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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 | The use of simulation and multiple environmental tracers to quantify groundwater flow in a shallow aquifer显示文摘 | Reilly T E Plummer L N Phillips P J | 1994 | Water Resources Research1994，30，： | 1 |
| 3 | Phosphorus adsorption and desorption in a sandy soil amended with high rates of coal fly ash 显示文摘 | Sims J T | 1995 | Communications in Soil Science and Plant Analysis1995，26，： | 1 |
| 4 | Quantitative analysis of saltwater-freshwater relationships in groundwater systems - A historical perspective 显示文摘 | Reilly T E Goodman A S | 1985 | Journal of Hydrology1985，80，： | 1 |
| 5 | Pyrrolizidine alkaloids in human diet显示文摘 | Prakash A S Pereira T N Reilly P E B | 1999 | Mutat Res1999，443，： | 1 |
| 6 | Breast cancer vaccines:maximizing cancer treatmnet by tapping into host immunity显示文摘 | Emens L A Reilly R T Jaffee E M | 2005 | Endocrine-Related Cancer2005，12，1： | 1 |
| 7 | The use of simulation and multiple environmental tracers to quantify ground-water flow in a shallo waquifer显示文摘 | Reilly T E Plummer L N Phillips P J | 1994 | Water Resources Research1994，30，： | 1 |
| 8 | Non-targeted analysis of petroleum metabolites in groundwater using GC×GC-TOFMS显示文摘 | MOHLER R E O'REILLY K T ZEMO D A | 2013 | Environmental Science & Technology2013，47，10： | 1 |
| 9 | Pharmacology of imatinib(ST1571)显示文摘 | Buchdunger E O'Reilly T Wood J | 2002 | Eur J Cancer2002，38，5： | 1 |
| 10 | Prevention of postpartum stress incontinence in primigravidae with increased bladder neck mobility: a randomised controlled trial of antenatal pelvic floor exercises显示文摘 | REILLY E T C FREEMAN R M WATERFIELD M R | 2014 | BJOG: An International Journal of Obstetrics & Gynaecology2014，121，7： | 1 |
| 11 | A novel particulate influenza vaccine induces longterm and broad-based in mice after oral immunization显示文摘 | Pang G T Clanoy R L O'Reilly S E | 1992 | J Viral1992，66，2： | 1 |
| 12 | Assessment of recent process analytical technology (PAT) trends: a multiauthor review显示文摘 | Simon L L Pataki H Marosi G Meemken F Hungerbiihler K Baiker A Tummala S Glennon B Kuentz M Steele G Kramer H J M Rydzak J W Chen Z Morris J Kjell F Singh R Gani R Gernaey K V Louhi-Kultanen M O'Reilly J Sandler N Antikainen 0 Yliruusi J Frohberg P Ulrich J Braatz R D Leyssens T von Stosch M Oliveira R Tan R B H Wu H Khan M O'Grady D Pandey A Westra R Delle-Case E Pape D Angelosante D Maret Y Steiger 0 Lenner M Abbou-Oucherif'K Nagy Z K Litster J D Kamaraju V K Chiu M-S | 2015 | Organic Process Research & Development2015，19，1： | 1 |
| 13 | 显示文摘 | Beechinor J T Mcglynn E O'reilly M Crean G M | 1997 | Microelectronic Engineering1997，33，14： | 1 |
| 14 | Carcinogenicity risk assessment supports the chronic safety of dapagliflozin,an inhibitor of sodium-glucose co-transporter 2,in the treatment of type 2 diabetes mellitus显示文摘 | Reilly T P Graziano M J Janovitz E B | 2014 | Diabetes Ther2014，5，1： | 1 |
| 15 | Pharmacology of imatinib (STI571) 显示文摘 | Buchdunger E O'Reilly T | 2002 | Eur J Cancer2002，38，： | 1 |
| 16 | The Hf isotope composition of cratonic mantle: LAM-MC-ICPMS analysis of zircon megacrysts in kimberlites 显示文摘 | Griffin W L Pearson N J Belousova E Jackson S E van Achterbergh E O'Reilly S T Shee S R | 2000 | Geochim Cosmochim Acta2000，64，1： | 1 |
| 17 | Knockdown resistance to DDT and pyrethroids:from target-site mutations to molecular modelling显示文摘 | Davies T G E O'Reilly A O Field L M | | 0，，11： | 1 |
| 18 | Biology and adoptive cell therapy of Epstein-Barr virus-associated lymphoproliferative disorders in recipients of marrow allografts显示文摘 | O'Reilly R J Small T N Papadopoulos E | 1997 | Immunol Rev1997，157，： | 1 |
| 19 | Quantitative analysis of saltwater - freshwater relationships in groundwater systems-A historical perspective显示文摘 | REILLY T E GOODMAN A S | 1985 | Journal of Hydrology1985，80，： | 1 |
| 20 | Analysis of work-rate in soccer显示文摘 | DRUST B REILLY T RIENZI E | 1998 | Sports Exe Injury1998，4，4： | 1 |
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