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| 1 | Prolonged high-fat-diet feeding promotes non-alcoholic fatty liver disease and alters gut microbiota in mice显示文摘BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used to alleviate NAFLD, successful treatment options are limited. One of the main barriers to finding safe and effective drugs for long-term use in NAFLD is the fast initiation and progression of disease in the available preclinical models. Therefore, we are in need of preclinical models that (1) mimic the human manifestation of NAFLD and (2) have a longer progression time to allow for the design of superior treatments. AIM To characterize a model of prolonged high-fat diet (HFD) feeding for investigation of the long-term progression of NAFLD. METHODS In this study, we utilized prolonged HFD feeding to examine NAFLD features in C57BL/6 male mice. We fed mice with a HFD (60% fat, 20% protein, and 20% carbohydrate) for 80 wk to promote obesity (Old-HFD group, n = 18). A low-fat diet (LFD)(14% fat, 32% protein, and 54% carbohydrate) was administered for the same duration to age-matched mice (Old-LFD group, n = 15). An additional group of mice was maintained on the LFD (Young-LFD, n = 20) for a shorter duration (6 wk) to distinguish between age-dependent and age-independent effects. Liver, colon, adipose tissue, and feces were collected for histological and molecular assessments.RESULTS Prolonged HFD feeding led to obesity and insulin resistance. Histological analysis in the liver of HFD mice demonstrated steatosis, cell injury, portal and lobular inflammation and fibrosis. In addition, molecular analysis for markers of endoplasmic reticulum stress established that the liver tissue of HFD mice have increased phosphorylated Jnk and CHOP. Lastly, we evaluated the gut microbial composition of Old-LFD and Old-HFD. We observed that prolonged HFD feeding in mice increased the relative abundance of the Firmicutes phylum. At the genus level, we observed a significant increase in the abundance of Adercreutzia, Coprococcus, Dorea, and Ruminococcus and decreased relative abundance of Turicibacter and Anaeroplasma in HFD mice. CONCLUSION Overall, these data suggest that chronic HFD consumption in mice can mimic pathophysiological and some microbial events observed in NAFLD patients. | Kandy T Velázquez Reilly T Enos Jackie E Bader Alexander T Sougiannis Meredith S Carson Ioulia Chatzistamou James A Carson Prakash S Nagarkatti Mitzi Nagarkatti E Angela Murphy | 2019 | World Journal of Hepatology2019，11，8： | 6 |
| 2 | Ron receptor-dependent gene regulation in a mouse model of endotoxin-induced acute liver failure显示文摘BACKGROUND:Prior experimentation has shown that loss of the tyrosine kinase(TK) signaling domain of the Ron receptor leads to marked hepatocyte protection in a model of lipopolysaccharideinduced acute liver failure(ALF) in D-galactosamine(GalN)sensitized mice.The aim of this study was to identify the role of Ron in the regulation of hepatic gene expression.METHODS:Microarray analyses were performed on liver RNA isolated sequentially from wild-type(WT) and TK-/mice during the progression of ALF.Gene array data were validated using Western and immunohistochemistry analyses as well as with ex vivo culture systems.RESULTS:At baseline,101 genes were differentially expressed between WT and TK-/-livers,which regulate processes involved in hypoxia,proliferation,apoptosis and metabolism.One hour after ALF induction,WT livers exhibited increased cytokine expression compared to TK-/-livers,and after 4 hours,an induction of suppressor of cytokine signaling(SOCS) genes as well as JAK-STAT pathway activation were prominent in TK-/livers compared to controls.CONCLUSION:Our studies suggest a novel hepato-protective mechanism in Ron TK-/-mice wherein increased and sustained SOCS production and JAK-STAT activation in the hepatocyte may inhibit the destructive proinflammatory milieu and promote survival factors which blunt hepatic death and the ensuing development of ALF. | Rishikesh M Kulkarni Louis W Kutcher William D Stuart Daniel J Carson Mike A Leonis Susan E Waltz | 2012 | Hepatobiliary & Pancreatic Diseases International2012，11，4： | 3 |
