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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 | Endostatin:an endogenous inhibitor of angiogenesis and tumor growth显示文摘 | O'Reilly MS Boehm T Shing Y | | 0，，： | 4 |
| 3 | A rat model of bone cancer pain显示文摘 | S.J Medhurst K Walker M Bowes B.L Kidd M Glatt M Muller M Hattenberger J Vaxelaire T O’Reilly G Wotherspoon J Winter J Green L Urban | 2002 | Pain2002，，： | 2 |
| 4 | Endostatin: an endogenous inhibitor of angiogenesis and tumor growth 显示文摘 | O'Reilly MS Boehm T Shine Y | 1997 | Cell1997，88，2： | 1 |
| 5 | Cloning of a human seventransmemhrane domain receptor, LESTR,that is highly expressed in leukocytes显示文摘 | Loetscher M Geiser T O'Reilly T | 1994 | J Biol Chem1994，269，1： | 1 |
| 6 | Endostatin:An endogenous inh ibitor of angiogenesis and tumor growth显示文摘 | O'Reilly MS Boehm T Shing Y | 1997 | Cell1997，88，： | 1 |
| 7 | Endostatin:An endogenous inhibitor of angiogenesis and tumor growth显示文摘 | O'Reilly MS Boehm T Shing Y | 1997 | Cell1997，88，2： | 1 |
| 8 | The evolving technology of DNA fingerprinting and its application to fisheries and aquaculture 显示文摘 | O' Reilly P T Wright J M | 1995 | Journal ofFish Biology1995，47，： | 1 |
| 9 | Being different: Relational demography and organizational attachment 显示文摘 | Tsui A S Egan T D O' Reilly C A | 1992 | Administrative Science Quarterly1992，37，4： | 1 |
| 10 | Talent identification and devel- opment in soccer显示文摘 | WILLIAMS A M REILLY T | 2000 | J Sports Sci2000，18，65： | 1 |
| 11 | In situ detection of inflammatory mediators in post mortem human brain tissue after traumatic injury显示文摘 | Frugier T Morganti-Kossmann MC Or reilly D | 2010 | J Neuro- trauma2010，27，3： | 1 |
| 12 | Endostatin: an endogenous inhibitor of angiogenesis and tumor growth显示文摘 | O'Reilly MS Bohem T Shing Y | 1997 | Cell1997，88，2： | 1 |
| 13 | Endostating: an endogenous inhibitor of angiogenesis and rumor growth显示文摘 | O'Reilly MS Bohem T Shing Y | 1997 | Cell1997，88，2： | 1 |
| 14 | Endostatin:an endogenous inhibitor ofangiogenesis and tumor growth显示文摘 | O'Reilly MS Boehm T Shing Y | | 0，，： | 1 |
| 15 | Endostatin:an endogenous inhibitor of angiogenesis and tumor growth显示文摘 | O'REILLY MS BOEHM T SHINE Y | 1997 | Cell1997，88，2： | 1 |
| 16 | Seasonal variations in health-related human physical activity显示文摘 | Reilly T Peiser B | 2006 | Sports Med2006，36，6： | 1 |
| 17 | Independence of force production by digits of the human hand显示文摘 | REILLY K T HAMMOND G R | 2000 | Neuroscience Letters2000，290，： | 1 |
| 18 | Measures of insulin resistance add incremental value to the clinical diagnosis of metabolic syndrome in association with coronary atherosclerosis显示文摘 | Reilly MP Wolfe ML Rhodes T | 2004 | Circulation2004，110，7： | 1 |
| 19 | A comparison of two spectral wave models in the Southern California Bight显示文摘 | O′Reilly W C Guza R T | | 0，，： | 1 |
| 20 | Endostatin:an endogenous inhibitor of angiogenesis and tumor growth显示文摘 | O’REILLY M S BOEHM T SHING Y | 1997 | Cell1997，88，2： | 1 |
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