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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 | Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice显示文摘 | Collins Meredith A Bednar Filip Zhang Yaqing Brisset Jean-Christophe Galbán Stefanie Galbán Craig J Rakshit Sabita Flannagan Karen S Adsay N Volkan di Magliano Marina Pasca | 2012 | EN2012，，： | 3 |
| 3 | Entry of hepatitis B and C viruses — recent progress and future impact显示文摘 | Thomas F Baumert Luke Meredith Yi Ni Daniel J Felmlee Jane A McKeating Stephan Urban | 2013 | Current Opinion in Virology2013，，： | 3 |
| 4 | Fluorescence resonance energy transfer studies on the interaction between the lactate transporter MCT1 and CD147 provide information on the topology and stoichiometry of the complex in situ显示文摘 | Wilson M C Meredith D Halestrap A P | 2002 | J Biol Chem2002，277，5： | 1 |
| 5 | The evolution of the intellectual structure of operations management-1980-2006: A citation/co-citation analysis显示文摘 | Pilkington A Meredith J | 2009 | Journal of Operations Management2009，27，3： | 1 |
| 6 | Trade Defection and Trade Depression 显示文摘 | Bown Chad P Crowley Meredith A | 2005 | Federal Reserve Bank of Chicago Working Paper2005，，26： | 1 |
| 7 | Nutrient data on chestnuts consumed in the United States显示文摘 | McCARTHY M A MEREDITH F I | 1988 | Economic Botany1988，42，1： | 1 |
| 8 | Agrobacterium-mediated transformation of Lilium 显示文摘 | COHEN A MEREDITH C P SANIEWSKI M | 1992 | Acta Hort1992，325，： | 1 |
| 9 | Identification of associations between SSR markers and fiber traits in an exotic germplasm derived from multiple crosses among Gossypium tetraploid species显示文摘 | Zeng L H Meredith W R Jr Gutiérrez O A | 2009 | Theor Appl Genet2009，119，： | 1 |
| 10 | Injected bubble populations in seawater and fresh water measured by a photographic method显示文摘 | Bruce D Jhonson | 1995 | Journal of Geophysical Research1995，100，4： | 1 |
| 11 | Structure and function of eukary- otic peptide transporters显示文摘 | Meredith D Boyd C A R | 2000 | Life Sci2000，57，： | 1 |
| 12 | Grain refinement of aluminium alloys by inoculation 显示文摘 | GREER A L COOPER P S MEREDITH M W SCHNEIDER W SCHUMACHER P SPITTLE J A | 2003 | Advanced Engineering Materials2003，5，： | 1 |
| 13 | Role of endothelium in ischemic coronary syndrom显示文摘 | MEREDITH I T ANDERSON T J UEHATA A | 2003 | Am J Cardiol2003，72，8： | 1 |
| 14 | How to Evaluate the duration of blood pressure control: the trough:peak ratio and 24-hour monitoring显示文摘 | MEREDITH P A | 1998 | Cardiovasc Pharmacol1998，31，2： | 1 |
| 15 | The Effect of Water Pressure on Hydrocarbon Generation Reactions : Some Inferences from Laboratory Experiments显示文摘 | Carr A D Shape C E Meredith W | 2009 | Petroleum Geoscience2009，，15： | 1 |
| 16 | Close encounters of the monoamine kind: immune cells betray their nervous disposi- tion显示文摘 | Meredith EJ Chamba A Holder MJ | 2005 | Immunology2005，115，3： | 1 |
| 17 | Molecular signa- tures of end-stage heart failure显示文摘 | Lin D Hollander Z Meredith A | 2011 | J Card Fail2011，17，10： | 1 |
| 18 | Comparison of the clinical pharmacokinetics and concentration-effect relationships for medroxalol and labetalol显示文摘 | Elliot H L Meredith P A Sumner D J | 1984 | Br J Clin Pharmac1984，17，5： | 1 |
| 19 | Women's Jobs, Men's Jobs: Sex Segregation and Emotional Labor 显示文摘 | Mary E G Meredith A N | 2004 | Public Administra- tion Review2004，64，3： | 1 |
| 20 | The Evolution of the Intellectual Structure of Operations Management 1980-2006: A Citation/Co-Citation Analysis显示文摘 | Pilkington A Meredith J | 2009 | Journal of Operations Management2009，3，27： | 1 |
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