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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 | New PDC bit design reduces vibrational problems显示文摘 | Graham M W Will L A | 1995 | Oil and Gas Journal1995，93，22： | 1 |
| 3 | Characterization of lipidstorage associated proteins induced in crop tissue by pro-lactin显示文摘 | HORSEMAN N D WILL C L | 1984 | J Comp Physiol B1984，，154： | 1 |
| 4 | On the Low-pressure Synthesis of Cubic Boron Nitride显示文摘 | B P Singh V L Solozhenko G Will | 1995 | Diamond and Related Materials1995，4，： | 1 |
| 5 | Larviculture techniques of Chinese mitten crab Eriocheir sinensis 显示文摘 | Sui L Y Wille M Cheng Y X | 2011 | Aquaculture2011，315，12： | 1 |
| 6 | Changes in weight of the pharyngeal glandand haemolymph titres of juvenile hormone, protein and vitellogenin in worker honey bees 显示文摘 | Fluri P Luscher M Wille H Gerig L | 1992 | Journal of Insect Physiology1992，28，： | 1 |
| 7 | Maximum likelihood identification of Wiener models 显示文摘 | Hagenblad A Ljung L Wills A | 2008 | Automatiea (S0005-t098)2008，，： | 1 |
| 8 | 查看详情显示文摘 | Khare A Wills A W Ammerman L M | | 0，，： | 1 |
| 9 | Prognostic factors for mortality following interhospital transfers to the medical intensive care unit of a tertiary referral center显示文摘 | Durairaj L Will JG Torner JC | | 0，，： | 1 |
| 10 | On the Low-Pressure Synthesis of Cubic Boron Nitride显示文摘 | Singh B P Solozhenko V L Will G | 1995 | Diamond and Related Materials1995，4，： | 1 |
| 11 | Inflammato- ry (pseudosarcomatous) myofibroblastic tumor of the bladder显示文摘 | Lakshmanan Y Wills M L Gearhart J P | 1997 | Urology1997，50，： | 1 |
| 12 | Nitric oxide degradation in oxygen atmospheres and rate of uptake by horticultural produce显示文摘 | Soegiarto L Wills RBH Seberry JA | 2003 | Postharvest Biology and Technology2003，28，： | 1 |
| 13 | Macadamia nut consumption lowers plasma total and LDL cholesterol levels in hypercholesterolemic men显示文摘 | Garg M L Blake R J Wills R B | 2003 | Journal of Nutrition2003，133，4： | 1 |
| 14 | Computational-complexity of the ground-state determination of atomic clusters显示文摘 | Wille L T Vennik J | 1985 | Journal of Physics a-Mathematical and General1985，18，8： | 1 |
| 15 | Assessing subtle memory impairments in the everyday memory performance of brain injured people:exploring the potential of the Extended Rivermead Behavioural Memory Test显示文摘 | Wills P Clare L Shiel A | 2000 | Brain Injury2000，14，8： | 1 |
| 16 | Isolation of an active step Ⅰ spliceosome and composition of its RNP core 显示文摘 | Bessonov S Anokhina M Will C L et ol | 2008 | Nature2008，452，7189： | 1 |
| 17 | U2 snRNA-protein contactsin purified human 17S U2 snRNPs and in spliceosomal A and B comple-xes显示文摘 | DYBKOV O WILL C L DECKERT J | 2006 | Molecular and Cellular Biology2006，26，7： | 1 |
| 18 | Fossil vertebrate and invertebrate tracks from boreholes through the Bunter series (Triassic) of Worcestershire 显示文摘 | Wills L J Sarjeant W A S | 1970 | Mercian Geol1970，3，： | 1 |
| 19 | The splieeosome: design principles of a dynamic RNP machine显示文摘 | Wahl M C Will C L Luhrmann R | 2009 | Cell2009，136，4： | 1 |
| 20 | A prospective,randomized comparison of the use versus non-use of topical corticosteroids after laser in situ keratomileusis显示文摘 | Price FW Jr Willes L Price M | 2001 | Ophthalmology2001，108，7： | 1 |
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