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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 | 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 |
| 3 | Impact of tree leaf phenology on growth rates and reproduction in the spring flowering species Trillium erectum(Liliaceae)显示文摘 | Routhier M C Lapointe L | | 0，，03： | 1 |
| 4 | Recent advances in cassava pest management显示文摘 | Bellotti A C Smith L Lapointe S L | 1999 | Annu Rev Entomol1999，44，： | 1 |
| 5 | A novel chemistry to ink separation from mixed paper wasted contaminated with flexoink显示文摘 | Sain M M Marchildon L Lapointe M | 1996 | Nordic Pulp and Paper Research Journal1996，25，1： | 1 |
| 6 | How Phenology Influences Physiology in Deciduous Forest Spring Ephemerals 显示文摘 | Lapointe L | 2001 | Physiologia Plantarum2001，113，2： | 1 |
| 7 | Long-Term Adherence to Evidence-Based Secondary Prevention Therapies in Coronary Artery Disease显示文摘 | L Kristin Newby Nancy M. Allen LaPointe Anita Y. Chen Judith M. Kramer Bradley G. Hammill Elizabeth R. DeLong Lawrence H. Muhlbaier Robert M. Califf | 2006 | Circulation2006，，2： | 1 |
| 8 | Carbon portioning in a split-root system of arbuscular mycorrhizal plants is fungal and plant species dependent显示文摘 | Lerat S Lapointe L Gutjahr S | | 0，，03： | 1 |
| 9 | How phenology influences physiology in deciduous forest spring ephemerals 显示文摘 | Lapointe L | 2001 | Physiologia Plantarum2001，113，2： | 1 |
| 10 | Treatment of post liver transplantation bile duct stricture with self-expandable metallic stent显示文摘 | F. Vandenbroucke M. Plasse M. Dagenais R. Lapointe R. Lêtourneau A. Roy | 2006 | HPB2006，，3： | 1 |
| 11 | How phenology influences physiology in deciduous forest spring ephemerals 显示文摘 | Lapointe L | 2001 | Physiologia Plantarum2001，113，2： | 1 |
| 12 | Implementing the role of a patient - navigator nurse at a university hospital cen-tre显示文摘 | Fillion L de Serres M Lapointe - Goupil R | 2006 | Canadian Oncology Nursing Journal2006，16，1： | 1 |
| 13 | , Molecular dissection of the enkaryotic initiation factor 4E (eIF4E) export-competent RNP 显示文摘 | Topisirovic I Siddiqiu N Lapointe V L | 2009 | EMBO J2009，28，8： | 1 |
| 14 | The alternative respiratory pathway allows sink to cope with changes in carbon availability in the sink-limited plant Erythronium americanum显示文摘 | Gandin A Lapointe L Dizengremel P | 2009 | Journal of experimental botany2009，60，15： | 1 |
| 15 | A Liver Met Survey -based study of 6,025 patients 显示文摘 | Vigan6 L Capussotti L Lapointe R Early recur-rence after liver resection for colorectal metastases: Riskfactors prognosis and treatment | 2014 | Annals of Surgical On-cology2014，21，4： | 1 |
| 16 | Field evaluation of a synthetic female sex pherom one for the leaf mining moth Phyllocnistis citrella ( Lepidoptera: Gracillari idae) in Florida citrus显示文摘 | Lapointe S L Hall D G Murata Y | 2006 | Florida Entomology2006，89，2： | 1 |
| 17 | Production of Exopolysaccharide by Lactobacillus rhamnosus R and Analysis of Its Enzymatic Degradation during Prolonged Fermentation显示文摘 | P L Pham I Dupont D Roy G Lapointe | 2000 | Applied and Environmental Microbiology2000，66，： | 1 |
| 18 | Identification of candi- date prostate cancer genes through comparative expression-profiling of seminal vesicle 显示文摘 | Thompson M Lapointe J Choi Y L | 2008 | Prostate2008，68，11： | 1 |
| 19 | A multilevel model of resistance to information technology implementation 显示文摘 | Lapointe L Rivard S | 2005 | MISQuarterly2005，29，3： | 1 |
| 20 | Muhimorbidity and quality of life in primary care : a systematic review 显示文摘 | Fortin M Lapointe L Hudon C | 2004 | Health Qual Life Out- comes2004，20，1： | 1 |
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