indices of NASH in mice显示文摘 | TREVASKIS JL GRIFFIN P WITYMER C | 2010 | Hepatology2010，52，1： | 1 |
| 20 | Molecular and cell biology of a family of voltage-dependentan ion chan- nel porins in Lotus japonicus 显示文摘 | WANDREY M TREVASKIS B BREWIN N | 2004 | Plant Physiol2004，134，1： | 1 |
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