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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 | Mechanical properties of a biodegradable bone regeneration scaffold显示文摘 | Porter B D Oldham J B He S L | 2000 | J Biomech Eng2000，122，3： | 2 |
| 3 | Myostatin regulation during skeletal muscle regeneration显示文摘 | Kirk S Oldham J Kambadur R | 2000 | Cell Physiol2000，184，3： | 2 |
| 4 | IL-33,an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines显示文摘 | Schmitz J Owyang A Oldham E | 2005 | Immunity2005，23，5： | 1 |
| 5 | IL-33,an intedeukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines显示文摘 | Schmitz J Owyang A Oldham E | 2005 | Immunity2005，23，5： | 1 |
| 6 | IL-33, an interleukin-1-likecytokine that signals via the IL-1 receptor-related protein ST2 andinduces T helper type 2-associated cytokines显示文摘 | Schmitz J Owyang A Oldham E | 2005 | Immunity2005，23，5： | 1 |
| 7 | Cone-beam-CT guided radiation therapy: technical implementation 显示文摘 | Letourneau D Wong J W Oldham M | 2005 | Radiother Oncol2005，75，3： | 1 |
| 8 | Listen while you work? Quasi-experimental rela- tions between personal-stereo headset use and em- ployee work responses显示文摘 | Oldham G R Cummings A Mischel L J | 1995 | Journal of Applied Psy- chology1995，80，5： | 1 |
| 9 | Proportions of volatile fatty acids in relation to the chemical composition of feeds based on grass silage显示文摘 | FRIGGENS N C OLDHAM J D DEWHURST R J | 1998 | Journal of Dairy Science1998，81，5： | 1 |
| 10 | Enhancing creative performance:Effects of expected developmental assessment strategies and creative personality显示文摘 | Zhou J Oldham G R | 2001 | Journal of Creative Behavior2001，35，3： | 1 |
| 11 | Identification of the transcriptional targets of FOXP2,a gene linked to speech and language,in developing human brain显示文摘 | Spiteri E Konopka G Coppola G Bomar J Oldham M Ou J | | 0，，06： | 1 |
| 12 | Quantitative determination of lysozyme-ligand binding in the solution and gas phases by electrospray ionisation mass spectrometry显示文摘 | VEROS C T OLDHAM N J | 2007 | Rapid Communications in Mass Spectrometry2007，21，21： | 1 |
| 13 | IL-33,an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines显示文摘 | Schmitz J Owyang A Oldham E | 2005 | Immunity2005，23，5： | 1 |
| 14 | Effects of supplemental vi- tamin A or β-carotene during the dry period and early lacta- tion on udder health 显示文摘 | OLDHAM E R EBERHART R J | 1991 | J Dairy Sci1991，74，： | 1 |
| 15 | Glucose and urea kinet- ics in early lactation显示文摘 | Bruckental I Oldham J D Sutton J D | 1980 | Br J Nutr1980，44，： | 1 |
| 16 | Effects of supplementalVitamin A orβ-carotene during the dry period and early lactationon udder health显示文摘 | Oldham E R Eberhart R J Muller L D | 1991 | Journal of Dairy Science1991，74，11： | 1 |
| 17 | IL-33, an interleukin-l-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines 显示文摘 | Schmitz J Owyang A Oldham E | 2005 | Immunity2005，23，5： | 1 |
| 18 | The Effects of Personal and Contextual Characteristics on Creativity : Where Should We Go from Here? 显示文摘 | Shalley C E Zhou J Oldham G R | 2004 | Journal of Management2004，30，6： | 1 |
| 19 | IL - 33, an interleukin - 1 - like cytokine that signals via the IL - 1 receptor - related protein ST2 and induces T helper type 2 - associated cytokines 显示文摘 | Sehmitz J Owyang A Oldham E Song Y Murphy E McClanahan TK | 2005 | Immunity2005，23，： | 1 |
| 20 | Image recovery and segmentation using competitive learning in a neighborhood system显示文摘 | Li Chengcheng Oldham W J B | 2001 | Neural Networks2001，2，： | 1 |
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