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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 | Reversible middle cerbral artery occlusion without craniectomy in rats 显示文摘 | Longa EZ Weinetein PR Carson S | 1999 | Stroke1999，20，10： | 2 |
| 3 | Catting edge : estrogen drives expanision of CD4+CD25+ regulatory T cell compartment显示文摘 | Polanczyk MJ Carson BD Subramanian S | 2004 | J Immunol2004，173，4： | 1 |
| 4 | 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 |
| 5 | Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinasdmTOR inhibitor显示文摘 | Van Aller G S Carson J D Tang W | 2011 | Biochem Biophys Res Cornmun2011，406，2： | 1 |
| 6 | Red blood cell transfusion: a clinical practice guideline from the AABB 显示文摘 | Carson JL Grossman B J Kleinman S | 2012 | Ann Intern Med2012，157，： | 1 |
| 7 | Classification cri- teria for Sjogren5 s syndrome:a revised version of the Euro- pean criteria proposed by the American-European Consensus Group显示文摘 | VITALI C BOMBARDIERI S JONSSON R MOUTSOPOULOS HM ALEXANDER EL CARSONS SE | 2002 | Ann Rheum Dis2002，61，6： | 1 |
| 8 | Hyperbaric oxygen therapy for stroke: A systematic review of the evidence显示文摘 | Carson S McDonagh M Russman B | 2005 | Clin Rehabil2005，19，8： | 1 |
| 9 | Depression after Stroke and Lesion Location:A System Review显示文摘 | CARSON AJ MACHALE S ALLEN K | 2000 | Lancet (S0140-6736)2000，356，： | 1 |
| 10 | Control of IκBα Proteolysis by Site-specific Signal-induced Phosphorylation显示文摘 | Brown K Gerstberger S Carson L | 1995 | Science1995，267，： | 1 |
| 11 | 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 |
| 12 | The evidence for dietary prevention and treatment of cardiovascular disease 显示文摘 | van Horn L McCoin M Kris-Etherton P M Burke F Carson J A S Champagne C M | 2008 | Journal of the American Dietetic Association2008，108，： | 1 |
| 13 | Structural variation in the human genome显示文摘 | FEUK L CARSON A R Scherer S W | 2006 | Nat Rev Genet2006，7，2： | 1 |
| 14 | Control-pollinated seed orchards of best general combiners - a new strategy for radiata pine improvement显示文摘 | Carson S D | 1986 | Agronomy Society of New Zealand1986，5，： | 1 |
| 15 | Developing the VRML 97 International Standard 显示文摘 | CARSON G S PUK R F CAREY R | 1999 | IEEE Computer Graphics and Applications1999，，3： | 1 |
| 16 | Control of IκBa proteo-lysis by site-specific signal-induced phosphorylation显示文摘 | Brown K Gerstberger S Carson L | 1995 | Science1995，，： | 1 |
| 17 | Reversible middle cerebral artery occlusion without craniectomy in rats显示文摘 | Longa EZ Weinetein PR Carson S | 1999 | Stroke1999，20，10： | 1 |
| 18 | Reversible middle cerebralartery occlusion without craniectomy in rats显示文摘 | Longa EZ Weinstein PR Carson S | 1989 | Stroke1989，20，1： | 1 |
| 19 | Hyperbaric oxygen therapy for brain injury,cerebral palsy,and stroke显示文摘 | Mc Donagh M Carson S Ash J | 2003 | Evid Rep Technol Assess(Summ)2003，，85： | 1 |
| 20 | Red blood celltransfusion : a clinical practice guideline from the AABB 显示文摘 | Carson JL Grossman BJ Kleinman S | 2012 | Ann Intern Med2012，157，： | 1 |
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