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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 frequency and seasonal variations in juvenile outpatients treated in a dermatology polyclinic显示文摘 | Cicek D Kandi B Oguz S | 2008 | Int J Dermatol2008，47，11： | 1 |
| 3 | The prognostic value of mean platelet volume in deeompensated heart failure 显示文摘 | Kandis H Ozhan H Ordu S | 2011 | Emerg Med J2011，28，： | 1 |
| 4 | The prognostic value of mean plate-let volume in decompensated heart failure显示文摘 | Kandis H Ozhan H Ordu S | 2011 | Emerg Med2011，28，7： | 1 |
| 5 | Increased risk of antituberculosis drug-induced hepatotoxicity in individuals with glutathione S-transferase MI null mutation显示文摘 | Roy B Choudhury A Kandy S | 2001 | J Gastroenterol Hepatol2001，16，18： | 1 |
| 6 | Synthesis,antimalarial activity and cytotoxic potential of new monocarbonyl analogues of curcumin显示文摘 | MANOHAR S KHAN S I KANDI S K | 2013 | Bioorg Med Chem Lett2013，23，1： | 1 |
| 7 | An urticarial vasculitis case in-duced by glatiramer acetate显示文摘 | Cicek D Kandi B Oguz S | 2008 | J Dermatolog Treat2008，19，5： | 1 |
| 8 | APOB 3'HVR polymorphism in healthy population: relationships to serum lipid levels 显示文摘 | Alavantie D Glisie S Kandie I | 1998 | Genet Epidemiol1998，15，2： | 1 |
| 9 | Invasive fungal infections: a comprehensive review显示文摘 | Ramana KV Kandi S Bharatkumar VP | 2013 | Am J Infect Dis Micro- biol2013，1，4： | 1 |
| 10 | Invasive fungal infections: a comprehensive review 显示文摘 | KV Ramana S Kandi BP Venkata | 2013 | Am J Infect Dis2013，1，4： | 1 |
| 11 | Invasive fungal infections:a comprehensive review显示文摘 | Ramana K V Kandi S Venkata B P | 2013 | Am J Infect Dis2013，1，4： | 1 |
| 12 | Invasive Fungal Infections:A Comprehensive Review 显示文摘 | Ramana KV Kandi S Bharatkumar PV | 2013 | Am J Infect Dis Microbiol2013，1，4： | 1 |
| 13 | Antimicrobial properties of nanomole- cules: potential candidates as antibiotics in the era of- multi-drug resistance 显示文摘 | Kandi V Kandi S | 2015 | Epidemiol Health2015，37，20： | 1 |
| 14 | genase - 2 expression in Barrett s esophagus显示文摘 | Wilson Kandi HM Tanner G smalley w halter S Rachika A Dabois RNo Cyclo oxy | 2004 | Dig Dis Sci2004，46，8： | 1 |
| 15 | Colour dependency of textile samples on the surface texture显示文摘 | Gorji Kandi S Amani Tehran M Rahmati M | 2008 | Coloration Technology2008，124，6： | 1 |
| 16 | Assessment of pa- tients who presented to the emergency department with mushroom poisoning显示文摘 | Colak S Kandis H Afacan MA | 2015 | Hum Exp Toxieol2015，34，7： | 1 |
| 17 | Antimicrobial properties of nanomolecules : po- tential candidates as antibiotics in the era of multi - drug resistance 显示文摘 | Kandi V Kandi S | 2015 | Epidemiol Health2015，37，20： | 1 |
| 18 | The prognostic value of mean platelet volume in decompensated heart failure显示文摘 | Kandis H Ozhan H Ordu S | | 0，，07： | 1 |
| 19 | The effect of nebulized NaHCO3 treatment on 'RADS' due to chlorine gas inhalation显示文摘 | Aslan S Kandis H Akgun M | 2006 | Inhal Toxicol2006，18，11： | 1 |
| 20 | TLR -4signalling pathway : MyD88 independent pathway up -regulation in chicken breeds upon LPS treatment 显示文摘 | Karnati H K Pasupuleti S R Kandi R | 2015 | Vet Res Commun2015，39，1： | 1 |
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