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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 | Role of Bentonite in Prevention of T-2 Toxicosis in Rats显示文摘 | Carson M S Smith T K | 1983 | J Anim Sci1983，57，6： | 1 |
| 3 | Identification of the imprinted KLF14 transcription factor undergoing human-specific accelerated evolution显示文摘 | Parker-Katiraee L Carson AR Yamada T | 2007 | PLoS Genet2007，3，5： | 1 |
| 4 | Sequencing and Valuating Public Goods显示文摘 | Carson R T Flores N E Hanemann M | 1998 | Journal of Environmental Eeonomics and Management1998，，36： | 1 |
| 5 | Uncertainty,Opportunism and Governance:The Effects of Volatility and Ambiguity on Formal and Relational Contracting显示文摘 | CARSON S J MADHOK A WU T | 2006 | Academy of Management Journal2006，49，5： | 1 |
| 6 | Valuation of Tropical Rainforests:Philosophical and Practical Issues in the Use of of Contingent Valuation显示文摘 | Carson R T | | 0，，01： | 1 |
| 7 | A Method to Make Use of Thermal Infrared Temperature and NDVI Measurements to Infer Surface Soil Water Content and Fractional Vegetation Cover 显示文摘 | Carson T N Gillies R R Perry E M | 1994 | Remote Sensing Reviews1994，，9： | 1 |
| 8 | Mechanism of action of Melaleuca alternifolia(tea tree) oil on Staphylococcus aureus determined by time-kill,Lysis,leakage,and salt tolerance assays and electron microscopy显示文摘 | Carson C F Mee B J Riley T V | 2002 | Antimicrob Agents Chemother2002，46，6： | 1 |
| 9 | Valuation of tropical rainforests: philosophical and practical issues in the use of contingent valuation显示文摘 | CARSON R T | 1998 | Ecological Economics1998，24，： | 1 |
| 10 | Role of bentonite in prevention of T- 2 toxicosis in rats 显示文摘 | Carson M S T KSmith | 1983 | Journal of Animal Sci- ence1983，57，6： | 1 |
| 11 | The Importance of Storage, Transfer and Collection 显示文摘 | KNOWLTON T M CARSON J W KLINZING G E | 1994 | Chemical Engineering Progress1994，90，1： | 1 |
| 12 | Valuation of tropical rainforests: philosophical and practical issues in the use of contingent valuation显示文摘 | CARSON R T | 1998 | Ecological Economics1998，24，： | 1 |
| 13 | In vitro activity of Melaleuca alternifolia (tea tree) oil against dermatophytes and other filamentous fungi 显示文摘 | HAMMER K A CARSON C F RILEY T V | 2002 | Journal Antimicrobial Chemotherapy2002，50，2： | 1 |
| 14 | He- donic and Utilitarian Motivations for Online Re- tail Shopping Behavior 显示文摘 | Childers T L Carr C L Peck J Carson S | 2001 | Journal of Retai- ling2001，77，4： | 1 |
| 15 | Contingent Valuation and Revealed Preference Methodologies: Com- paring the Estimates for Quasi-public Goods 显示文摘 | Carson R T Flores N E Martin K M | 1996 | Land Economics1996，71，1： | 1 |
| 16 | Forcasting the path of China's CO2 emissions using province-level information 显示文摘 | Auffhammer M Carson T | 2008 | Journal of Environmental Economics and Management2008，55，： | 1 |
| 17 | Transcriptionalprofiles of intestinal tumors in Apc(Min)mice are uniquefrom those of embryonic intestine and identify novel gene tar-gets dysregulated in human colorectal tumors显示文摘 | Reichling T Goss KH Carson DJ | 2005 | CancerResearch2005，65，1： | 1 |
| 18 | 显示文摘 | CARSON R T VIGNALI D A | 1999 | Journal of Immunological Methods1999，227，： | 1 |
| 19 | The Viviparous-1 developmental gene of maize encodes a novel transcriptional acti- vator 显示文摘 | MCCARTY D R HATTORI T CARSON C B | 1991 | Cel11991，66，5： | 1 |
| 20 | Uncertainty, opportunism and governance : the effects of volatility and ambigu- ity on formal and relational contracting显示文摘 | Carson S J Madhok A Wu T | 2006 | Academy of Management Journal2006，49，： | 1 |
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