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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 | Keratoeysticodontogenictumour: reclassifica- tion of the odontogenickeratocyst from cyst to tumour 显示文摘 | Madras J Lapointe H | 2008 | Tes Dent J2008，125，5： | 1 |
| 3 | Hormonal and spatial regulation of nitric oxide synthases(NOS)(neuronal NOS,inducible NOS,and endothelial NOS)in the oviducts显示文摘 | Lapointe J Roy M St-Pierre I | 2006 | Endocrinology2006，147，12： | 1 |
| 4 | An artificial diet for Diaprepes abbreviatus (Coleoptera: Curculionidae) optimized for larval snrvival显示文摘 | Lapointe S L Niedz R P Evens T J | 2010 | FloridaEntomologist2010，93，1： | 1 |
| 5 | The submitochondrial distribution of ubiquinone affects respiration in long-lived Mclk1+/-mice显示文摘 | Jérme Lapointe Ying Wang Eve Bigras | 2012 | Cell Biol2012，199，2： | 1 |
| 6 | Laboratory and field performance of polymer-modified cement- based repair mortars in cold climates显示文摘 | MIRZA J MIRZA M S LAPOINTE R | 2002 | Constr Build Mater2002，16，6： | 1 |
| 7 | The role of human and mouse hepatic scavenger receptor class B type I (SR-BI) in the selective uptake of low-density lipoprotein-cholesteryl esters 显示文摘 | Rhainds D Brodeur M Lapointe J | 2003 | Biochemistry2003，42，24： | 1 |
| 8 | Early closure of fistula after hypospadias surgery using N-butyl cyanoacrylate:preliminary results显示文摘 | Lapointe S P N-Fekete C Lortat J S | 2002 | J Urology2002，168，42： | 1 |
| 9 | Keratocystic odontogenic tumour:reclassification of the odontogenic keratocyst from cyst to tumour显示文摘 | Madras J Lapointe H | 2008 | J Can Dent Assoc2008，74，2： | 1 |
| 10 | Angiotensin II induced hypertrophy of adult rat cardiomyocytes is blocked by nitric oxide显示文摘 | RITCHIE R H SCHIEBINGER R J LAPOINTE M C | 1998 | Am J Physiol Heart Circ Physiol1998，275，42： | 1 |
| 11 | The retinoic acid synthesisgene ALDH1a2 is a candidate tumor suppressor in prostate cancer显示文摘 | Kim H Lapointe J Kaygusuz G | 2005 | Cancer Res2005，65，18： | 1 |
| 12 | Computed tomographic dignosis of intraventricular hemorrhage显示文摘 | GRAEB D A ROBERTSON W D LAPOINTE J S | 1982 | Radiology1982，143，1： | 1 |
| 13 | Keratocystic odontogenic tumour:reclassification of the odontogenic keratocyst from cyst to tumour显示文摘 | Madras J Lapointe H | 2008 | J Can Dent Assoc2008，74，2： | 1 |
| 14 | Gene expression profiling identifies clinically relevant subtypes of prostate cancer 显示文摘 | Lapointe J Li C Higgins J P | 2004 | Proc Natl Acad Sci U S A2004，101，3： | 1 |
| 15 | Computed tomographic diagnosis of intraventricular hemorrhage显示文摘 | Robertson W D Lapointe J S | 1982 | Radiology1982，143，1： | 1 |
| 16 | Diversity and relative strength of tandem promoters for the antibioticresistance genes of several integrons显示文摘 | Levesque C Brassard S Lapointe J | 1994 | Gene1994，142，1： | 1 |
| 17 | Monolithically integrated asymmetric graded and step-index couplers for microphotonic waveguides显示文摘 | Delage A Janz S Lapointe J | | 0，，01： | 1 |
| 18 | Diversity and relative strength of tandem promoters for the antibiotic-resistance genes of several integrons显示文摘 | Levesque C Brassard S Lapointe J | 1994 | Gene1994，142，1： | 1 |
| 19 | Statistical significance of the matrix correlation coefficient for comparing independent phylogenetics trees 显示文摘 | LAPOINTE F J LEGENDRE P | 1992 | Systematic Biology1992，41，3： | 1 |
| 20 | Some aspects of the growth and yield of Gracilaria tikvahiae in culture显示文摘 | Lapointe B E Ryther J H | 1985 | Aquaculture1985，15，： | 1 |
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