| 3 | Analysis of peridural scar formation and its prevention after lumbar laminotomy and discectomy in dogs显示文摘 | SONGER M N RAUSCHNING W CARSON E W | 1995 | Spine1995，20，5： | 1 |
| 4 | Sequencing and Valuating Public Goods显示文摘 | Carson R T Flores N E Hanemann M | 1998 | Journal of Environmental Eeonomics and Management1998，，36： | 1 |
| 5 | The Ashworth Scale: a reliable and reproducible method of measuring spasticity 显示文摘 | Lee KC Carson L Kinnin E | 1989 | Neurorehabil Neural Repair1989，3，4： | 1 |
| 6 | Drought stress and tropical for-est woody seedlings:Effect on community structure and composi-tion显示文摘 | BUNKER D E CARSON W P | 2005 | Journal of Ecology2005，93，4： | 1 |
| 7 | A Method to Make Use of Thermal Infrared Temperature and NDVI Measurements to Infer Surface Soil Water Content and Fractional Vegetation Cover 显示文摘 | Carson T N Gillies R R Perry E M | 1994 | Remote Sensing Reviews1994，，9： | 1 |
| 8 | A multilevel investigation of antecedents and consequences of team member boundary-spanning behavior显示文摘 | Marrone J A Tesluk P E Carson J B | 2007 | Academy of Management Journal2007，50，6： | 1 |
| 9 | A Multilevel Investigation of Antecedents and Conse- quences of Team Member Boundary-Spanning Behav- ior显示文摘 | MARRONE J A TESLUK P E CARSON J B | 2007 | Academy of Management Journal2007，50，6： | 1 |
| 10 | Reversible mid- dle cerebral artery occlusion without cranieetomy in rats 显示文摘 | Longa E Z W einstein P R Carson S | 1989 | Stroke1989，20，1： | 1 |
| 11 | Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial显示文摘 | Meduri GU Golden E Freire AX Taylor E Zaman M Carson S J | 2007 | Chest2007，131，4： | 1 |
| 12 | The Importance of Storage, Transfer and Collection 显示文摘 | KNOWLTON T M CARSON J W KLINZING G E | 1994 | Chemical Engineering Progress1994，90，1： | 1 |
| 13 | ARB can decrease heart failure combined with AF显示文摘 | Maggloni A P Latini R Carson P E | 2005 | Am Heart J2005，149，： | 1 |
| 14 | Shared leadership in teams= An investigation of anteeedent conditions and per- formance显示文摘 | Carson J B Tesluk P E and Marrone J A | 2007 | Academy of Management Journal2007，50，5： | 1 |
| 15 | Efficacy and pharmaeokinetics of bacteriophage therapy in treatment of subciinieal Staphylococcus aureus mastitis in lactating dairy cattle 显示文摘 | Gill J J Paean J C Carson M E eta/ | 2006 | Antimicrobial Agents and Chemotherapy2006，50，9： | 1 |
| 16 | Reversible middle cerebral artery:occlusion without craniotomy in rats 显示文摘 | LONGA E Z WEINSTEIN P R CARSON S | 1989 | Stroke1989，19，20： | 1 |
| 17 | The role of GABA in the mediation and percept ion of pain显示文摘 | ENNA S J MC CARSON K E | 2006 | Adv Pharmacol2006，54，： | 1 |
| 18 | Aberrant extracellular and dendritic cell (DC) surface expression of heat shock protein (hsp)70 in the rheumatoid joint: possible mechanisms of hsp/DC-mediated cross-priming 显示文摘 | Martin C A Carsons S E Kowalewski R | 2003 | J Immunol2003，171，11： | 1 |
| 19 | Contingent Valuation and Revealed Preference Methodologies: Com- paring the Estimates for Quasi-public Goods 显示文摘 | Carson R T Flores N E Martin K M | 1996 | Land Economics1996，71，1： | 1 |
| 20 | Atrial fibrillation in pregnancy associated with oral terbutaline显示文摘 | Carson M P Fisher A J Scorza W E | 2002 | Obstet Gynecol2002，100，5： | 1 |
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