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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 | Comparative analysis of the exopolysaccharide biosynthesis gene clusters from four strains of Lactobacillua rhamnosus显示文摘 | PEANT B LAPOINTE G GILBERT C | 2005 | Microbiology2005，151，6： | 1 |
| 3 | Evidence for the use of gabapentin in the treatment of diabetic peripheral neuropathy 显示文摘 | Hemstreet B Lapointe M | 2001 | Clin Ther2001，23，4： | 1 |
| 4 | Phosphorus- and nitrogen-limited pho- tosynthesis and growth of Gracilaria tikvahiae (Rho- dophyceae) in the Florida Keys: an experimental field study 显示文摘 | Lapointe B E | 1987 | Mar Biol1987，93，4： | 1 |
| 5 | Nutrient availability to marine macroalgae in siliciclastic versus carbonate-rich coastal waters 显示文摘 | Lapointe B E Littler M M Littler D S | 1992 | Estuaries1992，15，1： | 1 |
| 6 | Productivity and biomass of Thalassia testudinum as related to water column nutrient availability and epiphyte levels:Field observations and experimental studies显示文摘 | Tomasko D A Lapointe B E | 1991 | Marine Ecology Progress Series1991，75，1： | 1 |
| 7 | 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 |
| 8 | Eutrophication and trophic state classification of seagrass communities in the Florida Keys显示文摘 | Lapointe B E Tomasko D A Matzie W R | | 0，，03： | 1 |
| 9 | Tetrodotoxin for mo-derate to severe cancer pain: a randomized, double blind, parallel design multicenter study 显示文摘 | Hagen NA du Souich P Lapointe B | 2008 | J Pain Symptom Manage2008，35，4： | 1 |
| 10 | A multicentre open- label safety and efficacy study of tetrodotoxin for cancer pain 显示文摘 | Hagen NA Lapointe B Ong-Lam M | 2011 | Curr Oneol2011，18，3： | 1 |
| 11 | Defining subregions of Hensens node essential for caudalward movement,midline development and cell survival显示文摘 | CHARRIER J B TEILLET M A LAPOINTE F | 1999 | Development1999，126，21： | 1 |
| 12 | 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 |
| 13 | Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases 显示文摘 | Tetu B Brisson J Lapointe H | 1999 | Breast Cancer Res Treat1999，55，2： | 1 |
| 14 | Eutrophication and trophic state classification of seagrass com- munities in the Florida Keys显示文摘 | Lapoint B E Tomasko D A Matzie W R | 1994 | Bulletin of Marine Science1994，54，3： | 1 |
| 15 | Drift Rhodophyte blooms emerge in Lee County, Florida, USA= Evidence of escalating coastal eutrophication显示文摘 | LAPOINTE B E BEFORD B J | 2007 | Harmful Algae2007，6，： | 1 |
| 16 | Quality of life in HIV disease as measured by the McGill quality of life questionnaire显示文摘 | Cohen SR Hassan SA Lapointe B J | 1996 | AIDS1996，10，12： | 1 |
| 17 | A review of the molecular approaches to investigate the diversity and activity of cheese rnicrobiota显示文摘 | Ndoye B Andriamahery RE LaPointe G | 2011 | Dairy Sci & Technol2011，91，5： | 1 |
| 18 | Comparative analysis of the exopolysaccharide biosynthesis gene clusters from four strains of Lactobacillus rhamnosus显示文摘 | Peant B LaPointe G Gilbert C | 2005 | Microbiology2005，151，6： | 1 |
| 19 | Stormwater nutrient inputs favor growth of non-native macroalgae (Rhodophyta) on O' ahu, Hawaiian Islands显示文摘 | LAPOINTE B E BEDFORD B J | 2011 | Harmful Algae2011，10，3： | 1 |
| 20 | Nutrient availability to marine macroalgae in silieiclastic versus carbonate-rich coastal waters显示文摘 | Lapointe B E Littler M M Littler D S | 1992 | Estuaries1992，15，1： | 1 |
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