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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 | Long-term follow-up after neoadjuvant chemotherapy for high-risk cervical cancer during pregnancy 显示文摘 | Bader AA Petru E Winter R | 2007 | Gynecol Oncol2007，105，： | 1 |
| 3 | A physical approach to protein structure prediction 显示文摘 | CRIVELLI S ESKOW E BADER B LAMBERTI V BYRD R SCHNABEL R HEAD-GORDON T | 2002 | Biophysical Journal2002，82，1： | 1 |
| 4 | Aspect2 oriented programming显示文摘 | TZILLA E FILMAN R E BADER A | 2001 | Communications of the ACM2001，44，10： | 1 |
| 5 | Coordination Chemistry and Catalysis with Hemilabile Oxygen-Phosphorus Ligands显示文摘 | Bader A Linder E | 1991 | Coord Chem Rev1991，108，： | 1 |
| 6 | Integrated processing equipment显示文摘 | Bader M E Hall R P Strasser G | 1990 | Solid State Technology1990，33，5： | 1 |
| 7 | Relevance of microbial coculture fermentations in biotechnology显示文摘 | Bader J Mast -Gerlach E Popovic MK et (1/ | 2010 | Journal of Applied Microbiology2010，109，2： | 1 |
| 8 | Structure and function of the kidney in diabetic glomerulosclerosis:correlations between morphological and functional parameters显示文摘 | Bader R Bader E Grung K E | 1980 | Pathol Res Pract1980，167，： | 1 |
| 9 | Integrated processing equipment显示文摘 | M E Bader R P Hall G Strasser | 1990 | Solid State Technology1990，33，5： | 1 |
| 10 | Hard/soft magnetic heterostructures : model exchange - spring magnets 显示文摘 | FULLERTON E E JIANG J S BADER S D | 1999 | J Magn Magn Mater1999，200，1： | 1 |
| 11 | Production of transgenic models in hypertension 显示文摘 | Popova E Bader M Krivokharchenko A | 2004 | Methods Mol Med2004，108，： | 1 |
| 12 | Temperature-dependent biquadratic coupling in antiferromagnetically coupled Fe/FeSi multilayers显示文摘 | Fullerton E E Bader S D | 1996 | Phys Rev B1996，53，： | 1 |
| 13 | 显示文摘 | BADER A LINDNER E | 1991 | Coord Chem Rev1991，108，1： | 1 |
| 14 | Initial presentation of childhood - onset systemic lupus erythematosus: A French multicenter study显示文摘 | Bader - Meunier B Armengaud JB Haddad E | 2005 | J Pediatr2005，146，5： | 1 |
| 15 | HypE: an algorilhm for fast hy- pervolume-based many-objective optimization 显示文摘 | Bader J Zitzler E | 2011 | Evolutionary Computation2011，19，1： | 1 |
| 16 | Intensified surveillance after surgery for colorectal cancer significantly improves survival 显示文摘 | Laubert T Bader F G Oevermann E | 2010 | Eur J Med Res2010，15，1： | 1 |
| 17 | LDL stimulates chemotaxis of human monocytes through a cyclooxygenase-dependent pathway显示文摘 | Kreuzer J Denger S Jahn L Bader J Ritter K von Hodenberg E | 1996 | Arterioscler Thromb Vasc Biol1996，16，12： | 1 |
| 18 | Reconstruction of liver tissue in vitro: geometry of characteristic flatbed,hollow fiber,and spouted bed bioreactors with reference to the in vivo liver显示文摘 | Bader A Knop E Fruhauf N | 1995 | Artif Organs1995，19，9： | 1 |
| 19 | Increased expression of the multidrug resistance-associated protein gene in replased acute leukemia显示文摘 | Schneider E Cowan K Ⅱ Bader Ⅱ | 1995 | Blood1995，85，： | 1 |
| 20 | Hyp E:An algorithm for fast hypervolume-based many-objective optimization显示文摘 | Bader J Zitzler E | 2011 | Evolutionary computation2011，19，1： | 1 |
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