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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 | The mechanism of enzyme in the collagen extracting 显示文摘 | MILLER E J RHODES R K | 1982 | Methods in enzymology1982，82，： | 2 |
| 3 | DNA vaccination of infants in the presence of maternal antibody: a measles model in the primate显示文摘 | Mary Premenko-Lanier Paul A Rota Gary Rhodes David Verhoeven Dan H Barouch Nicholas W Lerche Norman L Letvin William J Bellini Michael B McChesney | 2003 | Virology2003，，1： | 2 |
| 4 | Multiple forms of hydroxycinnamate:CoA ligase in etiolated pea seedling显示文摘 | RHODES M J C | 1977 | Phytochemistry1977，16，： | 1 |
| 5 | Myelopoiesis in the zebrafish, Danio rerio显示文摘 | Bennett CM Kanki JP Rhodes J | 2001 | Blood2001，98，3： | 1 |
| 6 | Animal and temporal effects on ovarian follicular dynamics in Brahman heifers显示文摘 | Rhodes J M de Ath G Entwisfle K W | 1995 | Anita Reprod Sci1995，38，： | 1 |
| 7 | Content - Centered Collaboration Spaces in the Cloud 显示文摘 | ERICKSON J S SPENCE S RHODES M | 2009 | IEEE Internet Computing2009，13，5： | 1 |
| 8 | Post-failure behaviour of box section beams under pure bending (an experimental study) 显示文摘 | KOTELKO M LIM T H RHODES J | 2000 | Thin-walled Structures2000，38，2： | 1 |
| 9 | Conversion of waste cooking oil to biodiesel using ferricsulfate and supercritical methanol processes显示文摘 | Prafulla Patil Shuguang Deng Isaac Rhodes J | 2010 | Fuel2010，89，2： | 1 |
| 10 | High levels of endemicity of 3-chlorobenzoate-degrating soil bacteria显示文摘 | FULTHORPE R R RHODES A N TIEDJE J M | 1998 | Applied and Environmental Microbiology1998，64，5： | 1 |
| 11 | Free radicals,metals and antioxidants in oxidative stress-induced cancer显示文摘 | Valko M Rhodes C J Moncol J | 2006 | Chem Biol Interact2006，160，1： | 1 |
| 12 | Prevalence of arrhythmias during exercise stress testing in patients with congenital heart disease and severe right ventricular con- duit dysfunction显示文摘 | Priromprintr B Rhodes J Silka MJ | 2014 | Am J Cardiol2014，114，3： | 1 |
| 13 | Vaccine Safety Datalink project:a new tool for improving vaccine safety monitoring显示文摘 | CHEN R T GLASSER J W RHODES P H | 1997 | Pediatrics1997，99，6： | 1 |
| 14 | Predicion of incompressible flow in a labyrinth seal 显示文摘 | RHODE D L DEMKO J A TRAEGNER U K | 1986 | ASME Journal of Fluids Engineering1986，108，： | 1 |
| 15 | Optimal linear image combination显示文摘 | Rowe B Hirata C Rhodes J | 2011 | The Astronomical Journal2011，74，： | 1 |
| 16 | The Prediction andMeasurement of incompressible flow in a labyrinth seal 显示文摘 | DEMKO J A MORRISON G L RHODE D L | 1980 | ASME Journal of Engineering Gas Turbines Power1980，111，4： | 1 |
| 17 | Fear appeal messages affect accessibility of attitudes toward the threat and adaptive behaviors显示文摘 | Roskos ED Yu J Rhodes N | 2004 | Communication Monographs2004，71，1： | 1 |
| 18 | Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis:role of protein kinaseB显示文摘 | Li L El Kholy W Rhodes C J | 2005 | Diabetologia2005，48，： | 1 |
| 19 | Impact of air staging on the fate of NO and N2O in a circulating fluidized-bed combustor 显示文摘 | Wang X S Gibbs B M Rhodes M J | 1994 | Combustion and Flame1994，99，34： | 1 |
| 20 | Performance of large-aperture optical:switches for high energy inertial-confinement fusion lasers显示文摘 | Mark A Rhodes B Woods J J DeYoreo | 1995 | Applied Optics1995，34，53： | 1 |
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